Ocular Pathology

Use it to review eye pathology for Ophthalmology Board Review or OKAP. Anatomy and pathology of the human eye. Included solar-lentigo, phakomatous choristoma (phacomatous-choristoma), congenital hereditary endothelial dystrophy, Fuch's dystrophy, bullous keratopathy, conjunctival nevus, syringoma, primary acquired melanosis,carcinoma-in-situ, BIGH3 dystrophy, and other lesions seen in eye-pathology. The cornea, iris, lens, sclera, retina and optic nerve are all seen.

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Saturday, March 10, 2007

Congenital Syphilitic Stromal Keratitis

Definition: Syphilitic stromal keratitis is a form of chronic stromal keratitis with vascularization. The term interstitial keratitis was coined in the 1800’s by Hutchinson for congenital syphilis and unfortunately (from the pathologists perspective) is still used.
Incidence/Prevalence: Syphilitic stromal keratitis is the most common manifestation of untreated late congenital syphilis; it occurs in about 20-50% of patients. The prevalence of syphilis is about 10-50 early cases per 100,000 in the U.S. population. At least 12 million cases of syphilis have been reported in adults annually in the world with estimates between 500,000- 1 million affected pregnancies. It has been estimated that about 40% of cases of untreated congenital syphilis will get syphilitic stromal keratitis.
Etiology: Transplacental infection of the fetus is produced by the spirochete, Treponema palladium. The late onset of congenital syphilitic keratitis is thought to be explained by an immune response to microbes or their antigens. Organisms have been identified in the aqueous of patients with congenital syphilis. [Ref 1&2]
Clinical Findings: The initial presentation of congenital syphilis (late untreated) has its onset between ages 5 and 20 as an acute stromal keratitis and iridocyclitis. 80% of cases are bilateral although the initial presentation involves first one eye followed in weeks to months by the fellow eye. Clinically, there are deep stromal chronic infiltrates and edema that may produce several patterns. Multifocal, sectoral, peripheral, punctate, linear, ring and deep infiltrates are all described. Vessels grow in toward the central deep cornea from the periphery. Scrolls of Descemet’s membrane produce the “glasleitern” which has a distinctive web-like clinical pattern.
Histopathology: The corneal stroma shows scarring at variable depths (numbers 1), deep stromal vascularization (arrow 2) and during the active phase intense lymphocytic inflammation. The histopathologic findings are frequently termed interstitial keratitis; the findings are similar to a scar after infection and are not specific for syphilis. However, about 88% of specimens may show a multi-lamellar intact Descemet’s membrane [Ref 3]. In the figure Descemet's membrane is folded and multilaminar (arrow 3). Scrolling of Descemet's membrane may also be seen. Secondary guttata are quite common (blue arrows ) but not specific .
Treatment: Penicillin and topical steroids may shorten the course of disease according to some authors while others suggest that the infants must be treated by 3 months of age in congenital syphilis to prevent the onset of keratitis.
Prognosis: Resolution occurs spontaneously after weeks to months. About 75% of patients will recover vision but if left untreated, stromal keratitis recurs in about 10% of patients albeit in a milder form. Ghost vessels may persist for years.

References:
1. Goldman J.N. and Girard KF. Intraocular treponemes in treated congenital syphilis, Arch Ophthalmol 78 (1967), pp. 47–50.
2. Smith J.L. and Israel C.W., The presence of spirochetes in late seronegative syphilis, JAMA 199 (1967), pp. 980–985
3. Waring et al. AJO 1976

Friday, March 02, 2007

Fungal Keratitis

Definition: Infection of the cornea caused by fungus.
Incidence/Prevalence: The incidence is less than 5% of corneal infections in the U.S. The most common organisms include Aspergillus, Candida, and Fusarium. There is a predilection for fungal keratitis for warmer humid climates. Aspergillus and Fusarium are more common in the southern U.S. Candida makes up a greater percentage of fungal keratitis in the northern U.S.
Etiology: Plant matter bearing fungus that penetrates the cornea (e.g. gardening) is a common source of fungal keratitis. Contact lens wear, use of topical steroids, cornea surgery, or keratitis from non-fungal causes are all risk factors. Candida is the most common cause of fungal keratitis. Paecilomyces lilacinus is known to contaminate intraocular lenses. Aspergillus is also a common source of fungal keratitis.
Clinical Findings: Patients may present with a dry fluffy infiltrate in the cornea with feathered margins that are usually white to gray in color. The lesions are usually slowly expansive and indolent and as it progresses to involve the deeper stroma. In the image one can compare the region of necrotizing keratitis (yellow arrow 1) to the relatively less involved cornea (yellow arrow 2) to see the dense white infiltrate that opacifies the cornea. The fungus has infiltrated and destroyed much of the deep stroma to involve the anterior chamber (#3 black arrow). A histologic section in the same area is shown below (black arrows). The initial signs of inflammation may be minimal but as the disease worsens so does the ocular injection.
Histopathology: The hallmark of fungal keratitis is the necrotizing keratitis (black arrow 1) that in general is associated with both an acute and granulomatous inflammatory infiltrate. Neutrophils (#3 black) as well as histiocytes and even multinucleated giant cells comprise the infiltrate. In the cornea there is often ulceration and a severe necrotizing stromal keratitis. In this setting special stains such as Grocott-Gomori methenamine-silver nitrate (GMS stained image #5), and periodic acid Schiff will often highlight the fungal elements. Fungus has penetrated to the anterior chamber (black arrow 5).
The high magnification image shows a fungus with hyphal structures that branch into 2 parts (dichotomous) at 45 degree angles (arrow 1). The hyphae are 'sepatated'. This is a section of Aspergillus.









In the image shown above, there is a large fungal mass that has infiltrated and replaced the necrotic cornea. Descemet's membrane may be seen at the bottom of this PAS stained slide. At higher magnification once sees a mass of pseudohyphae that are so dense that the branching pattern is difficult to discern but the fungal elements are clearly very strongly PAS positive.






















An image of a GMS stained section at the edge of the fungal mass shows budding yeast (red arrow 4). These 3 images depict Candida sp.
Fusarium (red arrow 1) is usually distinguished by its thin hyphae with very rare septae and a right angle branching pattern. Other fungal organisms, including Candida and organisms causing mucormycosis, are visible with routine H&E preparations, although better seen with special stains.
Treatment: Antifungal agents include polyenes, e.g. amphotericin and natamycin, that bind to ergosterol, a component of fungal cell walls, and disrupt the fungal cell wall. Imidazoles, such as ketoconazole, fluconazole interrupt ergosterol synthesis. Fluorinated pyrimidines, such as fluocytosine, work by selective transport mechanism involving a permease into the fungal cell and then blockage of thymidine synthesis.
Candida is often treated with topical amphotericin B (up to 0.3%). Flucytosine may be added and in severe cases oral fluconazole.
Aspergillus filamentary keratitis has been treated with topical amphotericin B, natamycin, as well as oral itraconazole, and ketoconazaole.
Fusarium has been treated with natamycin and ketoconazole.
Mechanical debridement has been used to try to improve penetration of the drug and often is done for diagnostic purposes initially.