by Roche Laboratories, Inc. should be instituted. Amgen Inc. also has an approved drug derived from interferon alpha called Infergen. The drug is injected subcutaneously three times a week. The authors have noted marked responses of Mooren’s- like ulcers to interferon alpha in patients with confirmed HCV infection. Many of these patients had been unresponsive to other forms of treatment. A newer treatment option is Rebetron, a Schering product that combines interferon with the antiviral drug ribavirin. A liver specialist should be consulted and participate in treatment, but the ophthalmologist should be prepared to impress on other specialists the severity of the Mooren’s ulcers if there is resistance to treatment because liver or other manifestations of the disease are minimal.

If chronic HCV infection is ruled out, then systemic immunosuppressive treatment can be considered, if local treatment measures are ineffective. Obviously, systemic immunosupression would likely be contraindicated in a patient with chronic HCV infection, so it is important to exclude this first. Systemic steroids should be administered first because immunosupression with chemotherapeutic agents does not take effect for several weeks. All systemic treatments should be performed in consultation with specialists knowledgeable in immunosupression.

●Initial treatment methylprednisolone 1 g/day IV in four divided doses; switch to 1 mg/kg/day prednisone PO with one of the following chemotherapeutic agents:

●Cyclosporin A 3 to 5 mg/kg/day;

●mMethotrexate 7.5 to 10 mg PO once a week administered with 1 mg/day folic acid;

●Azathioprine 2 mg/kg/day;

●Cyclophosphamide 2 mg/kg/day.

After several weeks of treatment the oral prednisone can be tapered. Frequent monitoring is needed to monitor the local response and systemic side effects of systemic immunosupression.

Local

●Cycloplegic agents (e.g. 0.5% scopolamine t.i.d.).

●Topical steroids (e.g. 1% prednisolone acetate or 1% prednisolone phosphate every hour).

●Topical cyclosporin A 0.05% twice a day.

●Prophylactic broad-spectrum topical antibiotics (e.g. 0.3% gatifloxacin q.i.d.).

●Bandage contact lens.

●Cyanoacrylate glue over small perforations may allow healing.

●Treatment of any concomitant eye disease (e.g. meibomianitis, blepharitis, dry eyes).

REHABILITATION

A large tectonic graft and then a central therapeutic graft may be attempted if all other systemic and local treatment measures fail. Lamellar tectonic grafts may add structural integrity to the thinned cornea. Conjunctival flaps may be necessary for severely thinned corneas. The use of contact lenses can correct irregular astigmatism in quiescent cases.

COMMENTS

Any later surgical interventions should be performed with concurrent immunosuppression, even in apparently burnt-out diseases because of a risk of recurrence. Corneal transplantation success is typically limited by vascularization of the cornea leading to a high-risk of transplant rejection.

REFERENCES

Brown SI, Mondino BJ: Penetrating keratoplasty in Mooren’s ulcer. Am J Ophthalmol 89:255–258, 1980.

Foster CS: Systemic immunosuppressive therapy of progressive bilateral Mooren’s ulcer. Ophthalmology 92:1436–1439, 1985.

Moazami G, Auran JD, Florakis GJ, et al: Interferon treatment of Mooren’s ulcers associated with hepatitis C. Am J Ophthalmol 119:365–366, 1995.

Wilson SE, Lee WM, Murakami C, et al: Mooren’s corneal ulcers and hepatitis C virus infection: A New Association. N Engl J Med 329:62, 1993.

Wilson SE, Lee WM, Murakami C, et al: Mooren’s-type hepatitis C virus (HCV)-associated corneal ulceration. Ophthalmology 1994;101:736– 745, 1994.

205 NEUROPARALYTIC KERATITIS

370.35

(Neurotrophic Keratitis, Trigeminal

Neuropathic Keratopathy)

Ian A. Mackie, MBChB, DO, FRCS, FRCOphth

London, England

Neuroparalytic keratitis is a disease that is the potential sequela to anesthesia administration in the region of the trigeminal nerve.

gresses despite local and systemic medical treatment. With the patient under topical or subconjunctival anesthesia, the conjunctiva is excised extending 2 clock-hours to either side of the ulcer and 3 to 4 mm posteriorly, leaving bare sclera. The use of topical antibiotics and steroids should be continued. Tissue adhesives and a therapeutic contact lens may be beneficial.

