Infectious Chorioretinal Diseases




Abstract


Infectious diseases affecting the retinochoroid can present with protean manifestations. A number of organisms such as bacteria, viruses, and fungi can affect the choroid and involve the outer retinal layers. Infectious chorioretinal diseases, particularly, are more common in developing countries and can often present as a diagnostic dilemma requiring detailed clinical and laboratory analysis. Often, laboratory assays of ocular fluids and/or tissues may be required to establish accurate diagnosis. These entities can present also with characteristic features on clinical examination and imaging evaluation that may provide clues that help in early diagnosis. In the past few years, there have been numerous reports in the literature that describe the use of modern imaging modalities such as enhanced-depth imaging optical coherence tomography and ultrawide field fundus photography in the characterization of these entities. In the index chapter, various infectious chorioretinal diseases such as tuberculosis and toxoplasmosis, to name a few, are described with an emphasis on their clinical and imaging features.




Keywords

Tuberculosis, Serpiginous-like choroiditis, Toxoplasmosis, Syphilis, Cat scratch disease, Lyme’s disease, Optical coherence tomography, Fluorescein angiography

 




Introduction


Severe visual loss may occur among patients with infectious posterior uveitis and chorioretinitis, especially if there is a delay in the diagnosis. A number of infectious agents can affect the retinochoroidal tissue resulting in intraocular inflammation. These include a host of bacteria, viruses, fungi, and parasites. Often, infectious chorioretinitis may mimic noninfectious inflammatory conditions leading to difficulties in diagnosis. Initiation of therapy with corticosteroids in such cases may result in worsening of the disease and can lead to sight-threatening sequelae. Although the ocular manifestations of infectious choroiditis depend upon the virulence of the organism, immunological response of the host plays an important role in pathogenesis of the disease. Such complex host and pathogen interplay may lead to development of characteristic disease phenotype, recognition of which is an important step in the diagnosis and management.


In the past decade, there have been numerous advances in the field of ocular imaging that have greatly enhanced our knowledge of disease pathogenesis. With the help of multimodal imaging techniques, staging, treatment response, and prognosis of various entities such as tubercular serpiginous-like choroiditis and toxoplasmosis can be accurately assessed. In the following sections, summary of various clinically relevant infectious entities presenting as chorioretinitis has been presented. This chapter also provides a comprehensive overview of imaging features for each of these conditions.




Introduction


Severe visual loss may occur among patients with infectious posterior uveitis and chorioretinitis, especially if there is a delay in the diagnosis. A number of infectious agents can affect the retinochoroidal tissue resulting in intraocular inflammation. These include a host of bacteria, viruses, fungi, and parasites. Often, infectious chorioretinitis may mimic noninfectious inflammatory conditions leading to difficulties in diagnosis. Initiation of therapy with corticosteroids in such cases may result in worsening of the disease and can lead to sight-threatening sequelae. Although the ocular manifestations of infectious choroiditis depend upon the virulence of the organism, immunological response of the host plays an important role in pathogenesis of the disease. Such complex host and pathogen interplay may lead to development of characteristic disease phenotype, recognition of which is an important step in the diagnosis and management.


In the past decade, there have been numerous advances in the field of ocular imaging that have greatly enhanced our knowledge of disease pathogenesis. With the help of multimodal imaging techniques, staging, treatment response, and prognosis of various entities such as tubercular serpiginous-like choroiditis and toxoplasmosis can be accurately assessed. In the following sections, summary of various clinically relevant infectious entities presenting as chorioretinitis has been presented. This chapter also provides a comprehensive overview of imaging features for each of these conditions.




Intraocular Tuberculosis


Tuberculosis (TB) is a leading infectious cause of morbidity and mortality and has been declared as a global emergency by the World Health Organization. Nearly one-third of the world’s population is infected by Mycobacterium tuberculosis , and 10% of these are likely to develop the disease at some time in their lives. TB primarily affects the lungs, though it may also affect extrapulmonary organs. Intraocular TB represents an extrapulmonary form of the disease. Ocular involvement has been reported in 1.4–6.8% of patients with pulmonary TB in different studies.


Due to the paucibacillary nature of the disease, obtaining microbiological confirmation of diagnosis in the form of smear positivity for acid fast bacilli or culture positivity is seldom possible from ocular fluids. Therefore, investigations that are conventionally used for diagnosing pulmonary TB are often unable to clinch a diagnosis of tubercular uveitis.


Clinical Spectrum


The choroid is the most commonly affected structure in intraocular TB. Posterior segment uveitis is the most common form of involvement. The posterior segment manifestations include the following:



  • 1.

    Multifocal choroidal tubercles


  • 2.

    Solitary choroidal tuberculoma


  • 3.

    Subretinal abscess


  • 4.

    Serpiginous-like choroiditis, neuroretinitis


  • 5.

    Retinal vasculitis


  • 6.

