Despite the fact that substantial epidemiological evidence supports that histoplasma capsulatum is the causative agent of this syndrome [418], the etiology of OHS remains presumptive. It has been estimated that around 2,000 child and young adult will have considerable loss of vision every year in the United States secondary to choroidal neovascular membranes of POHS [419].

Histopathologically, histo spots and peripapillary lesions demonstrate chorioretinal scarring with a variable amount of lymphocytic infiltration. Symptomatic macular scars show a break in Bruch’s membrane with a choroidal neovascular membrane often extending into a disciform lesion [420].

16.7.1.2  Diagnosis and Treatment

The characteristic clinical picture with positive histoplasmin skin test aids in the diagnosis. Chest X-ray may reveal typical pulmonary lesions. Options for treatment of subretinal neovascular membranes related to ocular histoplasmosis include laser treatment in selected cases (extra foveal and juxtafoveal membranes) [421, 422], surgical removal of the membrane in selected cases [423], and photodynamic therapy [424].

The role of laser and surgical treatment in the management of choroidal neovascular membrane due to POHS is not clear. Conservative treatment with observation only resulted in involution of the membrane in a considerable number of cases [425]. Children and

young adults tend to have good prognosis, and conservative treatment may be warranted [419, 426].

16.7.2  Fungal Endophthalmitis

16.7.2.1  Endogenous Fungal Endophthalmitis

Fungi can cause endophthalmitis in a predisposed host. Exogenous fungal endophthalmitis occurs when the fungus is carried into the eye after penetrating trauma or surgery or may occur secondary to deep fungal keratitis. Endogenous endophthalmitis, on the other hand, occurs secondary to spread of the organism to the eye via the blood from remote sites. Intravenous injection using contaminated needles is another cause of endogenous fungal infection in drug addicts [427].

Multiple risk factors for development of fungemia are well known and include indwelling catheter use, parenteral drug abuse, parenteral hyperalimination, malignancy, corticosteroids and immunosuppressive therapy, surgical procedures (especially those of the gastrointestinal tract), prior antibiotic treatment, and prematurity [428–430]. Ocular candidiasis has been reported in patients after heart surgery [431] and after surgically induced abortion [432].

Candidiasis

Candida species are now the third most common nosocomial pathogen accounting for approximately 10% of

all hospital-acquired infections [433]. The incidence of ocular involvement in patients with candidemia is becoming less because of early diagnosis and more aggressive initial treatment [433]. Risk factors for development of candidemia are generally the same as for any fungemia. Candida is a common saprophyte of the gastrointestinal tract, genitourinary, and respiratory systems and can gain access to the body from these sites when risk factors exist.

Candida chorioretinitis is the most common intraocular fungal infection in infants, and the presence of ocular involvement in infants is highly suggestive of systemic candidiasis [434]. Risk factors for development of fungemia in infants include prolonged hospitalization, prolonged use of intravenous lines, use of multiple antibiotics, parenteral hyperalimination, gastrointestinal surgery, prematurity, and low birth weight. The immature immune system of infants is felt to make them more susceptible to infection [434–437].

Ocular Features

Ocular symptoms generally start to appear several days after the diagnosis of disseminated candidiasis has been established [438]. Symptoms in older children may include floaters and blurred vision. A painful red eye can be present at any age. Anterior segment examination may reveal flare, cells, and hypopyon. Iris abscess has been reported [439]. Posterior segment manifestations can be divided into 3 distinct categories [440]. Candida chorioretinitis with the presence of deep, white infiltrative chorioretinal lesions, and no evidence of direct vitreal involvement except for diffuse vitreous haze is a common presentation (Fig. 16.20). Candida endophthalmitis occurs when candida chorioretinitis lesions are seen extending into the vitreous or in the presence of vitreous abscess manifesting as intravitreal fungal balls. Finally, nonspecific fundus changes including hemorrhages, nerve fiber layer infarcts, and white-centered hemorrhages (Roth spots) may be seen.

The primary focus of infection is usually the choroid. When fungus is present in the retina, there is generally an evidence of inward spread from the nearby choroid. Microscopic examination of the lesion in candidiasis usually discloses yeast or pseudomycelium elements in the presence of suppurative inflammatory response.

Fig. 16.20  Infiltrative chorioretinal lesions secondary to candida endophthalmitis. (Photo courtesy of Peter Buch, University at Buffalo, Ross Eye Institute Buffalo, NY, USA)

Diagnosis and Treatment

Clinical appearance of the lesion in a predisposed child is generally highly characteristic and may be sufficient to prompt treatment. Positive cultures taken from the blood, urine, or any other body sources may be helpful in diagnosis since infection at these sites usually precedes ocular involvement. Vitrectomy and culture of the vitreous are not routinely needed unless the diagnosis is not clear.

The treatment of candida chorioretinitis is intravenous amphotericin B alone or in combination with 5-fluorocytocine or oral fluconazole. Whenever the vitreous is involved, intravitreal amphotericin B may be given with the systemic therapy. In young children, intravitreal injection of amphotericin B is usually not required unless the macula is involved. Antifungal treatment is usually effective with resolution of infection within days of starting treatment [441, 442].

Systemic amphotericin B is better tolerated in neonates than in older children or adults. The initial dose is 0.25–0.5 mg/kg and is increased by a similar amount on a daily basis until dosage of 1 mg/kg/day is reached. It is infused over 2–4 h. Side effects of amphotericin B in children and neonates include nephrotoxicity. Neonates do not experience fever, chills, or vomiting that is common in older individuals [443]. The dose of oral fluorocytosine in children is 100–150 mg/kg/day divided every 6 h. Side effects in children include hepatotoxicity, bone marrow suppression, gastrointestinal intolerance, and hemorrhagic enterocolitis [444, 445].