Superior Limbic Keratoconjunctivitis

Definition: SLK is a bilateral chronic recurrent inflammatory lesion located in the superior bulbar and tarsal conjunctiva.
Etiology: SLK is often associated with thyroid dysfunction. One theory is that lid retraction results in rubbing of the tarsus and bulbar conjunctiva producing inflammation.
Epidemiology: Most common in adult women 20-70 years old.
Clinical: A bilateral and localized process confined to the superior limbal area and tarsus from the 10-2 o'clock position. Thickening of the conjunctiva accompanies dilated blood vessels and erythema of the conjunctiva. Both Rose Bengal and fluorescein stain in this region. Clinically these cases are often associated with dysthyroid eye disease that features lid retraction. In general thyroid function tests are recommended in patients that present with these findings.
Histopathology: Click to enlarge photo.

Superior limbic keratoconjunctivitis has been described as having keratinization of the epithelium (see the keratohyaline granules and anucleate squamous cells here) , acanthosis (notice the thickening to the far right), and cellular infiltration with lymphocytes, plasma cells and ballooning degeneration (see central cystic space with degeneration of epithelial cells and exocytosis of lymphocytes). In addition in this photo there is a chronic perivascular inflammatory infiltrate.

Treatment: SLK often spontaneously resolves but may recur for 10 years. Some treatments that have been used include bandage contact lenses, punctal occlusion, topical cyclosporin A (0.5%), topical application of autologous serum, thermo and chemical cauterization of the area affected , and resection of the conjunctiva.

Solar Lentigo

The differential diagnosis of lentiginous lesions can be challenging. It has been written that solar lentigo is the nascent lesion for seborrheic keratosis. Solar-lentigo generally features compact orthokerotosis with little melanin in the keratin layer (arrow 2), epidermal hyperplasia with bulbous rete ridges, pigmented keratinocytes especially prominent at the bulbs of the rete ridges (arrows 1). Melanocytes are generally not found in the epidermis (the absence of melanocytic hyperplasia is a key feature in this entity). Mild chronic inflammation may be present but often without pigment laden macrophages in the dermis. Lamellar collagen around the rete pegs is absent. While key features exist, the lack of melanocytic hyperplasia, the presence of bulbous tips, but also in contrast to some writings, there are numerous pigmented melanophages that are perivascular.

What is your diagnosis

Congenital Hereditary Endothelial Dystrophy

Definition: Two forms of CHED causing bilateral congenital corneal edema are described: autosomal recessive and autosomal dominant. The more common autosomal recessive form is present at birth, remains stable, and is accompanied by nystagmus.
Incidence/Prevalence:
Etiology: Originally, 7 different mutations have been identified in 10 families within the SLC4A11 gene in patients with AR CHED. The mutations involve a gene that encodes a membrane-bound sodium-borate cotransporter, and cause loss of function of the protein either by blocking its membrane targeting or perhaps nonsense-mediated decay. (1) As of 11/25/2007 30 different mutations have been identified in the SLC4A11 gene.
Clinical Findings: Clinically CHED shows a diffuse ground glass opacity of the cornea that is bilateral and progressive. There are 2 modes of inheritance that are reported. In the autosomal recessive form, edema appears within the neonatal period (sometimes at birth) and is associated with nystagmus. In the autosomal dominant form the cornea is clear at birth and the clouding progresses slowly usually at 1-2 years of age; nystagmus does not develop. There are no guttata here, distinguishing it from Fuch's dystrophy. Both forms have a similar clinical appearance to the cornea. In the clinical image graciously provided by Dr. Aldave, the cornea appears bluish white, and the slit beam shows that its thickness is two to three times normal. The cornea has a ground-glass appearance.
Histopathology: Congenital Hereditary Endothelial Dystrophy (CHED) is characterized by a markedly thickened stroma and Descemet's membrane (especially the posterior non-banded portion) with endothelial attenuation and vacuolization in a child. The two forms appear similar histologically. In the PAS stained image above, hydropic changes are seen in the epithelium (arrow 1), Bowman's layer is destroyed centrally (arrow 2) and there is stromal scarring (number 3), presumably secondary to the chronic nature of the corneal edema (loss of artifactual spaces in the stroma (number 3)). Descemet’s membrane does not contain guttae (arrow 4). The endothelium is markedly vacuolated (arrow 5). Interfibrillar granular material has been reported.
Treatment: includes 5% sodium chloride drops, in attempt to reduce the corneal swelling, or corneal transplantation, may be considered.