    Endophthalmitis and panophthalmitis



The following sections describe imaging characteristics of tubercular lesions that primarily involve the choroid.


Choroidal tubercles


Choroidal tubercles represent the most characteristic clinical presentation of ocular TB and occur as a result of hematogenous dissemination of tubercle bacilli from pulmonary and extrapulmonary sites. The tubercles may be unilateral or bilateral, usually multiple (≤5 in number), discreet grayish-white to yellowish subretinal lesions with indistinct borders ( Fig. 14.1 ). The lesions are usually seen in the posterior pole but may be present in the midperiphery as well. A choroidal granuloma may clinically resemble noninflammatory conditions such as central serous chorioretinopathy, choroidal metastases, melanoma of the choroid, and age-related macular degeneration.




Figure 14.1


Fundus photograph (A) and fluorescein angiogram (FA) (B–D) of a 18-year-old Asian Indian man showing presence of a choroidal tubercle near the inferotemporal arcade of the right eye. On FA, the early frame in the transit phase shows a well-defined hypofluorescence along with mild vascular leakage (B). In the successive frames (C and D), there is increasing hyperfluorescence and intense leakage in the area of choroidal tubercle.


Fluorescein Angiography and Indocyanine-Green Angiography


On fluorescein angiography (FA), choroidal tubercles are hypofluorescent in the dye transit and become hyperfluorescent in the late frames. On indocyanine-green angiography (ICGA), choroidal tubercles may have the following appearance: early and intermediate phase hypofluorescent lesions becoming hyperfluorescent in late phase (Type 1) indicating active choroidal lesions or remain hypofluorescent (Type 2) in the late phase indicating areas of atrophy. There may be presence of numerous hyperfluorescent spots, fuzzy appearance of choroidal vessels in the intermediate phase, and late choroidal hyperfluorescence due to dye leakage which tends to regress after completion of treatment with antitubercular therapy (ATT) and corticosteroids. The ICGA changes are reversible and may be used to monitor the response to therapy.


Optical Coherence Tomography


Optical coherence tomography (OCT) is useful in confirming the presence of exudative retinal detachment associated with choroidal granulomas. A characteristic appearance on OCT has been described in tubercular choroidal granuloma with an area of localized adhesion between the choriocapillaris-retinal pigment epithelial (RPE) layer and the overlying neurosensory retina. This has been termed “contact” sign and has been attributed to inflammatory adhesions overlying the granuloma. However, this sign may not pathognomic of choroidal tuberculous granuloma, and a similar appearance may be seen in other inflammatory granulomas. Nevertheless, OCT can play a role in the differentiating tuberculous choroidal granulomas from other noninflammatory lesions with a similar clinical picture. Enhanced-depth imaging OCT (EDI-OCT) scans have shown to display visible alterations in the choroid that coincide with the ICGA lesions in patients with choroidal granulomas. Invernizzi et al . showed that all choroidal granuloma lesions generated an increased transmission of the OCT signal toward the sclera. Compared with small lesions, large granulomas were more likely to be full thickness, round shaped, with defined margins, lower reflective than the surrounding structures and with a homogenous internal pattern. Granulomas in patients affected by TB-related uveitis were more likely to have a lobulated shape and nonhomogeneous internal pattern.


Studies have reported the use of swept-source OCT to study the choroidal and retinal anatomical sequelae in patients with choroidal granulomas of noninfectious etiology, for example, sarcoidosis. These are characterized by outer retinal tubulations and loss of normal choriocapillaris in the area of healed lesions. However, there are no published studies that have validated these findings among patients with tubercular choroidal granulomas.


Choroidal tuberculoma/subretinal abscess


A large, solitary choroidal granuloma may present as an elevated yellowish subretinal mass lesion often associated with exudative retinal detachment. The lesion is a result of rapid liquefaction caseation necrosis and tissue destruction. These patients often have disseminated systemic TB. The subretinal abscesses are more yellowish in color than a small choroidal granuloma, usually have overlying retinal hemorrhages, and have a tendency to develop retinal angiomatous proliferation over a period of time ( Fig. 14.2 ).




Figure 14.2


Ultrawide field fundus photography (A) of a 16-year-old man with a large subretinal abscess. The patient had a positive tuberculin skin test (30 × 30 mm; with ulceration) and mediastinal lymphadenopathy on contrast enhanced chest CT-scan. OCT shows presence of a large subretinal abscess with elevation of RPE (B). OCT B-scan passing through the macula shows presence of subretinal fluid. The patient was treated with antitubercular therapy along with corticosteroids.


Imaging Features


On B-scan ultrasonography, subretinal abscesses appear like an elevated mass lesion with high initial spike on A-scan and low internal reflectivity. These findings are common to elevated subretinal lesions of other uveitic etiologies as well. On FA, the lesions show early hypofluorescence and late hyperfluorescence. On ICGA, subretinal abscesses appear hypofluorescent throughout the early as well as late phase and larger in size than FA.