●Superficial lamellar keratectomy.

●A central island of anterior corneal stroma can be excised to arrest the inflammatory process and to promote reepithelialization. A lamellar corneal graft may be required.

acoustic neuromata, and herpes zoster ophthalmicus. In the course of treatment for the latter disease, about 8% of patients develop neuroparalytic keratitis. Other infrequent causes are trauma, tumors, multiple sclerosis, toxic chemical reactions, leprosy, and brain stem strokes and hemorrhages. Congenital forms, occurring notably in familial dysautonomia, (the Riley– Day syndrome) which occurs as a recessive disease in Ashkenazi Jews, may also be found. An idiopathic form has been described.

There is a notion that the disease is caused by dust and foreign matter lodging in an anesthetic eye, and protective

spectacles are often fitted. These contribute very little to the management of the disease.

COURSE/PROGNOSIS

A number of studies have shown that about 15% of patients with anesthetic eyes develop serious complications. These complications may develop soon or many years after the initiation of trigeminal insensitivity. The potential for neuroparalytic keratitis associated with trigeminal insensitivity can wax and wane. This is an important concept in the long-term management of these patients.

Discomfort or pain, of course, is not a feature at this stage. For this reason patients should be instructed to test their vision in the affected eye frequently. Such epithelial detachments can appear in an area of cornea covered by the top lid. A gap is seen in the epithelium that is surrounded by an area of undermined epithelium extending some distance beyond the gap, and folds rapidly appear in Descemet’s membrane. An aqueous flare and cells may be present.

Stage III develops when stromal lysis occurs. This may or may not be associated with infection, an early indication of which is a halo of cells in the stroma surrounding the stromal gap.

DIAGNOSIS

To develop a true neuroparalytic keratitis, one probably must have an insensitive eye in an insensitive environment. In other words, one must have an insensitive conjunctiva as well as an insensitive cornea for the typical pathologic process to present.

Sensation in either the cornea or the conjunctiva, which may occur after trigeminal nerve or gasserian ganglion destruction and which is often present after herpes zoster infection, spares the patient from the disease.

Conjunctival sensation should be tested by gently applying the tip of a hypodermic needle to the palpebral conjunctiva above and below. This test, together with the assessment of corneal sensitivity with a wisp of cotton wool or the corner of a folded paper tissue, has important practical considerations in diagnosis and prognosis. It is, for example, sometimes difficult to differentiate the viral epitheliopathy of herpes zoster from that of neuroparalytic keratitis. In this case, the demonstration of sensation in either the cornea or the conjunctiva implies a viral etiology. Furthermore, the prognosis for the cornea after an attack of herpes zoster or after a neurosurgical procedure can be established.

All patients with anesthesia of the eye and its environment produce excess mucus. The discharge often clings to the lashes. It is important to recognize this mucus as a feature of the anesthetic condition of the eye. It does not imply infection and it does not seem to be related to the presence or absence of keratopathy. The mucus comes from conjunctival subsurface vesicles, which are greatly increased in number in this condition.

The entire palpebral conjunctiva may stain with rose bengal after gasserian ganglion destruction. This staining is probably an index of increased conjunctival cell death. It does not mean that the eye is dry and it does not seem to be related to the development of keratopathy.

About 50% of patients with trigeminal anesthesia have abnormalities of the tear film and cornea. With fluorescein, geographic drying areas are often seen in the cornea, and transient blurring of vision is common at this level of the disease. Punctate erosive corneal epitheliopathy is also common. It may have a geographic distribution and may be extensive enough to lead to a drop in visual acuity. These signs so far described can be considered stage I of the disease.

Stage II develops as an acute episode and is characterized by epithelial detachment. The patient is usually first aware of a drop in visual acuity, and the eye may be somewhat hyperemic.