References: Vithana EN et al, Nature Genetics 2006 38, 755 - 757.

Table of Contents for Eye Pathology

CONJUNCTIVA

Choristoma

Hemangioma (Hamartoma)

Allergic Conjunctivitis (including Vernal, Atopic and Hayfever types)

Ligneous conjunctivitis

Amyloidosis

Superior Limbic Keratoconjunctivitis

Sarcoidosis (sarcoid granuloma) of the conjunctiva

Pinguecula

Spheroidal Degeneration

Nevus, conjunctiva

Melanosis of conjunctiva (benign, "complexion related")

Primary Acquired Melanosis of Conjunctiva

Conjunctival melanoma

Conjunctival dysplasia, squamous

Carcinoma-in-situ, conjunctiva, squamous

Squamous carcinoma, conjunctiva

Malignant lymphoma, conjunctiva

Oncocytoma

CORNEA

Salzmann's Nodular Degeneration

Band Keratopathy

Sclerocornea

Peter's Anomaly

Congenital Hereditary Endothelial Dystrophy

Blood Staining of the Cornea

Epithelial Downgrowth

Forceps Injury Induced Bullous Keratopathy

Fuchs Endothelial Dystrophy

Bullous Keratopathy

TGFB1 (BIGH3) Corneal Stromal Dystrophy

Macular Corneal Stromal Dystrophy

Keratoconus

LASIK Complications; Keratectasia and Scar

Pterygium

Acanthamoebic keratitis

Herpes Simplex Virus Stromal Keratitis

Fungal Keratitis

Congenital Syphilitic Keratitis (Interstitial keratitis due to Syphilis)

ANTERIOR CHAMBER AND TRABECULAR MESHWORK

Traumatic Angle Recession

Axenfeld Anomaly and Syndrome

Exfoliation Syndrome

Pigment Dispersion Syndrome

LENS

Rubella Induced Cataract

Marfan's syndrome- Lens Displacement

Anterior Subcapsular Cataract

Glaukomflecken

Cortical Cataract

Nuclear Sclerosis

Posterior Subcapsular Cataract

Posterior Lenticonus(Lentiglobus)

Mittendorf's Dot

Phacoanaphylactic Uveitis (Lens-Induced Granulomatous Inflammation)

Phacolytic Glaucoma

EYELID

Chalazion

Seborrheic keratosis

Freckle

Nevus

Molluscum Contagiosum

Xanthelasma

Syringoma

Eccrine Hidrocystoma

Solar Lentigo

Actinic Keratosis (solar keratosis)

Basal Cell Carcinoma

Sebaceous Carcinoma

Squamous Carcinoma

Melkersson-Rosenthal Syndrome

ORBIT

Dermoid Cyst

Cavernous Hemangioma

Pleomorphic Lipoma

Pleomorphic Adenoma of the Lacrimal Gland (Benign Mixed Tumor)