Serpiginous-like choroiditis


TB serpiginous-like choroiditis (TB SLC) typically affects young to middle-aged adults from TB-endemic areas. Unlike autoimmune serpiginous choroiditis, TB SLC occurs at a younger age, associated with mild vitritis and is bilateral in majority of the cases ( Fig. 14.3 ). It is thought to represent a hypersensitivity reaction to the tubercular bacilli sequestered in the RPE. This entity shows good response to combination treatment with corticosteroids and full course of antitubercular drugs.




Figure 14.3


Multimodal imaging of a 33-year-old woman with presumed tubercular serpiginous-like choroiditis with a strongly positive tuberculin skin test. Fundus photograph (A) shows characteristic yellowish choroiditis lesions with active fuzzy margins spreading in a serpentine manner. Fundus autofluorescence (B) shows presence of hyper-autofluorescence with hypo-autofluorescent edges within the lesion suggestive of activity. Combined fluorescein angiography (FA) and indocyanine green angiogram (ICGA) (only late frames shown) show late hyperfluorescence on FA and persistent hypofluorescence on ICGA. Enhanced-depth imaging optical coherence tomography (D) passing through the lesion shows presence of photoreceptor inner segment–outer segment disruption (yellow arrowheads) and thickening of the retinal pigment epithelium. There is evidence of choriocapillaris thickening and ischemia. Antitubercular therapy and corticosteroids were initiated for the patient.


TB SLC may have different morphological patterns:



  • 1.

    Multifocal discreet lesions, yellowish-white in color, measuring about 1/4 to 1 disk diameter in size with well-defined margins and slightly raised edges which are noncontiguous initially and show a wave-like progression over a period of 1–4 weeks and gradually become confluent. On FA, the lesions are hypofluorescent in the early phase with late hyperfluorescence. As the lesions become confluent, the advancing edge shows early hypofluorescence with late hyperfluorescence. On ICGA, the lesions remain hypofluorescence from early to late phase.


  • 2.

    A diffuse plaque-like lesion with an ameboid pattern and active serpiginous-like edge at the initial presentation. The edges are yellowish-white and elevated, whereas the center of the lesion is less elevated with pigmentary changes suggestive of a healing process in the center of the lesion. On FA, the center of the lesion shows mixed hyperfluorescence, whereas the advancing edge shows early hypofluorescence with late hyperfluorescence.


  • 3.

    Mixed pattern with overlapping features in opposite eyes.



Optical Coherence Tomography


Studies that have assessed spectral-domain OCT imaging among patients with TB SLC have described presence of retinal atrophy in the peripapillary region, disruption of the photoreceptor layer, thinning of RPE, mild cystic changes as well as subretinal fibrosis in area of old choroidal neovascularization, and marked attenuation of the interdigitation zone in the outer retina. Features observed on high-resolution spectral-domain OCT scans and correlation with simultaneous fundus autofluorescence (FAF) in eyes with TB SLC have been described.


Acute stage of SLC: OCT B-scans passing through the hyper-autofluorescent active edge of the lesion show a localized, fuzzy area of hyperreflectivity in the outer retinal layers involving the RPE, photoreceptor outer segment tips (POST), photoreceptor inner segment–outer segment (IS/OS) junction, external limiting membrane (ELM), and the outer nuclear layer with no increased backscattering from the inner choroid.


Early healing stage of SLC: In the early stage of healing, OCT B-scans passing through the hyper-autofluorescent central part of the lesion show disappearance of the hyperreflective fuzzy areas that are replaced by irregular, hyperreflective knobbly elevations of the outer retinal layers. The RPE, POST, IS/OS junction, and the ELM cannot be distinguished at this stage. There is an increased reflectance from the choroidal layers due to attenuating RPE–photoreceptor complex.


Late healing stage of SLC: As the lesions heal further over the next 3–6 months, they show stippled pattern of predominant hypo-autofluorescence. The corresponding OCT scans show loss of RPE, POST, IS/OS junction, ELM, and increased reflectance from the choroid persists.


EDI-OCT: Infiltration of the choroid, elevation of the RPE-Bruch’s membrane complex, and focal increase in choroidal thickness have been described in patients with active TB SLC. Retinal thinning and loss of the ELM, ellipsoid and interdigitation zones, loss of visible choroidal vasculature with enhanced choroidal signaling are the findings corresponding to the atrophic inactive areas.


Paradoxical Worsening in Tubercular Serpiginous-Like Choroiditis


Paradoxical worsening following initiation of ATT has been well documented in systemic TB, more so in extrapulmonary TB, including intracranial tuberculomas, tuberculous meningeal radiculitis, and tubercular lymphadenopathy, among others. The worsening of these lesions is believed to be mediated by the host’s immune system because of a combination of factors including enhanced delayed hypersensitivity of the host, decreased suppressor mechanisms, and increased exposure to the mycobacterial antigens or a response to mycobacterial antigens such as tuberculoproteins. Paradoxical worsening has been reported in 14% of patients of intraocular TB after 2–6 weeks of initiation of ATT. These patients should continue to receive ATT despite initial worsening as it helps in reducing the number of recurrences over a long-term follow-up. This phenomenon should not be mistaken for drug-resistant tubercular SLC or other possible nontubercular etiologies.