TREATMENT

Stage I

When severe, the punctate epitheliopathy is best treated with intermittent patching of the eye with tape, such as Blenderm (3M Health Care Ltd., Loughborough, LE11 1AP, England.) For a start, the eye may be patched for the whole of the wakeful day, but not during the night for fear of the tape coming in contact with the cornea. When the corneal epitheliopathy has been seen to disappear, the patching can be discontinued for one third of the wakeful day. The patient can pick the time for this uncovering to fit his or her social schedule. When again the cornea is seen to be clear, the patching can be discontinued for two-thirds of the wakeful day. As has been said before, the potential for having keratopathy waxes and wanes, and many patients will be able to proceed to uncovering the eye for the whole of the wakeful day. The tape used should be 2.5 cm wide and 6.25 cm long. The eye is shut by closing it with the top lid only, avoiding the tendency to squeeze the eye shut. The tape is held along the forefinger with about 1 cm in length being in front and unsupported by the finger. It is applied horizontally at first, to gain anchorage on the side of the nose, and then across the closed lids so that one third of the width of the tape adheres to the upper lid and two-thirds to the lower lid. Cutting the upper lid lashes greatly facilitates the application and retention of the tape. Smearing the scissors blades with petroleum jelly ensures that the cut lashes adhere to the blades and do not fall into the eye. Patients should be told to carry a mirror for periodic inspection of the closure. In the opinion of the author, mucomimetic drops do not have any influence on the punctate keratopathy of the insensitive cornea, but they seem to have some action in preventing the onset of the acute stage II of the disease.

The administration of oral tetracycline 250 mg twice daily or, better for compliance, doxycycline 100 mg on alternate days seems to diminish the amount of mucus produced by these insensitive eyes and may be continued for long periods.

Contact lenses have been advocated to control the keratopathy at this stage. However, they have several disadvantages; patients often lose their lenses during sleep, the keratopathy is difficult to assess under a contact lens, and fluorescein cannot be used without removing the lens and subsequently flushing the eye out with saline, for fear of staining the lens. The overwhelming disadvantage is the relatively frequent incidence of suppurative keratopathy. The patient is given no warning by way of pain, and the abscess is frequently well developed before a doctor is consulted. Even then, the wrong antibiotics may be prescribed by a doctor who is not familiar with the treatment of suppurative keratopathy in anesthetic, contact lens-wearing

In severe cases, multiple phlyctenules may be seen in the cornea and may affect the visual axis, leading to scarring and a decrease in vision. Stromal involvement is typically superficial; deeper involvement may occur in staphylococcal phlyctenulosis and may rarely lead to corneal perforation.

Most nodules of phlyctenulosis start in the limbus with dilated conjunctival vessels. The infiltration may travel toward the center of the cornea, with progressive necrosis and grayish infiltrates with superficial ulceration. Scarring of the phlyctenules may take the form of a spade at the limbus with a triangular scar. In severe cases, multiple phlyctenules are seen in the cornea, and Salzmann’s nodular degeneration may occur subsequently.

bral conjunctiva, and conjunctival scrapings show the presence of eosinophils. Patients have marked itching and may develop superficial punctate keratitis.

TREATMENT

Systemic

In staphylococcal blepharitis, patients older than 7 years can receive 100 mg doxycycline qd for 1 month.

Patients with tuberculosis should be given the appropriate systemic therapy for tuberculosis.

Laboratory findings

In patients with staphylococcal blepharitis, culture of the lids reveals Staphylococcus spp. In patients with tuberculosis, the tuberculin skin test is positive.

Conjunctival and corneal scrapings of phlyctenules initially may show evidence of mononuclear cells; in the late course of the disease, patients have polymorphonuclear cells. The epithelium shows degenerative epithelial cells. Usually, no eosinophils are seen in the scrapings.

Biopsy specimens of limbal phlyctenules show mononuclear cellular infiltration and polymorphonuclear cells in the epithelium and stroma. The mononuclear cells are predominantly T lymphocytes, monocytes/macrophages and dendritic cells. The T lymphocytes are mostly T helper/inducer cells. B lymphocytes and plasma cells are uncommon. The basal cell layers express HLA-DR antigens. The findings in phlyctenules are comparable to those observed in the human skin tuberculin reaction, which are considered to be classic examples of the delayed-type hypersensitivity response in humans.

Differential diagnosis

●Pingueculitis (inflamed pinguecula).

●Sterile peripheral corneal infiltrates.

●Marginal ulcers.

●Acne rosacea.