Adenoid Cystic Carcinoma of the Lacrimal Gland

Rhabdomyosarcoma

Solitary Fibrous Tumor

Malt Lymphoma

Phakomatous Choristoma

RETINA STUDY GUIDE

OPTIC NERVE

Cavernous atrophy of Schnabel

ACANTHAMOEBA

Acanthamoeba Keratitis
Definition: Acanthamoeba protozoa most commonly cause infection in soft contact lens wearers who do not take appropriate precautions in cleaning and sterilizing their lenses.
Incidence/ Prevalence: A dramatic rise in incidence occurred in the 1980s with contact lens wear. Estimates of incidence are about 1.4 cases/million population each year.(Ref 1)
Etiology: Acanthamoeba is a free-living genus of amoeba that is essentially ubiquitous in the freshwater, seawater, and air. The most frequently involved species are A castellani and A polyphagia.
Clinical Findings: Patients presenting with Acanthamoeba keratitis usually have severe eye pain, and a ring infiltrate. The infiltrate may have a dendritiform pattern that is confused with herpetic lesions. Special culture techniques and media, including nonnutrient blood agar layered with E coli, are required to grow Acanthamoeba. For a link to a clinical photograph click here.
Gross findings: Under the dissecting microscope the cornea will reveal a dense stromal infiltrate and occasionally the density of organisms is great enough for one to see numerous cysts. In the image shown cystic structures are provocative (arrow number 1) that correlated with the microscopic findings. In addition one can see ulceration of the surface and a very dense stromal infiltrate (arrow 2) that blurs the lamellar organization of the cornea. One appreciates the magnification of the dissecting microsope as one recognizes Descemet's membrane (arrow 3).
Histopathology: In most cases sections show a background of necrotizing keratitis with an interlamellar necrotic infiltrate. However, there may be little inflammation. As shown in the image with the bright arrow the organisms have a double walled cyst in microscopic sections that is characteristic. The organisms are quite visible with hematoxylin and eosin stained sections and are accentuated by PAS (see figure). Note the necrotic lamellae, keratocyte and lymphocyte nuclei in the corneal stroma. Other techniques, such as the use of monoclonal antibodies, may provide confirmation of the species for cysts and trophozoites in tissue sections. Electron microscopy beautifully demonstrates the morphologic features of the microbe but is unnecessary for diagnosis.
Air dried Geimsa stained smears or scraping of the cornea epithelium dramatically feature the organism with a cystic outerwall, a central contractile vacuole and single small nucleus and prominent nucleolus. Click to enlarge the photographic image below.
This is a MGG stained cytology smear of a scraping from the corneal epithelium, the organism(arrow) is slightly larger than the epithelial cells and show a distinct cell wall but a much smaller nucleus. The cytoplasm is markedly vacuolated, and there is the very distinctive central contractile vacuole used to pump water in and out of the cell. These features are very distinct from the other cells. Photograph original magnification x 400.
Treatment: A variety of topically applied therapeutic agents alone or in combination have been effectively used, including propamidine isethionate, clotrimazole, polyhexamethylene biguanide, and chlorhexidine. Penetrating keratoplasty is best reserved to restore vision after the acute infection has been effectively treated.

Reference:

1. Radford et al BJO 1998 82:1382.

2. Illingworth CD, Cook SD: Acanthamoeba keratitis. Surv Ophthalmol. 1998 May-Jun;42(6):493-508. Review

BIGH3 dystrophy- Lattice Phenotype

Definition- BIGH3 dystrophy is a group of phenotypically distinct corneal dystrophies as distinguished and named by clinical and morphologic characteristics. A single protein appears to be mutated in these dystrophies-keratoepithelin.

Etiology- All of these subtypes arise from mutations in the transforming growth factor beta-induced gene (keratoepithelin) on chromosome 5q31. Over 30 mutations have been described and more are being described all the time. There are 2 hotspots for mutations at Arginine 124 and Arginine 555 of the 683 amino acid 68 kDa protein, known as keratoepithelin. It is not understood how the specific mutations lead to different phenotypes, particularly since the same amino acid can be involved in a point mutation that results in completely different clinical and histologic characteristics. Numerous mutations especially in exons 4, 11-14 have been identified in variants of lattice corneal dystrophy (TGFBI).

Clinical Findings-

Histologic Findings-

Click on the photo to see enlarged view!
Congo red stain shows red-green dichroism with polarized light. The basis of the dichroism is a combination of of optical effects, the strongest of which are dispersion of
birefringence and linear dichroism superimposed on the smaller effects of circular dichroism
and optical rotatory dispersion. There are also fluorescent properties of congo red dye bound to amyloid and the birefringent nature of the protein that rotates the light. Normally white light is transmitted from the microscope thru the slide. A polarizer is placed over the light source that permits only one orientation of light to pass; the light is polarized. Upon illumination with polarized light fluorophores with the absorption transition dipole parallel to the electric vector of the excitation are selectively excited. Congo red is also a fluorophore and absorbs in the green spectral region of wavelengths with a peak absorbance at about ~480-500 nm. The emission (peak 540 nm) is partially polarized as well and there is a Stokes shift. The result is that the fluorescent emission is green (540nm) and polarized. Therefore green will be seen in fluorescence microscopy because it is the fluorescent light but the intensity will be low. However under the light microscope the effect of multiple color in the rotation of the second polarizer called an analyser is due to linear polarized light interacting with dye molecules and the rotation of light (Cotton effect). But red-yellow light will also be seen in some orientation because the amyloid protein has rotated light (the Cotton effect) from the intrinsic birefringence properties and it now has a different orientation. Counterclockwise rotation of the analyzer completely extinguishes the small retardation of the lower wavelengths and long red wavelengths but allows the passage of the wavelengths at the peak retardation. Yellow orange light thus passes the analyzer.
The congo red dye bound to amyloid protein will be seen as either green or yellow or red depending on the orientation of the fibril or the polarizer. Birefringence is characteristic of amyloid, dust, collagen and any crystalline material and so there may be other particles that appear bright. The dystrophies that feature this phenotype are called lattice dystrophy or Avellino dystrophy (the distinction between the two is in fact controversial) but the protein, keratoepithelin, has an expressed point mutation that may be identical to granular dystrophy and Thiel Behnke dystrophy (often misnamed as Reis Buckler's dystrophy) . A litany of mutations have been published but the usual is Arg124His.