Role of Ultrawide Field Retinal Imaging in Detecting Paradoxical Worsening


The incidence of paradoxical worsening may be higher than previously reported. With the recent introduction of ultrawide field (UWF) retinal imaging, it is possible to simultaneously document central and peripheral TB SLC lesions in one image and monitor the overall response to treatment on successive visits. Therefore, it may be superior to the conventional imaging in identifying any peripheral paradoxical worsening which may otherwise get missed due to inability of conventional imaging to capture all lesions at every visit. The finding may affect management decisions such as increasing the dose of systemic immunosuppression.


Treatment


The treatment of ocular TB consists of standard four drug regimen of isoniazid (5 mg/kg/day), rifampicin (10 mg/kg/day), ethambutol (15 mg/kg/day), and pyrazinamide (20–25 mg/kg/day) along with pyridoxine (vitamin B6). Ethambutol and pyrazinamide are stopped after a period of 2 months. The role of ATT in intraocular TB is to eliminate the bacilli and reduce the antigen load, which may prevent recurrence of the disease. ATT is usually given in combination with systemic steroids (oral prednisolone 1 mg/kg/day) which are then tapered over the next 6–12 weeks depending upon the severity of inflammation. Topical steroids may be employed in cases with anterior segment inflammation. Systemic immunosuppressants and steroid sparing agents such as azathioprine may be added as and when required.




Toxoplasmosis


Toxoplasmosis is a systemic disease caused by the obligate intracellular protozoan parasite Toxoplasma gondii that affects both humans and animals. Members of the Felidae (cat) family serve as definitive hosts. Ocular toxoplasmosis is the leading cause of posterior uveitis in the world including northern Europe, North America, and South America. It accounts for about 30–50% of all cases of posterior uveitis. The estimated incidence of symptomatic active toxoplasma retinochoroiditis among people in London who were born in the United Kingdom is 0.4 cases/100,000 population/year. In the United States, the Centers for Disease Control and Prevention has estimated that 22.5% of the population who are 12 years and older have been infected with T. gondii and up to 10% of infected individuals present with retinal lesions. The risk of retinochoroiditis in adults with postnatally acquired infection varies from 2% in North Eastern Brazil to 25% in Southern Brazil.


Clinical Features


Ocular involvement can be a result of acquired infection or, more commonly, a recurrence of the congenital form of the disease. Ocular toxoplasmosis associated with congenital T. gondii infections can be apparent at birth, either as active retinal lesions or as healed retinochoroidal scars. Various clinical manifestations include the following:



  • 1.

    Retinochoroiditis


  • 2.

    Vasculitis


  • 3.

    Vascular occlusion


  • 4.

    Papillitis


  • 5.

    Neuroretinitis.



Classically, lesions of Toxoplasma retinochoroiditis appear as foci of inner retinitis adjacent to an old chorioretinal scar and are accompanied by dense focal vitritis ( headlight in fog appearance) ( Fig. 14.4 ). In primary acquired disease, the retinitis is seen without the presence of any previous scar. Recurrences manifest as satellite lesions at a border of preexisting retinochoroidal scars with variable pigmentation. However, in some patients, new primary retinal lesions (defined as those not arising from retinochoroidal scars can develop far away from the preexisting scars, in areas of retina that had appeared clinically normal) may occur. Recurrences are unpredictable and can occur months to years after the resolution of the primary lesion.




Figure 14.4


Fundus photographs of a 21-year-old man diagnosed with toxoplasmosis. At the initial visit (A), fundus photograph shows presence of dense vitritis, media haze, and a yellowish-white chorioretinal lesion in the posterior pole near the fovea. There are dense vitreous membranes and the lesion is surrounded by retinal edema. Following initiation of therapy, there was progressive decrease in vitreous inflammation, pigmentation of the lesion, and formation of a dense chorioretinal scar (B and C).


The typical lesion is a yellowish–whitish area of necrotizing retinitis with poorly defined margins due to surrounding edema. The lesion is frequently located in the macula or posterior to the equator but may occur in the periphery. The edges of the lesion gradually become well-defined, and the lesion progressively heals from periphery toward the center leaving behind a scar tissue. The scar gets progressively pigmented starting at the edges. The average time for the scarring of an active lesion often appears to be related to the lesion size and immune status of the host; resolution often occurs in approximately 3–4 weeks. With prompt diagnosis and treatment, lesions may resolve more rapidly. In an immunocompromised host, the disease may have bilateral presentation and multiple foci in one eye. The lesions tend to enlarge progressively resembling viral retinitis.