●Trachomatous pustule.

●Vernal keratoconjunctivitis.

●Infected peripheral ulcer.

The differential diagnosis of phlyctenulosis is important so as to initiate appropriate therapy. The corneal lesions of acne rosacea may closely resemble phlyctenulosis but have associated skin findings.

Pingueculitis shows no microinfiltrates. An increase in the amount of collagen in the substantia propria is seen after the pingueculitis subsides. There usually is a single lesion, there is no tendency to migrate into the cornea and there is no ulceration.

In cases of infected corneal ulcers, there is a demarcating margin with a tendency to infiltrate the center of the cornea.

In cases of peripheral corneal infiltrates, secondary to contact lenses, there is a history of contact lens use. The lesion shows no ulceration and does not migrate into the cornea.

In patients with vernal keratoconjunctivitis, the lesions are multiple with limbal hypertrophy and gelatinous infiltration of the limbus. The typical giant papillae are seen over the palpe-

Local

The lids should be carefully evaluated in cases of chronic staphylococcal blepharitis. Patients should receive a vigorous regimen of lid scrubs with an antibiotic/steroid ointment to be placed twice daily for a period of 2 to 4 weeks. This may be by cleaning of the lid margin with effective baby shampoo during showers. Baby shampoo may be used to scrub the lid margin, and eyelash scales should be removed with an effective antidandruff preparation. In young children, erythromycin ophthalmic ointment may be applied twice daily at the lid margin. In addition, 0.1% topical fluorometholone eyedrops or rimexolone (Vexol) eyedrops three times daily may be given for the corneal and conjunctival phlyctenules. The treatment of corneal and conjunctival phlyctenulosis may consist of 0.1% topical fluorometholone eyedrops or rimexolone eyedrops to be given every 6 hours for a period of 10 days. The topical treatment may be tapered to once daily over a period of 4 weeks. The intraocular pressure (IOP) should be monitored for steroidinduced glaucoma. A cycloplegic agent in the form of 1% tropicamide eyedrops may be given to patients with severe corneal involvement.

COMPLICATIONS

●Peripheral corneal scarring with vascularization.

●Central scarring in central corneal phlyctenules.

●Rarely corneal perforation.

●Loss of vision.

In patients with severe corneal scarring, penetrating keratoplasty may be required for visual rehabilitation.

REFERENCES

Abu El-Asrar AM, Van Den Oord JJ, Geboes K, et al: Phenotypic characterization of inflammatory cells in phlyctenular eye disease. Doc Ophthalmol 70:352–362, 1988.

Culbertson WW, Huang AJW, Mandelbaum SH, et al: Effective treatment of phlyctenular keratoconjunctivitis with oral tetracycline. Ophthalmology 100:1358–1366, 1993.

Helm CJ, Holland GN: Ocular tuberculosis. Surv Ophthalmol 38(3):229– 256, 1993.

Mondino BJ, Kowalski RP: Phlyctenulae and catarrhal infiltrates. Occurrences in rabbits immunized with staphylococcol cell walls. Arch Ophthalmol 100:1968–1971, 1982.

Ostler HB: Corneal perforation in nontuberculous (staphylococcal) phlyctenular keratoconjunctivitis. Am J Ophthalmol 79:446–448, 1975.

208 POSTERIOR POLYMORPHOUS

DYSTROPHY 371.58

Nicole J. Anderson, MD

Flowood, Mississippi

R. Doyle Stulting, MD, PhD

Atlanta, Georgia

●Histologic study of Descemet’s membrane shows a normal anterior banded zone in cases presenting after birth. The posterior non-banded zone is diminished or absent and is replaced by an abnormal posterior collagenous layer.

●Specular microscopy in vesicular PPD shows circular dark rings with scalloped edges around a light center. Band lesions appear as broad, mottled strips delineated by narrow, dark scalloped borders.

ETIOLOGY/INCIDENCE

Posterior polymorphous dystrophy (PPD) is a rare bilateral corneal disorder of Descemet’s membrane and the corneal endothelium. It is typically non-progressive and often noted as an incidental finding on ophthalmic examination. It can rarely cause reduced vision from corneal edema and glaucoma.

●Inheritance is autosomal dominant with variable expression. Some cases of autosomal recessive inheritance have been reported.

