What is xanthelasma?

Xanthelasma
Definition: xanthomatous inflammation of the eyelid.
Incidence/Prevalence: Xanthelasma is the most common form of xanthoma of the skin. Xanthelasma tends to manifest in middle-aged to elderly individuals, predominantly females, but can be seen over a wide age range and children have been reported with the lesions.
Etiology: Xanthelasma has been associated with hyperlipoproteinemic states. All types of hyperlipoproteinemia including secondary forms have been linked to xanthelasma but types II and III, are present in 30%-40% of patients with xanthelasma. Some have argued that xanthelasma was a harbinger of premature death of the subject in the DeVinci painting (Mona Lisa).
Clinical Findings: Lesions are usually bilateral but may be single. Soft yellow plaques are located in the nasal aspect of the upper and lower eyelids.
Histopathology: Sections show collections of histiocytes with microvesicular foamy cytoplasm (arrow 1) clustered around vessels and adnexal structures within the dermis without significant numbers of accompanying lymphocytes or other inflammatory cells.





















At higher magnification cells with bean shaped nuclei contain foamy cytoplasm that is quite distinct (light arrow). Examination of adjacent cells demonstrates similar foamy histiocytes with a paucity of other inflammatory cells.
Treatment: The lesions are benign and removal is generally for cosmetic purposes and rarely for diagnosis. The lesions are usually surgically excised. Recently reports indicate that treatment with statin agents result in the disappearance of xanthelasma lesions. Steroids have been injected in the lesion. Carbon dioxide laser and topical trichloroacetic acid in various concentrations have been used to ablate xanthelasma.
Prognosis: Recurrence is quite common, almost 50% after surgical excision.

Reference:
Shields CL et al. Disappearance of eyelid xanthelasma following oral simvastatin (Zocor). Br J Ophthalmol 2005; 89:639-40.

What is seborrheic keratosis?

Seborrheic keratosis
Definition: benign neoplasm of the epidermis in which keratinocytes in G1 arrest are accumulated. The epithelial proliferation of the skin characterized by a stuck on appearance clinically and acanthosis and papillomatosis pathologically.
Incidence/Prevalence: the most common eyelid lesion in our surgical material accounting for more than half of all biopsies.
Etiology: There is evidence that P16, a cyclin-dependent kinase inhibitor, has a role in the etiology of the seborrheic keratosis. P16 is expressed in all of the cells of seborrheic keratoses, whereas normal keratinocytes expressed p16 only in the granular cells. Other factors such as cyclins A, D and E, p21, p53, Rb gene product, and TP1, are not expressed in SK cells.
Clinical Findings: Seborrheic keratoses occur most commonly in middle age and older individuals. They are often, oval, dome-shaped or verrucous and have a “stuck-on” appearance and vary in color from pink to brown. The lesion may range greatly in size from millimeters to centimeters. Irritated seborrheic keratosis, has been called inverted follicular keratosis. Most lesions are recognized easily clinically but many are often misdiagnosed as keratoacanthoma, basal carcinoma, actinic keratosis and even malignant melanoma (when they are pigmented). Squamous carcinoma in situ has been reported as a combined lesion in seborrheic keratosis. Sudden onset of multiple seborrheic keratoses is known as the Leser-Trélat sign and is associated with adenocarcinoma of the colon. The keratoses in this case may be part of an evolving acanthosis nigricans.
Histopathology: Histopathologically, several architectural patterns are described. The criteria used in the diagnosis are hyperkeratosis (very slight in the figure), acanthosis (arrow 1), and some degree of papillomatosis (the undulating epithelial infoldings at arrow 2 in the figure). Acanthosis, thickening of the epithelium (arrow 1) may take the form of proliferation of epithelium in interwoven or reticular tracts of epithelium (arrow 3), as abundant pseudohorned cysts, as a nested clonal pattern, as a hyperkeratotic pattern, and as a verrucous proliferation. The subdivision of the type of seborrheic keratosis has value only in the recognition of the broad range of appearances. Illustrated here is the reticular or adenoid type with double rows of epithelium (yellow arrow 3 in first image). A characteristic finding in most types of seborrheic keratoses is the formation of pseudohorn cysts, which is the appearance of concentrically laminated collections of surface keratin within the acanthotic epithelium. The pseudohorn cyst is nothing more than a section of invaginated keratinizing epithelium. Increased pigmentation may be seen on the basal layer of the epidermis probably due to melanin uptake by keratinocytes. The dark brown color of an otherwise typical seborrheic keratosis, may then be confused clinically with malignant melanoma. Many pathologists do not distinguish between squamous papilloma and seborrheic keratosis because the seborrheic keratoses exhibit papillomatosis in some areas that is indistinguishable from squamous papilloma and vice versa. In the illustration below one sees what was clinically a squamous papilloma (notice the base of the lesion is arrow 5 and the distinctive polypoid shape). Clearly the lesion features papillomatosis (arrow 4) and interwoven epithelial expansion typical of seborrheic keratosis (arrow 6). In yet another example of a clinical "squamous papilloma", there is clear evidence of a polypoid lesion (arrow 5 shows the base of the lesion) and the typical interwoven epithelial pattern characteristic of a seborrheic keratosis. This lesion even features pseudohorn cysts (arrow 7) a classic feature of the seborrheic keratosis. There seems to be little merit in separating the squamous papilloma and seborrheic keratosis in pathologic classification until or unless a clear etiologic difference is determined.