Three distinct morphologic forms of Toxoplasma lesions have been described:



  • 1.

    Large destructive lesions


  • 2.

    Punctate inner lesions


  • 3.

    Punctate outer lesions.



Vasculitis may be associated with the retinochoroiditis lesion ( Kyrieleis’ vasculitis ). Periphlebitis is more frequent than arteritis; retinal hemorrhages may also be seen. In some cases with very intense inflammation, vasculitis may be present in areas distant from the primary site of retinochoroiditis. Vein or retinal vascular occlusions may also occur as a complication of ocular toxoplasmosis. Papillitis, juxtapapillary chorioretinitis, and neuroretinitis are the less common clinical manifestations of ocular toxoplasmosis.


Fluorescein Angiography


Early phase of FA shows an area of hypofluorescence corresponding to active lesions of toxoplasmosis followed by hyperfluorescence progressing from the periphery of the lesion to its center. There is hyperfluorescence of the surrounding vessel walls suggestive of active vasculitis. Pigmented scars show areas of blocked fluorescence with staining of the scar tissue in late phase. Juxtapapillary cases show progressive hyperfluorescence of the disk. Cystoid macular edema may occur in posterior pole lesions or in cases with severe inflammation. Hypofluorescent areas corresponding to ischemia may be seen in cases associated with vascular occlusions. For cases with choroidal neovascularization associated with a previous healed scar, there is a typical pattern of early lacy hyperfluorescence with progressive late leakage.


Indocyanine-Green Angiography


ICGA appears useful in assessing the extent of choroidal involvement and the evolution of Toxoplasma lesions. Choroidal hypofluorescence is seen in the area of the main lesion and may extend further away from the lesion indicating that Toxoplasma retinochoroiditis is a more widespread process than is clinically suspected as it extends beyond the visible lesions. Multiple hypofluorescent dots described as satellite dark dots have been shown to be present away from the main area of hypofluorescence ( Fig. 14.5 ). These are present in areas that appear normal on clinical examination and FA and probably represent a perilesional inflammatory reaction. They have been reported to disappear following treatment.




Figure 14.5


Indocyanine-green angiography (ICGA), fluorescein angiography (FA), fundus autofluorescence (FAF), and enhanced-depth imaging optical coherence tomography (EDI-OCT) of a patient diagnosed with Toxoplasma retinochoroiditis. At the initial visit (A), ICGA shows a large area of hypofluorescence corresponding to the area of chorioretinal involvement. EDI-OCT B-scan passing through the lesion shows presence of a large subretinal lesion with disruption of inner retinal layers. After 8 weeks, ICGA shows decrease in the size of hypofluorescent area. Corresponding EDI-OCT B-scan shows resolution of choroidal inflammation and formation of a scar with chorioretinal disruption (B). FAF at the initial visit shows hypo-autofluorescence corresponding to the lesion (C). FA performed at the time of initial presentation shows early hypofluorescence (D) with late leakage (E). There is evidence of mild retinal vasculitis.


Optical Coherence Tomography


Spectral-domain OCT may be helpful in identifying the features, extent, and location of retinitis caused by toxoplasmosis and may be helpful in the visualization of the toxoplasmosis cyst or granuloma ( Fig. 14.5 ). In addition, OCT could be helpful in observing the progression of the disease and development of complications and provides information regarding the visual prognosis ( Fig. 14.6 ).




Figure 14.6


Multimodal imaging of a healed lesion of Toxoplasma retinochoroiditis. Fluorescein angiogram shows early hypofluorescence (A) followed by late staining (B). Infrared image (C) shows presence of a hyperreflectivity in the area of the lesion. Loss of retinal pigment epithelium (RPE) gives rise to hypo-autofluorescence on fundus autofluorescence imaging (D). Indocyanine-green angiography (E) shows presence of well-defined hypofluorescence in the area of the lesion. On enhanced-depth imaging optical coherence tomography (F), there are inner retinal atrophy, loss of RPE, and disruption of choroidal anatomy.


Active lesion: Active lesions of chorioretinitis show thickening and hyperreflectivity of the neurosensory retina, disruption of the photoreceptor IS/OS junction, choroidal shadowing, and elevation of the RPE ( Fig. 14.5 ). Choroidal thickening may occur beneath the active lesion in the acute phase, which subsequently returns to normal values as the inflammation resolves. It is also useful to detect subtle serous retinal detachment triggered by active retinochoroiditis or to detect subretinal new vessel formation.


Healed lesion: OCT through the site of healed lesion demonstrates thinning of the neurosensory retina, and disorganization of photoreceptor and RPE layer. Disruption of the photoreceptor layer can be helpful in predicting the visual prognosis ( Fig. 14.6 ).


Alwassia et al . have described sequential OCT findings in a case of toxoplasma retinochoroiditis with the following stages:



  • 1.

