The Inflamed Eye and Retinal Disease

Infectious Uveitis

ALI DJALILIAN AND ERIC SUHLER

Acquired toxoplasmosis in the non-immune-compromised adult is frequently asymptomatic. The most common manifestation is lymphadenopathy (90%) followed by fever, malaise, and sore throat. More severe disease can occur, affecting muscle, skin, brain, heart, and kidney. In the immunocompromised host, in particular acquired immunodeficiency syndrome (AIDS) patients, the disease can be a fulminant central nervous system disease that rapidly leads to death.

FIGURE 18–1. An old pigmented scar with an adjacent more active lesion in a patient with ocular toxoplasmosis.

In cases where the vitreous haze and cellular reaction are profound, patients become symptomatic. The most common symptoms are blurriness and floaters. Rarely, if the lesions involve the macula, optic nerve, or the vascular arcades, the patient can experience profound loss of vision.

The diagnosis of ocular toxoplasmosis is primarily clinical and is based on the typical ocular features. Serologic evidence of Toxoplasma infection is important to document exposure to the organism. The presence of IgG antibody at any titer even in undiluted serum (1:1) is considered positive. IgM antibodies suggest recent infection. A negative titer is evidence against the diagnosis and should alert the physician to other diagnoses. The type of serologic testing that is most reliable is still debatable, although the enzyme-linked immunosorbent assay (ELISA) is recommended by many. The Sabin-Feldman dye test requires live organisms and is used less frequently. It is important to realize that a positive antibody titer, which may be seen in nearly half of all adults, only indicates previous exposure and should be interpreted based on other clinical findings. Serologic examination of the aqueous or detection of the Toxoplasm a DNA by polymerase chain reaction (PCR) also has been used to determine specifically ocular infection in patients with positive serum antibodies.

The differential diagnosis includes other causes of infectious retinitis, such as tuberculosis, toxocara, syphilis, cytomegalovirus, Candida organisms, and herpes simplex. Other causes of uveitis, such as sarcoidosis, also may manifest in a similar fashion. All patients with suspected ocular toxoplasmosis should also have their human immunodeficiency virus (HIV) status determined. If the patient is HIV positive, an evaluation of the central nervous system is mandatory.

Several regimens can be used to treat ocular toxoplasmosis. The most common drug combination is sulfadiazine (1 g orally four times daily), pyrimethamine (50-mg load, then 25 mg orally once or twice a day) given concomitantly with folinic acid (leucovorin) 5 mg orally three times a week. A baseline blood count and platelet count should be obtained and repeated on a weekly basis while the patient receives pyrimethamine. Prednisone is judiciously added at a dose of 20 to 40 mg per day, beginning 12 to 24 hours after initiating specific antimicrobial therapy. Corticosteroids never are prescribed alone and never are administered by periocular injection. Topical corticosteroids and cycloplegics are used adjunctively in patients with anterior chamber reaction.

Alternative regimens include clindamycin (150 to 300 mg orally three to four times daily) combined with sulfasalazine. Psuedomembranous colitis is a concern with clindamycin use. Trimethoprim-sulfamethoxazole (one double-strength twice daily) also has been used with success. Likewise, azithromycin (250 mg daily) has been used successfully. Most recently, atovaquone (Mepron) has been used at a dose of 750 mg four times a day. In all regimens, systemic treatment typically is given for 3 to 6 weeks.

It is important to realize that all these regimens are targeting the tachyzoites (the active infectious form) and generally do not affect the tissue cyst. Although atovaquone has proven to be cysticidal in vitro, it remains to be seen clinically whether it can eradicate the organism. Therefore, toxoplasmosis can recur even after treatment because the tissue cysts generally survive. In patients with multiple recurrences, long-term prophylactic therapy with the preceding agents may reduce the likelihood of reactivation.

Infectious endophthalmitis can be divided into exogenous and endogenous types. In exogenous infections, the organism enters the eye from the external environment. The subtypes of exogenous endophthalmitis include postoperative, traumatic, and bleb-associated. In endogenous endophthalmitis, the organism reaches the eye through the vascular system.

Besides the clinical features, the diagnosis is primarily based on culture data. In case of P. acnes, it is important to inform the microbiology laboratory not to discard the cultures after the usual 3 to 4 days. Because the organism is slow growing, cultures should be maintained for 14 days.