Treatment: Simple excision is often performed for diagnosis, cosmetic reasons and if the patient is irritated by the neoplasms. All specimens should be sent from histopathology as misdiagnoses abound. The all too frequent practice of discarding the lesion to save money from the histopathological analysis is essentially indefensible when a recurrent lesion in the same area proves to be a malignant melanoma years later. If the patient has the sudden onset of multiple lesions, referral for colonoscopy is indicated.

Reference: Nakamura, S. British Journal Dermatology 2003:149:560.

What is cavernous hemangioma?

Cavernous Hemangioma of the Orbit
Definition: a benign neoplasm of the orbit characterized by congeries of large endothelial lined blood vessels separated by thick fibrous septa that contain smooth muscle.
Incidence/Prevalence: cavernous hemangioma accounts for about 5% orbital biopsies at UCLA.
Etiology: unknown but some believe that they were derived from lymphangiomas.
Clinical Findings: Cavernous hemangiomas present at a median age of about 42 years with a range between 18 and 70 in some series. There is a slight female predominance. The tumors grow slowly and are usually intraconal. With impingement on the optic nerve visual field defects such as an enlarged blind spot occur. Hyperopia may be induced by the compression of the eye. CT contrast injection fills quite slowly; separating this tumor from schwannoma, neurofibroma, hemangiopericytoma, etc.
Pathology: The gross appearance is characteristic with a nodular mass that has been likened to a cluster of grapes. On cross section the appearance is distinctive with large (~1mm diameter) cavernous spaces filled with blood and separated by fibrous septae (white in the image). Note the green ink on the capsule of this tumor. Microscopic examination shows endothelial lined channels that contain fibrous septae (blue on trichrome stain in the images). On higher magnification the septae are generally fibrous (2) but contain occasional smooth muscle cells in some areas of the wall. In the high power image the septa have been captured in an unusual tangential section that gives the appearance of a very wide septum. In this orientation smooth muscle cells are particularly obvious as they appear red in color (arrow 3) but are easily distinguished from erythrocytes in the cavernous spaces (number 1). In longstanding cases there is often thrombosis with organization, hemorrhage and chronic inflammation.
Treatment: Excision is advocated by most, although some authors indicate that following small tumors may be adequate. The risk with surveillance is delay in diagnosis if the clinical diagnosis is in error.
Prognosis: Surgery is generally curative but the induced hyperopia and choroidal folds may persist. Deep apical lesions may present difficult in removal without injuring the optic nerve, extraocular muscles, or orbital nerves.

What is epithelial downgrowth?