●The gene locus has been identified on the long arm of chromosome 20 (20q11) and is the same locus as that involved in autosomal dominant congenital hereditary endothelial dystrophy (CHED).

●Associations have been reported with Alport’s syndrome and keratoconus.

●The pathogenesis is believed to be a local metaplasia of endothelial cells to abnormal epithelial-like cells.

Differential diagnosis

●Iridocorneal endothelial (ICE) syndrome usually is unilateral and acquired. Endothelial cells are large and pleomorphic in ICE, rather than epithelial-like. There can be an overlap between ICE and posterior polymorphous dystrophy, causing speculation as to whether they represent different clinical entities or a spectrum of the same disease.

●Posterior corneal vesicle syndrome shows vesicles and band lesions similar to those of posterior polymorphous dystrophy, but it is unilateral and nonfamilial.

●Haab’s striae resemble band lesions but have scrolled, thickened edges with smooth areas within and do not have associated vesicles.

●In children born with cloudy corneas caused by posterior polymorphous dystrophy, the differential diagnosis includes congenital hereditary endothelial dystrophy, congenital hereditary stromal dystrophy, congenital glaucoma, birth trauma, congenital infection, metabolic disorders and sclerocornea.

COURSE/PROGNOSIS

●Typical corneal findings are present from an early age, but diagnosis is not usually made until the second or third decade.

●Most cases are asymptomatic and non-progressive.

●Corneal edema may develop in mid-life, or rarely at birth.

●Glaucoma, either open-angle or closed-angle, may occur. Glaucoma can result from overgrowth and contraction of the abnormal endothelium and basement membrane over the anterior chamber angle.

TREATMENT

In most cases, no treatment is necessary, as the disorder is usually non-progressive.

Ocular

●In mild corneal decompensation, topical sodium chloride drops or ointment can be administered.

●Elevated intraocular pressure should be treated medically or surgically.

DIAGNOSIS

Clinical signs and symptoms

●Slit-lamp examination shows one of three forms of the disorder. In the vesicular variant, small, round, vesicular lesions surrounded by a ring opacity are seen at the level of Descemet’s membrane. Band PPD is characterized by elongated bands of roughened Descemet’s membrane, with narrow, opaque, irregular ridges. In diffuse PPD, a large portion of the posterior corneal surface is invaded with a swirled pattern of thickened and opacified Descemet’s membrane.

Surgical

●In patients with corneal edema, penetrating keratoplasty may be necessary. Eyes with peripheral anterior synechia, elevated intraocular pressure, or both have a poor visual prognosis after penetrating keratoplasty.

●Posterior polymorphous dystrophy may recur in the graft after penetrating keratoplasty.

REFERENCES

Anderson NJ, Badawi DY, Grossniklaus HE, et al: Posterior polymorphous membranous dystrophy with overlapping features of iridocorneal endothelial syndrome. Arch Ophthalmol 119:624–625, 2001.

COMMENTS

Reis–Bücklers(CDB-I) and Thiel–Behnke honeycomb dystrophy (CDB-II) are dystrophies of Bowman’s layer that appear similar clinically. In the past, our understanding of these two entities was significantly impaired and confused by a lack of histologic and electron microscopic descriptions in the literature. Over the past decade, in large part due to advances in molecular genetics and the work of researchers in Europe and the United States, these dystrophies of Bowman’s layer have been redefined as two distinct entities.

REFERENCES

Afshari NA, Mullally JE, Afshari MA, et al: Survey of patients with granular, lattice, avellino, and Reis-Bücklers corneal dystrophies for mutations in the bIGH3 and gelsolin genes. Arch Ophthalmol 119(1):16–22, 2001.

Dighiero P, Valleix S, D’Hermies F, et al: Clinical, histologic, and ultrastructural features of the corneal dystrophy caused by the R124L mutation of the bIGH3 gene. Ophthalmology 107(7):1353–1357, 2000.

Klintworth GK: Advance in the molecular genetics of corneal dystrophies. Am J Ophthalmol 128(6):747–754, 1999.

Krachmer JH, Mannis MJ, Holland EJ: Cornea. 2nd edn: Philadelphia, Elsevier Mosby, 2005.