    Initial OCT scan showing a hyperreflectivity in the inner retinal layers with mild elevation representing the area of retinitis.


  • 2.

    Disruption in the IS/OS junctions of the photoreceptors.


  • 3.

    Early cystic changes in the inner nuclear layer.


  • 4.

    Discrete cyst in the ganglion cell layer, possibly representing toxoplasmosis tissue cyst (bradyzoite).


  • 5.

    Hyporeflective cystic changes, on follow-up scans, in the previous area of retinitis with greater disruption in the photoreceptor layer and marked loss of retinal tissue and distortion of the outer retinal architecture. The development of these cystic spaces may possibly represent progression from retinitis to liquefactive necrosis.


  • 6.

    As the healing progresses, the gap within the retina caused by necrosis becomes smaller with improvement in the architecture of inner and outer retinal layers.



Treatment


The most commonly employed treatment strategy for acute Toxoplasma retinochoroiditis is systemic administration of one or more antibiotics usually given for 4–8 weeks. Most agents are effective only against the active tachyzoite form of toxoplasma, and not the tissue-encysted bradyzoite form. The term, classic therapy or triple-drug therapy , refers to the combination of pyrimethamine (25–50 mg daily orally in one to two doses) and sulfadiazine along with corticosteroids and folinic acid. An alternative to classic treatment, trimethoprim–sulfamethoxazole (160–800 mg twice daily orally) is an attractive option for reasons that include low cost, wide availability, and tolerability though sulfonamide-related reactions may occur. This drug combination has a similar mode of action to pyrimethamine and sulfadiazine on tetrahydrofolate synthesis. Studies have indicated that trimethoprim/sulfamethoxazole/prednisone is an acceptable alternative to classic therapy. This combination may also have a role in the prevention of recurrent attacks of ocular toxoplasmosis. Clindamycin (300 mg orally four times daily) is a lincosamide antibiotic that interferes with translation of the apicoplast, which is an unusual plastid-like organelle found in T. gondii . The drug is often added to triple therapy, which is then referred to as “quadruple therapy.”


In conclusion, despite the common practice of treating Toxoplasma retinochoroiditis with systemic antibiotics, there are no randomized controlled trials demonstrating that antibiotic treatment improves long-term visual outcomes. Also, there is no convincing evidence to date that treatment decreases the severity of intraocular inflammation or duration of disease for all patients.




Ocular Syphilis


Syphilis is a multisystemic infection caused by the spirochete Treponema pallidum . Since the introduction of antibiotics, notably penicillin, the incidence of syphilis decreased dramatically to reach its lowest recorded level in the year 2000. The number of cases has steadily been rising, especially in developed countries like USA with a high rate of HIV coinfection ranging from 20% to 70%. Ocular syphilis is most commonly associated with secondary and tertiary syphilis and may be the presenting sign of the disease. However, latent and congenital infections may also be associated with syphilitic uveitis. Ocular involvement occurs in 4.6% of patients with secondary syphilis, typically after resolution of other signs of secondary syphilis. It varies widely in presentation; one or both eyes may be affected, and it can involve most parts of the eye from the conjunctiva to the extraocular cranial nerve. The prevalence of syphilis among patients presenting to uveitis referral centers has been estimated to be between 1% and 8%.


Clinical Features


Syphilitic uveitis can present as a nonspecific anterior, intermediate, posterior, or panuveitis ( great masquerader ). Uveitis in either the anterior or posterior segment is the most common presentation and can occur as early as 6 weeks after initial infection. Posterior uveitis may manifest as the following:



  • 1.

    Focal/multifocal chorioretinitis


  • 2.

    Acute posterior placoid chorioretinitis


  • 3.

    Necrotizing retinitis and retinal vasculitis similar to acute retinal necrosis (ARN)


  • 4.

    Intermediate uveitis


  • 5.

    Panuveitis.



Focal/multifocal chorioretinitis: The manifestation presents as a deep-yellow-gray lesion often with a shallow serous retinal detachment and overlying vitreous inflammation. Patchy diffuse chorioretinitis with vitritis is the most common manifestation and may involve retinal hemorrhages, perivasculitis, or other manifestations of retinal vasculitis. On FA, the lesions show early hypofluorescence followed by late staining.


Posterior placoid chorioretinitis: Acute syphilitic posterior placoid chorioretinitis is an uncommon but clinically distinct manifestation of ocular syphilis. It is characterized by pale-yellowish, ill-defined, solitary, placoid subretinal lesion in the posterior pole, or midperiphery of the fundus ( Fig. 14.7 ). These lesions usually have a faded center and stippled hyperpigmentation of the RPE, and they can coalesce to become large confluent lesions. Chorioretinitis is accompanied by variable amount of vitreous inflammation and may be associated with superficial hemorrhages, retinal vasculitis, disk edema, and serous detachment of the RPE. Retinal hemorrhages and vasculitis are typically observed among the immunocompromised patients. The clinical manifestations of acute syphilitic posterior placoid chorioretinitis strongly suggest active inflammation involving the choriocapillaris-pigment epithelium retinal receptor complexes.