Epithelial Downgrowth
Definition: Epithelial downgrowth is the proliferation and extension of surface squamous epithelium through a wound to line the inner tissues and cavities of the eye.
Etiology: Squamous epithelium enters the eye through poorly apposed or poorly healed surgical wounds or a traumatic breech in the eyewall. Usually the epithelial cells enter through a gap in cornea.
Incidence/Prevalence: The incidence of epithelial downgrowth after penetrating keratoplasty in one series was 0.2%. Cataract surgery was the most common predisposing surgical procedure accounting for about 86% of cases in a 30 year study. Penetrating keratoplasty accounted for 12% of the cases. The incidence in cataract surgery has fallen precipitously with smaller wounds and better attention to wound closure. Epithelial downgrowth also occurs after evisceration.
Clinical Findings: The clinical findings may be subtle and are often unrecognized. Two basic types have been emphasized. The diffuse type is associated with sheets of epithelium that cover the trabecular meshwork and iris. If the trabecular meshwork is covered then elevated intraocular pressure is usually abrupt in onset and unresponsive to therapy. A smooth iris membrane may be visible. The diffuse type has a poor prognosis. The cystic type of epithelial downgrowth is more benign.
Histopathology: Stratified squamous epithelium that is quite similar to normal corneal epithelium can usually be identified on the posterior corneal surface. Sometimes, the wound responsible can be traced in sections. In the case shown above, severe dry eye disease resulted in a corneal ulcer. The ulcer eventually worsened and perforated. A conjunctival flap (arrow 2) was pulled over the defect, which now shows marked thinning (arrow 3) which resulted in a perforation. Epithelial downgrowth was not recognized clinically and the patient eventually had phthisis bulbi and was eviscerated. Epithelial downgrowth is evident lining the posterior surface of the cornea (arrow 3) and iris (arrow 4). Click on the photo to compare the epithelium of the cornea to that of the downgrowth (arrow 3) and that of the flap (arrow 2).

The relentless epithelium has grown on the surface of the iris and resulted in anterior synechiae. The downgrowth (arrow 2) is evident adjacent to both the iris and Descemet's membrane (arrow 5). Arrow 4 features typical iris blood sheathing of loose collagen permitting the clear identification as iris.

The stratified squamous epithelium (arrow lit) can be seen lining gliotic retina (arrows 6) that has previously detached (no photoreceptors are visible).

Stratified squamous epithelium (arrow 9) can also be seen on the surface of ciliary processes adjacent to the non pigmented ciliary epithelium of ciliary processes (8).
Treatment: Complete excision of the membrane is necessary. In the diffuse type many authors have called for radical block excision with cornea-scleroplasty. Some authors report success with simple excision.
Prognosis: The diffuse type often results in phthisis and enucleation. The recurrence rate is about 50% even after excision.
References:
1. Weiner MJ et al. Epithelial downgrowth. Br J Ophthalmol 1989;73:6-11.
2. Sugar et al Arch Ophthalmol 1977.
3. Ghaiy et al. 2005 Arch Ophthal 9: 1268

What is a forceps injury to the cornea?

Forceps Injury to Descemet's membrane
Definition: rupture of Descemet's membrane at birth due to trauma from application of delivery forceps.
Etiology: Descemet's membrane is quite thin at birth and susceptible to trauma. Forceps applied on the cornea may stretch or tear Descemet's membrane in multiple areas.
Incidence/Prevalence
Clinical Findings: The resulting linear breaks in Descemet's membrane from forceps trauma may produce visual symptoms such as astigmatism, glare, and even visual loss and amplyopia. Histopathology: Most cases of forceps injury are viewed at the time of PKP, many years after the initial injury. As in the image of a PAS stained cornea shows, the breaks may be multiple (arrows 1) and characterized by focal scrolling and intense thickening of Descemet's membrane. Presumably this is caused by the exuberant growth of Descemet's membrane in order to heal the breaks. In addition there is hydropic change within the epithelium (arrow 2) which is seen at low magnification as the wash out of pink color in the cytoplasm. Enlarge the figure and view the microbullae (arrow 3) that have developed from the resulting bullous keratopathy. Stromal scarring accompanies the process (number 4) seen of course as a paucity of nuclei in focal regions of the stroma. Sectioning artifact, in the microtome plane of scrolled Descemet's membrane is quite common in these cases (arrow 5). Endothelium is markedly attenuated (arrows 1 and 8 below). Higher magnification of the nodular thickening at the site of injury (arrow 6). The configuration of the nodule suggests that endothelial cells laid down layer after layer of basement membrane material (arrows 7) that were misoriented because of the gap, migrated to the edge and finally filled it at the other side. Endothelial cells are evident on the nodule (arrow 8) but are even more sparce elsewhere. Others have reported epithelial transformation of endothelium with this injury (1).