Küchle M, Green WR, Völcker HE, Barraquer J: Re-evaluation of corneal dystrophies of Bowman’s layer and the anterior stroma (Reis-Bücklers’ and Thiel-Behnke types): a light and electron microscopic study of eight corneas and a review of the literature. Cornea 14:333–354, 1995.

Mashima Y, Nakamura Y, Noda K, et al: A novel mutation at codon 124 (R124L) in the bIGH3 gene is associated with a superficial variant of granular corneal dystrophy. Arch Ophthalmol 117(1):90–93, 1999.

more diffuse systemic abnormality. The gene for the dystrophy has been mapped to human chromosome 1p36.2-36.3.

COURSE/PROGNOSIS

The corneal dystrophy progresses with age. Patients in their twenties demonstrate only a central corneal opacity, which may involve the entire stroma, central subepithelial cholesterol crystals, or both. These patients have excellent visual acuity with normal corneal sensation.

By age thirty, affected patients develop arcus lipoides. They may begin to note slight visual acuity reduction. Visual acuity is often considerably better than one would estimate based on slit-lamp appearance. The examination may detect the loss of Snellen visual acuity only if measured under daylight conditions. Corneal sensation also begins to decrease. Usually by age forty, patients develop a midperipheral panstromal corneal haze that fills in the donut-shaped area between the central opacity and the peripheral arcus. There will usually be some further reduction in visual acuity and corneal sensation. Often, arcus lipoides is so dense that it can be noted without the use of slitlamp examination. By their fifties, patients may require corneal transplantation because of the increased glare and decreased vision in the daylight.

Despite the name, only 51% of affected patients have crystalline deposits. This subset of patients without corneal crystalline deposition has been identified as having Schnyder’s crystalline dystrophy sine crystals. However, patients have been reported to have crystalline deposition in only one eye. Schnyder’s crystalline dystrophy may be detected as early as the first decade, but the diagnosis of Schnyder’s crystalline dystrophy sine crystals is more challenging and has been reported to be delayed up to the fourth decade.

210 SCHNYDER’S CRYSTALLINE

CORNEAL DYSTROPHY 371.56

Kristin M. Hammersmith, MD

Philadelphia, Pennsylvania

Peter R. Laibson, MD

Philadelphia, Pennsylvania

DIAGNOSIS

Clinical signs and symptoms

The clinical signs of the dystrophy may include a central corneal haze, subepithelial cholesterol crystal deposition, midperipheral panstromal haze and arcus lipoides. Systemic findings may include genu valgum and hypercholesterolemia.

ETIOLOGY/INCIDENCE

Schnyder’s crystalline dystrophy is a rare autosomal dominant disorder in which there is an abnormal bilateral deposition of cholesterol and lipid in the cornea.

There are no reports on the incidence of this dystrophy in the general population; the world’s largest pedigree of patients with Schnyder’s crystalline dystrophy has a Swede– Finn heritage and has been traced to the southwest coast of Finland.

The pathogenesis of the corneal changes is unknown, but it is thought to result from a localized defect of lipid metabolism. Abnormal elevations of serum lipid levels have been found in both affected and unaffected members of Schnyder’s pedigrees, but some affected members may also have normal serum lipid and cholesterol measurements. Abnormal lipid storage has been reported in the skin fibroblasts of affected patients, implying a

Laboratory findings

●Although rare sporadic cases have been reported, the vast majority of patients demonstrate a clear autosomal dominant inheritance.

●The corneal findings are predictable on the basis of patient age.

●The diagnosis may be more difficult in patients who do not demonstrate cholesterol crystals.

●Affected and unaffected patients should have serum lipid analysis because hyperlipidemias are frequent and should be treated.

●The loss of corneal sensation may be profound in more advanced cases.

Confocal microscopy has demonstrated loss of corneal nerves, large extracellular deposits and accumulation of highly reflective extracellular matrix.

●Histopathologic examination of corneal transplant specimens demonstrates panstromal deposition of unesterified and esterified cholesterol and lipids.

●Abnormal lipid deposition has rarely been found in basal epithelium and endothelial cells.

●Compared with normal corneas, cholesterol and phospholipid contents in affected corneas are increased more than 10and 5-fold.