Figure 14.7


Multimodal imaging of a 33-year-old patient diagnosed with acute syphilitic posterior placoid chorioretinitis. Fundus photograph shows presence of a large, yellowish, ill-defined, placoid subretinal lesion involving the posterior pole (A) and extending into the temporal periphery (B). Fundus autofluorescence (B) shows a typical stippled, variable hyper-autofluorescence in the region corresponding to the lesion. Indocyanine-green angiography (D) shows presence of hypofluorescence in the superior part of the lesion. Fluorescein angiography (early and late frames; E and F) shows a typical stippled pattern of hyperfluorescence (leopard spots).


Fluorescein Angiography and Indocyanine-Green Angiography


On FA, lesions of posterior placoid chorioretinitis show early central hypofluorescence followed by progressive hyperfluorescence in the area of the lesion. Variable or punctate hypofluorescence producing a classic “leopard spot” pattern may be seen in later stages. ICGA shows variable hypofluorescence in both early and late stages. FAF shows geographic pattern of hyper-autofluorescence corresponding to the lesion ( Fig. 14.7 ).


Optical Coherence Tomography


Several studies have described the OCT features of acute syphilitic posterior placoid chorioretinitis:



  • 1.

    Baseline OCT (performed within 1–2 days of presentation) may reveal a small amount of subretinal fluid, an intact ELM, disruption of the photoreceptor IS/OS junction, and thickening and granular hyperreflectivity of the RPE but without nodular elevations ( Fig. 14.8 ).




    Figure 14.8


    Enhanced-depth imaging optical coherence tomography (EDI-OCT) scans of a patient with acute syphilitic posterior placoid chorioretinitis shows presence of outer retinal deposits in the region of the retinal pigment epithelium (yellow arrows) (A). The placoid lesion is characterized by loss of photoreceptor inner segment–outer segment junction (yellow arrowheads) (B, C, and D).


  • 2.

    Subsequent OCT (7–10 days after presentation) may not show any evidence of subretinal fluid, but the scans show an irregular thickening and hyperreflectivity of the RPE with prominent nodular elevations, along with a loss of IS/OS and OS-RPE bands, and areas of punctate hyperreflectivity in the choroid.



Necrotizing retinitis: This form of syphilitic retinitis presents as single or multiple yellowish-white patches of necrosis often associated with vasculitis, vitreous inflammation, and varying degrees of anterior segment inflammation.


Treatment


The treatment of ocular syphilis resembles that of neurosyphilis. Aqueous penicillin G (18–24 million units/day intravenous for 10–14 days) in combination with probenecid (500 mg four times a day orally) are preferred for ocular syphilis, since these agents can cross the blood-ocular-barrier. Alternatively, ceftriaxone (2 g/day intravenous for 10–14 days) can be employed for patients with penicillin allergy. Topical steroids can be used for anterior segment inflammation and keratitis. Systemic steroids may be used for posterior uveitis with significant intraocular inflammation.




Introduction


Severe visual loss may occur among patients with infectious posterior uveitis and chorioretinitis, especially if there is a delay in the diagnosis. A number of infectious agents can affect the retinochoroidal tissue resulting in intraocular inflammation. These include a host of bacteria, viruses, fungi, and parasites. Often, infectious chorioretinitis may mimic noninfectious inflammatory conditions leading to difficulties in diagnosis. Initiation of therapy with corticosteroids in such cases may result in worsening of the disease and can lead to sight-threatening sequelae. Although the ocular manifestations of infectious choroiditis depend upon the virulence of the organism, immunological response of the host plays an important role in pathogenesis of the disease. Such complex host and pathogen interplay may lead to development of characteristic disease phenotype, recognition of which is an important step in the diagnosis and management.


In the past decade, there have been numerous advances in the field of ocular imaging that have greatly enhanced our knowledge of disease pathogenesis. With the help of multimodal imaging techniques, staging, treatment response, and prognosis of various entities such as tubercular serpiginous-like choroiditis and toxoplasmosis can be accurately assessed. In the following sections, summary of various clinically relevant infectious entities presenting as chorioretinitis has been presented. This chapter also provides a comprehensive overview of imaging features for each of these conditions.




Intraocular Tuberculosis


Tuberculosis (TB) is a leading infectious cause of morbidity and mortality and has been declared as a global emergency by the World Health Organization. Nearly one-third of the world’s population is infected by Mycobacterium tuberculosis , and 10% of these are likely to develop the disease at some time in their lives. TB primarily affects the lungs, though it may also affect extrapulmonary organs. Intraocular TB represents an extrapulmonary form of the disease. Ocular involvement has been reported in 1.4–6.8% of patients with pulmonary TB in different studies.