Treatment: The corneal edema resulting from the trauma can be treated symptomatically and if the initial injury was severe enough a penetrating keratoplasty may be needed eventually.
References:
1. Tetsumoto, K et al. Epithelial transformation of the corneal endothelium in forceps birth-injury-associated keratopathy.Cornea, 1993;12:65-71

What is sebaceous carcinoma?

Sebaceous Carcinoma of the Eyelid
Definition: Sebaceous carcinoma is a malignant neoplasm arising in sebaceous glands that is characterized by extensive lipid production.
Incidence/Prevalence: Sebaceous carcinoma is considered the second most common malignant neoplasm of the eyelid accounting for about 5% of all primary eyelid malignancies (basal cell carcinoma 90%, squamous carcinoma 4% and malignant melanoma 1%). About 70% occur in women and the mean age range from a variety of series is between 57-72 years.
Etiology: Sebaceous carcinoma of the eyelids may arise in the meibomian glands of the tarsus, the glands of Zeis in the skin of the eyelid, or the sebaceous glands of the caruncle.
Clinical Findings: The key clinical feature is thickening of the eyelid which is present in about 57% of cases. About 43% present with a nodule. Clinical diagnosis is often missed (about 68% of the time) or delayed because of this lesion’s propensity to mimic or accompany a chalazion, and/or produce chronic blepharoconjunctivitis. There are more Meibomian glands in the upper lid than the lower lid. This may account for the greater frequency of sebaceous carcinoma in the upper lid. When sebaceous carcinoma is suspected clinically, the pathologist should be alerted so a strategy can be put in place for documentation of lipid within tumor cells, e.g. glutaraldehyde and paraformaldehyde fixation with osmication or frozen sections for lipid stains. Survival rates for sebaceous carcinoma are perhaps slightly worse than those for squamous cell carcinoma but have improved in recent years as a result of increased awareness, earlier detection, more accurate diagnosis, and appropriate treatment. Metastases first involve regional lymph nodes and occur in about 30% of cases.
Histopathology: Sebaceous carcinoma is initially misdiagnosed by the general pathologist about 50% of the time; the diagnosis is usually given as squamous carcinoma. This is not an egregious error because both sebaceous and squamous carcinoma require complete excision. There is some evidence that the prognosis is similar for both entities. Sebaceous carcinoma infiltrates and destroys the architecture of the eyelid. In the macroimage of the cross section of an eyelid one can identify the epidermis (arrow 1), normal cilia (arrow 2) and superficial dermal hemorrhage (arrow 3). Complete effacement of Meibomian glands of the eyelid is due to infiltration by a white tumor (number 4) that appears to have its center where the Meibomian glands usually are located in the lid. Even in the gross, glands of Zeis are visualized; note the cilia emanating from the lid (arrow 5). A comparison is afforded by this histologic section that is taken correlatively within about 100 microns from the gross photo. The structures are numbered similarly for your comparison. In the higher magnification image, the malignant neoplasm features large cells with vesicular bubbly cytoplasm (arrow 6). The clear foamy cytoplasm represent empty spaces presumably occupied by lipid prior to organic solvent extraction during processing. The nuclei are enlarged and have prominent nucleoli. Mitotic figures abound (arrow 7). The demonstration of lipid within the cytoplasm of tumor cells by special stains is a prerequisite for the diagnosis. Our laboratory prefers to osmicate the tissues with osmium tetroxide, which is a classic method of fixing lipid. This can be done on formalin fixed material which provide the pathologist flexibility in dealing with a wide range of clinical colleagues. One micron plastic sections are stained with toluidine blue. The lipid appears bright green in section (arrows 8). Alternatively oil red O or Sudan black staining, can be performed on frozen section, but typically these may be quite difficult to interpret. Adequate frozen sections are notoriously difficult to obtain from skin. Immunohistochemistry may be helpful when documentation of lipid is not feasible (paraffin sections are all that is available). Positive reactivity to antibodies to CAM5.2 and EMA are often positive in sebaceous carcinoma and negative in squamous carcinoma and basal cell carcinoma, respectively. The illustration shows anti-CAM5.2 reacting strongly with infiltrative nests cells of a sebaceous carcinoma. Pagetoid spread of sebaceous carcinoma is quite typical with tumor cells replacing the epithelium. Clusters and single cells may infiltrate the epithelium at various levels. Another pattern in the conjunctiva is that of complete replacement of conjunctival epithelium by tumor cells. A rare variant of sebaceous carcinoma involves only the epidermis and conjunctiva without demonstrable invasive tumor. The distribution of sebaceous carcinoma often is irregular and may feature skip lesions. The prudent surgeon will often map the tumor with tiny multiple biopsies from numerous sites on both lids prior to or during the excision of the main tumor.
Treatment: In most cases complete removal of the malignant neoplasm is the treatment of choice. Exenteration is sometimes (about 13% in some series) performed for larger or deeply invasive tumors. Because sebaceous carcinoma tends to be multifocal, an approach using Moh's surgery may result in incomplete removal of the tumor.