Chronic postoperative endophthalmitis caused by S. epidermidis can be treated successfully with intravitreal injection of vancomycin. Therapy for P. acnes endophthalmitis usually involves a combination of vitrectomy, posterior capsulectomy, and intravitreal vancomycin. Although the intraocular lens does not need to be removed at the time of initial therapy, recurrent cases are managed with repeat intravitreal antibiotics and removal of residual posterior capsule and intraocular lens. The treatment for fungal endophthalmitis is discussed later herein.

For exogenous infections that are limited to the eye, vitrectomy combined with intravitreal amphotericin B is the mainstay of therapy. Oral fluconazole or ketoconazole also may be beneficial. Endogenous endophthalmitis requires systemic amphotericin B along with intravitreal amphotericin B.

Posttraumatic endophthalmitis can develop after penetrating injuries. The most common organisms are S. epidermidis, Bacillus cereus, S. aureus, and fungi. Endophthalmitis due to B. cereus characteristically has a very fulminant course with rapid progression.

Infection after filtering surgery is one of the morbidities associated with this procedure. The use of antifibrotic agents, the presence of bleb leaks, and the inferior location of the bleb are among the main risk factors for developing endophthalmitis. Typically, these infections occur late and are preceded by conjunctival injection and discharge. The most common organisms are Streptococcus species (including pneumococcus) and Haemophilus influenza. Treatment includes vitreous cultures, intravitreal antibiotics, and vitrectomy for the more severe cases.

Cytomegalovirus (CMV) is a double-stranded DNA virus in the herpes class that causes an asymptomatic or mononucleosis-like syndrome in healthy adults. More than half of all adults have evidence of previous CMV infection. CMV infection of the retina occurs as an opportunistic infection only in immunosuppressed persons or in infants with congenital infection. In the past, chemotherapy and organ transplantation, particularly of the kidneys, were the most common causes of CMV retinitis. In the current era, however, AIDS has led to a significant rise in the number of cases of CMV retinitis. Most recently, the number of new cases of CMV retinitis has declined significantly with the introduction of highly active antiretroviral therapy (HAART).

A combination of several antiretroviral agents, HAART has been highly effective in reducing the number of HIV particles in the bloodstream (as measured by the viral load) and more importantly in increasing the CD4-positive T-lymphocyte count. The typical regimen involves one protease inhibitor and two nucleoside reverse transcriptase inhibitors.

Cytomegalovirus retinitis progresses in two ways. New lesions may form that are not physically near an old lesion, probably by hematogenous spread. Second, and most common, an old lesion spreads at its borders to involve a new, previously uninfected retina. The rate of progression is approximately 250 μ per week. In assessing the progression of CMV retinitis, it is important to pay attention to the border of the lesion and look for advancement or new lesions. Clearing at the center of the lesion should not be interpreted as improvement because the whiteness will gradually decrease as the retina becomes atrophic.

Visual loss from CMV retinitis may occur in several ways. Most commonly, the infected retina develops an absolute scotoma due to retinal necrosis. As the macula is involved, the central vision is lost. In some patients, paramacular CMV will produce macular edema, which is a reversible cause of visual loss if it can be treated before the active virus progresses through the fovea. The optic disc can also be involved with severe loss of vision. Last, the retina can develop a rhegmatogenous retinal detachment because there is vitreous traction on the thin, atrophic retina.

Retinal detachment develops in about 20% of patients with retinitis; 50% of these patients develop detachment in the second eye if there is retinitis. The greater the degree of peripheral retinal involvement, the greater the risk of retinal detachment. The mechanism of detachment in CMV retinitis is vitreous traction on the thinned, atrophic retina. Multiple retinal breaks are usually present, and large relatively posterior breaks can be seen.

The surgical treatment can be challenging. Scleral buckling is appropriate when the breaks are located near the vitreous base. In CMV retinitis, however, these breaks tend to be more posterior. A more effective approach is vitrectomy, endolaser, and the use of a long-lasting retinal tamponade, namely, silicone oil. Silicone oil significantly reduces the risk of redetachment. The silicone oil typically is left in place as long as the patient is at risk for CMV.

Laser also has been used to demarcate areas of retinitis and thereby prevent detachment. This approach is not uniformly successful, and the retinitis can progress through the laser burns.

The most important and effective treatment for the long-term control of CMV retinitis is appropriate anti-retroviral therapy, which can increase the number of circulating CD4 cells and allow the patient’s own immune system to contain CMV. For the acute treatment of CMV retinitis, however, numerous of medications are available.

Oral ganciclovir, which has a low bioavailability, can be used for maintenance therapy as an alternative to intravenous ganciclovir. The typical dose is 3 to 6 g per day. The main advantage of oral administration is that it eliminates the need for long-term intravenous catheter and related complications.