To the left is a photomicrograph of the granular phenotype of BIGH3 dystrophy. Trichrome stain shows the bright red deposit at the arrow that obliterates part of the corneal epithelium and Bowman's layer to lie in the anterior stroma. The proteinaceous deposit is presumably a form of the encoded keratoepithelin protein, but the precise details as to the size, folding and association that permits multiple phenotypes has not been worked out yet.

MALT Lymphoma

Definition: MALT refers to mucosal associated lymphoid tissues. The MALT lymphoma is a proliferation of monocytoid B cells. The concept is that this type of lymphoid proliferation arises from lymphoid tissue that is normally found in mucosa such as the conjunctiva and GI tract.
Etiology: Recent studies suggest Chlamydia psittaci is responsible for conjunctival MALT lymphoma, and showed regression of ocular adnexal lymphoma after antibiotic therapy. The organism is found in about 80% of cases by PCR (Reference 1).
Incidence/Prevalence: By far this is the most common lymphomas of the conjunctiva and orbit. Previously considered as atypical lymphoid proliferations that could progress, the designation as MALT lymphoma permits the merging of MALT with the mainstream lymphoma classifications. There is a clear female predominance and older population for MALT.
Clinical Findings: These tumors may arise in the conjunctiva, eyelid, lacrimal gland and orbit. Generally, occurring in older individuals, more common in women, MALT lymphoma manifests in the orbit as a mass that molds around the eye or the so-called fish flesh or salmon patch under the conjunctiva. MALT lymphomas are generally insidious, indolent, progress slowly, and are characterized by recurrence many years following the initial diagnosis.
Histopathology: MALT Lymphoma is characterized by poorly defined follicular appearing areas that are composed of monocytoid B cells that feature enlarged nuclei. Click on the image below to enlarge.

At the periphery, lymphocytes appear smaller and sport round regular nuclei. Often the cytoplasm has a water clear appearance. The infiltrates are heterogenous with T cells, small lymphocytes, plasma cells and a variety of reactive lymphoid cells. Critical to the correct diagnosis is the establishment of a proliferation of atypical monocytoid B cells that expand and infiltrate the normal tissue. Immunohistochemistry marks the proliferating cells as B cells, CD20 positive and negative for CD 10 and CD 5. The cells may be CD 43 (sialophorin) positive and may show light chain restriction. Gene rearrangement studies will often show clonal gene rearrangement of B cell gene.
Treatment: Low dose radiotherapy in multiple courses with proper shielding has been the traditional treatment but recently some groups have reported success with chlorambucil. Other groups have noticed regression with doxycycline 100 mg bid x 3 weeks.
Prognosis: The prognosis is excellent with a 10 year survival of 73-86% and very few if any patients dying of MALT. However, many patients recur and there can be transformation to a more malignant lymphoma such as a large B cell lymphoma. Spontaneous regression of tumor may obfuscate treatment assessment.
References:

1. Ferreri et al. J Clin Oncology 2006; 23:5067

2. Ben Simon et al. Opthalmology 2006; 113:1209.

3. Suh et al. Int J Radiat Oncol Biol Phys. 2006 65;228-33. Orbital marginal zone B-cell lymphoma of MALT: radiotherapy results and clinical behavior.

Anatomy of the Human Eye-Cornea-Lens-Retina

The anatomy of the human eye is critical for a full understanding of the pathology. Please review one of our many links on this subject before tackling the pathology image library (click on link).

Cornea-Iris-Lens-Eye Anatomy

Photograph of a human eye that has been bisected in the coronal plane to show the view of the anterior segment from a posterior perspective (as though you are looking from the retina). The crystalline lens is suspended by delicate fibers called the zonule. The ciliary body (CB) is composed of about 72 processes that make up the pars plicata and a flat area called the pars plana. The ora serrata (ora) is the place where the retina joins the ciliary body. After reviewing the microscopic sections of an eye with a focus on the anatomy of the cornea your will be ready for images on corneal pathology.