Prognosis: The recurrence rate is about 18% in the hands of Shields et al. and 8% produce distant metastases. The mortality due to sebaceous carcinoma has been estimated by others to be about 3%.

References:

Muquit et al. Eye 2004 18:49-53.

Shields JA et al. Survey of Ophthalmology 2005; 50:103-122

What is squamous cell carcinoma?

Squamous cell carcinoma of the Eyelid
Definition: malignant neoplasm arising in and with differentiation toward stratified squamous epithelium
Incidence/Prevalence: Squamous cell carcinoma is at least 10 to 40 fold less common than basal cell carcinoma in the eyelids, which accounts for about 90% of eyelid primary maligancies. Squamous carcinoma is the third most common eyelid malignancy accounting for about 4% of all primary eyelid malignant neoplasms. Sebaceous carcinoma accounts for slightly more (5%).
Etiology: UV radiation is a clear factor in the cause of squamous cell carcinoma of the eyelid. The majority of squamous cell carcinomas arise in solar-damaged skin and premalignant lesions (actinic keratoses). Mutations of p53 are high in patients with actinic keratosis. One theory is that the formation of pyrimidine dimers from UV radiation in the p53 gene results in the inability to produce cell-cycle arrest in G1. The absence of cell cycle arrest impairs repair and/or elimination of damaged DNA and division continues of the mutant cells.
Clinical Findings: The clinical appearance is diverse, ranging from ulcers to plaques to fungating or nodular growths. The lower eyelid is more frequently involved than the upper.
Histopathology: The criteria for the diagnosis include atypical squamous cells forming nests and strands and infiltrating the dermis with squamous differentiation. In the accompanying image, surface ulceration is evident (number 1). Large nests of well differentiated squamous epithelium with central keratin (keratin pearls)are present (number 2). Strands and isolated nests of malignant cells infiltrate the dermis (arrows 3). At higher magnification (middle image) the central keratin in the pearl is more visible (arrow 4) and strands of infiltrating atypical squamous epithelium (arrow 5) extend into the dermis. At high magnification, (lower image) the central keratin in the dyskeratotic whorl of cells is obvious (arrow 6) and intercellular bridges (desmosomes or epithelial attachments) can be best visualized in edematous areas between cells as very thin lines attaching adjacent cells (arrow 7). Occasional mitotic figures are evident (arrow 8). In this series the extensive squamous differentiation in the form of keratin formation, pearls, and intercellular bridges indicate a well differentiated squamous carcinoma.
Treatment: Complete excision of the tumor is considered the best treatment and in small lesions may be curative.
Prognosis: Squamous carcinoma may invade perineurally and through lymphatics. Regional lymph node metastasis is reported to occur in 1%-21% of patients with squamous cell carcinoma of the eyelid.

What is basal cell carcinoma?