Due to the paucibacillary nature of the disease, obtaining microbiological confirmation of diagnosis in the form of smear positivity for acid fast bacilli or culture positivity is seldom possible from ocular fluids. Therefore, investigations that are conventionally used for diagnosing pulmonary TB are often unable to clinch a diagnosis of tubercular uveitis.


Clinical Spectrum


The choroid is the most commonly affected structure in intraocular TB. Posterior segment uveitis is the most common form of involvement. The posterior segment manifestations include the following:



  • 1.

    Multifocal choroidal tubercles


  • 2.

    Solitary choroidal tuberculoma


  • 3.

    Subretinal abscess


  • 4.

    Serpiginous-like choroiditis, neuroretinitis


  • 5.

    Retinal vasculitis


  • 6.

    Endophthalmitis and panophthalmitis



The following sections describe imaging characteristics of tubercular lesions that primarily involve the choroid.


Choroidal tubercles


Choroidal tubercles represent the most characteristic clinical presentation of ocular TB and occur as a result of hematogenous dissemination of tubercle bacilli from pulmonary and extrapulmonary sites. The tubercles may be unilateral or bilateral, usually multiple (≤5 in number), discreet grayish-white to yellowish subretinal lesions with indistinct borders ( Fig. 14.1 ). The lesions are usually seen in the posterior pole but may be present in the midperiphery as well. A choroidal granuloma may clinically resemble noninflammatory conditions such as central serous chorioretinopathy, choroidal metastases, melanoma of the choroid, and age-related macular degeneration.




Figure 14.1


Fundus photograph (A) and fluorescein angiogram (FA) (B–D) of a 18-year-old Asian Indian man showing presence of a choroidal tubercle near the inferotemporal arcade of the right eye. On FA, the early frame in the transit phase shows a well-defined hypofluorescence along with mild vascular leakage (B). In the successive frames (C and D), there is increasing hyperfluorescence and intense leakage in the area of choroidal tubercle.


Fluorescein Angiography and Indocyanine-Green Angiography


On fluorescein angiography (FA), choroidal tubercles are hypofluorescent in the dye transit and become hyperfluorescent in the late frames. On indocyanine-green angiography (ICGA), choroidal tubercles may have the following appearance: early and intermediate phase hypofluorescent lesions becoming hyperfluorescent in late phase (Type 1) indicating active choroidal lesions or remain hypofluorescent (Type 2) in the late phase indicating areas of atrophy. There may be presence of numerous hyperfluorescent spots, fuzzy appearance of choroidal vessels in the intermediate phase, and late choroidal hyperfluorescence due to dye leakage which tends to regress after completion of treatment with antitubercular therapy (ATT) and corticosteroids. The ICGA changes are reversible and may be used to monitor the response to therapy.


Optical Coherence Tomography


Optical coherence tomography (OCT) is useful in confirming the presence of exudative retinal detachment associated with choroidal granulomas. A characteristic appearance on OCT has been described in tubercular choroidal granuloma with an area of localized adhesion between the choriocapillaris-retinal pigment epithelial (RPE) layer and the overlying neurosensory retina. This has been termed “contact” sign and has been attributed to inflammatory adhesions overlying the granuloma. However, this sign may not pathognomic of choroidal tuberculous granuloma, and a similar appearance may be seen in other inflammatory granulomas. Nevertheless, OCT can play a role in the differentiating tuberculous choroidal granulomas from other noninflammatory lesions with a similar clinical picture. Enhanced-depth imaging OCT (EDI-OCT) scans have shown to display visible alterations in the choroid that coincide with the ICGA lesions in patients with choroidal granulomas. Invernizzi et al . showed that all choroidal granuloma lesions generated an increased transmission of the OCT signal toward the sclera. Compared with small lesions, large granulomas were more likely to be full thickness, round shaped, with defined margins, lower reflective than the surrounding structures and with a homogenous internal pattern. Granulomas in patients affected by TB-related uveitis were more likely to have a lobulated shape and nonhomogeneous internal pattern.


Studies have reported the use of swept-source OCT to study the choroidal and retinal anatomical sequelae in patients with choroidal granulomas of noninfectious etiology, for example, sarcoidosis. These are characterized by outer retinal tubulations and loss of normal choriocapillaris in the area of healed lesions. However, there are no published studies that have validated these findings among patients with tubercular choroidal granulomas.


Choroidal tuberculoma/subretinal abscess


A large, solitary choroidal granuloma may present as an elevated yellowish subretinal mass lesion often associated with exudative retinal detachment. The lesion is a result of rapid liquefaction caseation necrosis and tissue destruction. These patients often have disseminated systemic TB. The subretinal abscesses are more yellowish in color than a small choroidal granuloma, usually have overlying retinal hemorrhages, and have a tendency to develop retinal angiomatous proliferation over a period of time ( Fig. 14.2 ).


Sep 8, 2018 | Posted by in OPHTHALMOLOGY | Comments Off on Infectious Chorioretinal Diseases

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