●Apolipoproteins accumulate in the affected corneas, indicating preferential deposition of high-density lipoprotein.

Differential diagnosis

●The differential diagnosis is made up of systemic abnormalities affecting lipid metabolism and resulting in central corneal clouding including lecithin-cholesterol acyltransferase deficiency, fish eye disease and Tangier disease. These diseases are differentiated because they are of autosomal recessive inheritance, they do not demonstrate anterior stromal crystalline deposits, and they have low levels of serum high-density lipoprotein.

211 SUPERIOR LIMBIC KERATOCONJUNCTIVITIS 370.32

(Theodore’s Superior Limbic

Keratoconjunctivitis; SLK)

Timothy Y. Chou, MD

Rockville Centre, New York

Henry D. Perry, MD, FACS

Rockville Centre, New York

Eric D. Donnenfeld, MD, FACS

Rockville Centre, New York

Superior limbic keratoconjunctivitis (SLK) was first described by Theodore and Thygeson in the early 1960s. The disease is characterized by hyperemia and thickening of the upper bulbar conjunctiva in a ‘corridor’-like distribution, a fine papillary inflammation of the superior palpebral conjunctiva, punctuate

TREATMENT

●There is no local or systemic medical treatment that halts the progression of the corneal lipid deposition in this dystrophy.

●An alteration in serum cholesterol level has not been found to alter progression of the ocular disease.

ETIOLOGY/INCIDENCE

The cause of SLK is unknown. A viral etiology was suggested early on, but no viral particles have ever been identified histologically. There is an associated increase in incidence of thyroid dysfunction, but no other evidence that this is an autoimmune process. An allergic process is unlikely, as itching is not a typical symptom, topical corticosteroids have little benefit, and conjunctival scrapings reveal no eosinophils. Darrell described

thelial crystals if they are causing decreased vision.

REFERENCES

Garner A, Tripathi RC: Hereditary crystalline stromal dystrophy of Schnyder. II. Histopathy and ultrastructure. Br J Ophthalmol 56:400–408, 1972.

Theendakara V, Tromp G, Kuivaniemi H, et al: Fine mapping of the Schnyder’s crystalline corneal dystrophy locus. Human Genetics 114:594– 600, 2004.

Weiss JS, Rodrigues MN, Kruth HS, et al: Panstromal Schnyder’s corneal dystrophy: Ultrastructural and histochemical studies. Ophthalmology 99:1072–1081, 1992.

Weiss JS: Schnyder’s crystalline dystrophy sine crystals: recommendation for a revision of nomenclature. Ophthalmology 103:465–473, 1996.

Weiss JS: Schnyder’s dystrophy of the cornea: a Swede-Finn connection. Cornea 11:93–101, 1992.

eyelid, due to thyroid disease or inflammation, against a lax superior bulbar conjunctiva. The latter might be either agerelated or congenital. The resulting chronic rubbing and abnormal movement of the conjunctiva would then result in characteristic findings of SLK.

The condition is usually bilateral, but it may be unilateral and is often asymmetrical. This disease is most commonly seen in patients between the ages of 20 and 67, with a mean age of 49 years. It occurs more frequently in women than men by a 3 : 1 ratio. There is no seasonal, geographic, or racial predilection. Thyroid dysfunction is found in one-quarter to onehalf of patients, most often hypothyroidism or else severe Graves ophthalmopathy. One case of SLK was reported in a patient with hyperparathyroidism due to a parathyroid adenoma, with resolution of the condition following resection of the tumor. Dry eye (keratoconjunctivitis sicca) is commonly encountered, in up to half of patients.

involve one eye or both. In most cases, periods of remission gradually lengthen until the condition eventually resolves spontaneously. Vision is not usually affected. A superior limbal pannus may develop, and scarring of the superior tarsal conjunctiva is occasionally observed, but in general there are no other serious ocular sequelae.

DIAGNOSIS

Clinical signs and symptoms

Patients with SLK usually complain of burning, irritation, tearing, foreign body sensation, pain, photophobia, mucus discharge, blepharospasm and ptosis. Subjective discomfort often seems greater than the actual clinical findings. When filaments are present, symptoms tend to be exacerbated even more (Figure 211.1).