Definition: malignant neoplasm of the skin arising from the basal layer of the epidermis
Incidence/ Prevalence: Basal cell carcinoma accounts for about 90% of eyelid malignancies and about 80% of skin malignancies. Over 1 million cases of basal cell carcinoma occur in the U.S. each year and many of them are on the face, well within the domain of the ophthalmologist.
Etiology: As the name implies, basal cell carcinomas presumably originate from the stratum basale, or stratum germinativum, of the epidermis. UV exposure (especially episodic) is a key risk factor for the tumor. There is evidence of abnormalities in the sonic hedgehog signalling pathway. Sonic hedgehog protein (SHH) binds to a transmembrane tumor suppressor protein abbreviated PTCH1. This binding prevents the normal interaction with another transmembrane protein (SMO). SMO interacts through the GL1 family of transcription factors (Reference 1 below).
Clinical Findings: The classic description is a “rodent” ulcer—that is a slowly enlarging ulcer with pearly, raised, rolled edges. In the photograph of the eyelid basal cell carcinoma the borders are clearly raised (short arrows) and a multinodular contour is evident. There is loss of eyelid cilia focally (arrows 1 and 2) associated with a depression in the center of the lesion (white arrow 2). There are dilated vessels at the eyelid margin (white arrow 3). Morpheaform or fibrosing basal cell carcinoma presents as a flat or slightly depressed pale yellow indurated plaque. Lesions typically occur on the face, and the lower eyelids are more commonly involved than the upper eyelids. Tumors in the medial canthal area are more likely to be deeply invasive and to involve the orbit.
Histopathology: The characteristic features and criteria for the diagnosis of basal cell carcinoma include

the nodular architecture conferred by the tumor and nests of basaloid cells that extend in contiguity from the basal layer of the epidermis and have a similar appearance to the stratum basale (arrow 1 above).

The nests and strands exhibit peripheral palisading. Usually single cells ring the nests with their long axis oriented radially from the center of the nest creating a picket fence arrangement. Black arrow 2 above and below.

Tumor nests exhibit retraction artifact where there is a cleft created from processing between the nests and the surrounding stroma (Arrows 2 above, and 2 & 5 below).

Cytologic features include the crowding of tumor cells, which exhibit nuclear enlargement and hyperchromasia with a variable amount of atypia. In some tumors the cytologic changes may seem somewhat bland. Anaplastic features are uncommon. Basal cell carcinomas may exhibit a variety of cytologic and architectural patterns, including morpheaform, squamous, sebaceous, adenoid (arrow 4 above), and cystic differentiation. The morpheaform, or fibrosing, basal cell carcinoma, is often infiltrative, and its extent is difficult to determine clinically. Inflammation often accompanies basal cell carcinoma (number 3 above, no arrow).
Treatment: Complete excision is considered the treatment of choice. Notice in the first image above there is green ink at the edge of the specimen indicating that the margin is positive, (arrow number 3) If the lesion is characteristic clinically, many clinicians will attempt a complete excision on the first operation while others prefer a small biopsy followed by complete excision. Some will attempt to use frozen section and Moh’s procedures if the lesion involves the medial canthus. In our referral practice we have seen frozen sections of skin misinterpreted. For example the hair follicle apparatus is frequently misinterpreted as basal cell carcinoma. This is generally due to the difficulty presented in getting high quality sections from frozen skin. We advocate using a rapid turnaround with paraffin embedding for reconstruction if the initial excision is not complete. That being said, one should remember that only about 30-40% of basal cell carcinomas recur even when the margins of excision are positive.
Prognosis: Morbidity in basal cell carcinomas is almost always the result of local spread; metastatic spread is extremely unusual. The early lesion is curable and quite simple to extirpate but often missed by the less observant.

Reference: Rubin AI et al. NEJM2005; 353:2262-2269.

What is allergic conjunctivitis?

Definition: Allergic keratoconjunctivitis is a group of distinctive clinical disorders that are largely IgE mediated hypersensitivity reactions but have quite similar histopathology (so we group them here). These disorders include "Hay Fever Conjunctivitis," Vernal keratoconjunctivitis (VKC) , and Atopic Keratoconjunctivitis.
Incidence/ Prevalence: Hay Fever Conjunctivitis may occur in patients with asthma and allergic rhinitis. VKC occurs most commonly in boys with a history of atopy, asthma, allergic rhinitis and eczema. Named "vernal" because patients are affected in the spring, VKC can be year round in tropical climates. Atopic keratoconjuncitivitis occurs frequently in patients with atopic dermatitis. It has been written that VKC accounts for about 0.1-0.5% of visits to the eye clinic and allergic conjunctivitis affects about 20% of the world's population.
Etiology: probably a variety of allergens and pollens. However, VKC is not associated with a positive skin test or RAST in 42-47% of patients, suggesting it is not solely an IgE-mediated disease. On the basis of challenge studies as well as immunohistochemical and mediator studies, a Th2-driven mechanism with the involvement of mast cells, eosinophils, and lymphocytes has been suggested. Th2 lymphocytes are responsible for both hyperproduction of IgE (interleukin 4, IL-4) and for differentiation and activation of mast cells (IL-3) and eosinophils (IL-5). Some studies have suggested the involvement of neural factors such as substance P and NGF in the pathogenesis of VKC. The overexpression of estrogen and progesterone receptors in the conjunctiva of VKC patients raises a possible role for sex hormones. Perhaps the pathogenesis of VKC is multifactorial, with the interaction of the immune, nervous, and endocrine systems.
Clinical Findings: VKC is an allergic eye disease that especially affects young boys. The most common symptoms are itching, photophobia, burning, and tearing, irritation, mucoid discharge and eyelid swelling. Most common signs are giant papillae, superficial keratitis, and conjunctival hyperemia. The symptoms are similar in the other forms of allergic conjunctivitis but the time of onset, seasonal nature, chronicity and details of allergen exposure will vary according to the type.
Histopathology: As seen in the photograph the epithelium is thickened and spongiotic (intercellular edema or as seen here separation of epithelial cells). There is dramatic hyperemia in the substantia propria and a chronic inflammatory infiltrate with numerous eosinophils. However, most important is the exocytosis of eosinophils within the epithelium (green arrow). The surface shows a desquamation of epithelium and inflammatory cells. Limbal papillae may occur in vernal keratoconjunctivitis (Horner-Trantas dots).
Treatment: Many of the treatment regimens are similar in all these forms of allergic conjunctivitis. Removal of the offending allergen and treatment with topical vasoconstrictors, mast cell stabilizers such as cromolyn sodium, topical nonsteroidals, cyclosporin in severe cases, and topical steroids (best avoided if possible) have been used. If steroids are used topically or by lid injection, careful surveillance of intraocular pressure is indicated.

What is macular dystrophy of the cornea?

Macular Dystrophy of the Corneal Stroma
Definition: an inherited corneal stromal dystrophy characterized by deposition of acid mucopolysaccharides in the corneal stroma.
Incidence/Prevalence: Macular dystrophy is much less common than BIGH3 dystrophies
Etiology: Macular dystrophy exhibits an autosomal recessive pattern of inheritance. The gene involved in macular dystrophy is a carbohydrate sulfotransferase gene (CHST6) on chromosome 16q22. Two types of macular dystrophy have been described depending on the absence in the production of keratan sulfate (type I) and presence (albeit reduced) of keratan sulfate and dermatan sulfate-proteoglycan (Type II). In type I, homozygous mutations of the missense, deletion and frameshift type occur that result in the absence of production. In Type II, mutations are found upstream from CHST6 suggesting a regulatory pathway is involved. Both types of mutations may be seen in the same family and the result is deposition of “unsulfated keratan sulfate”.
Clinical Findings: Macular stromal dystrophy eventually involves the entire cornea to the limbus in a diffuse pattern of poorly defined stromal white gray areas with intervening hazy stroma. The entire stromal thickness may be affected. In the figure notice that the grey white deposits extend all the way to the limbus (arrow 1). Corneal erosions and stromal thinning may occur.
Histopathology: Acid mucopolysaccharide material is deposited both intracellularly and extracellularly in the corneal stroma. The deposits stain blue with the alcian blue and colloidal iron stains. The blue color in the figure is Alcian blue positive glycoaminoglycans acid mucopolysaccharides (unsulfated keratan sulfate).
Treatment: Penetrating keratoplasty is advocated as the main treatment although recurrences have been described.
References:
Akama TO et al. Macular corneal dystrophy type I and type II are caused by distinct mutations in a new sulphotransferase gene.Nat Genet. 2000 Oct;26(2):237-41.