An important initial step to properly diagnosing SLK is to have the patient look downward while the examiner elevates the upper eyelids. In this way, the characteristic superior bulbar injection is observed (Figure 211.2). It is centered at 12 o’clock,

and typically arcs around the limbus for about 10 mm in the shape of an inverted trapezoid. On biomicroscopy, eversion of the upper eyelid reveals a nearly pathognomonic velvety papillary reaction along the tarsal conjunctiva. The superior bulbar conjunctiva is thickened and lusterless. Its tissue may be redundant and hypermobile. Superior limbal tissue is likewise thickened. The superior and paralimbal corneal epithelium demonstrates a fine punctate keratopathy and pannus. Filaments occur at the superior limbus and cornea in about one-third of cases. The abnormal superior conjunctival, as well as limbal and corneal surfaces stain intensively with rose bengal, and to a lesser degree with fluorescein. Corneal sensation and tear secretion, as measured by Schirmer testing, may be decreased.

Laboratory findings

Diagnosis is made based on history and characteristic clinical findings. Examination of scrapings of the involved bulbar conjunctiva may be helpful. Theodore and Ferry verified Thygeson’s observation that Giemsa-stained scrapings demonstrate keratinized epithelial cells. Scrapings of the upper palpebral conjunctiva show polymorphonuclear leukocytes. Biopsy of the involved bulbar conjunctiva reveals epithelial keratinization, dyskeratosis, acanthosis, balloon degeneration of the nuclei, intracellular accumulation of glycogen and hyalinized cytoplasm. There is stromal edema, as well as infiltration with polymorphonuclear leukocytes, lymphocytes and plasma cells. Goblet cells are markedly decreased. Electron microscopic examination shows a variety of nonspecific (degenerative) abnormalities within the nuclei of epithelial cells.

Patients should be advised to consult with their internists about thyroid function testing.

FIGURE 211.1. SLK with associated filamentary keratitis.

FIGURE 211.2. Classical injection pattern of the superior bulbar conjunctiva.

Differential diagnosis

The differential diagnosis is composed of conditions affecting the upper bulbar conjunctiva and cornea, and the upper palpebral conjunctiva, including the following:

●Contact lens-induced keratoconjunctivitis (CLK);

●Herpes simplex virus keratoconjunctivitis;

●Trachoma;

●Staphylococcal limbal keratoconjunctivitis;

●Floppy eyelid syndrome;

●Giant papillary conjunctivitis;

●Phlyctenular keratoconjunctivitis;

●Rosacea keratoconjunctivitis;

●Limbal vernal keratoconjunctivitis;

●Dysplasia;

●Neoplasm (case reported of sebaceous cell carcinoma misdiagnosed as SLK);

●Keratoconjunctivitis sicca;

●Retained superior perilimbal sutures.

Contact lenses can cause a keratoconjunctivitis that is clinically similar to SLK. There may be hyperemia of the superior bulbar conjunctiva, as well as irregular staining of and subepithelial infiltrates in the superior cornea. This masquerade syndrome may be related at least in part to thimerosal sensitivity and toxicity, and is not associated with thyroid dysfunction. In contrast to SLK, discontinuation of the contact lens in CLK is usually curative.

TREATMENT

Supportive

No medical therapy is effective in preventing the progression of corneal thinning. In the early stages, supportive therapy consists of spectacle correction of astigmatic refractive errors. With the progression of astigmatism, rigid contact lenses or ‘piggyback’ soft/rigid lens systems may be necessary.

nique causes the collagen to thicken, increasing the cornea’s stiffness and resistance to distortion and perhaps enzymatic digestion. Although the technique was described for treatment of keratoconus, itmay be applicable to Terrien’s degeneration as well. This slowly progressive, generally noninflammatory disease can usually be managed conservatively, but patients must be followed periodically for progression of thinning, which can threaten the integrity of the globe.

Surgical

In advanced cases of Terrien’s marginal degeneration, contact lens fitting may no longer be possible. In addition, ectatic areas may become dangerously thin. At this stage, surgical repair may be indicated both to decrease visually handicapping astigmatism and to prevent the rupture of ectatic areas through tectonic reinforcement.

Various surgical techniques have been suggested. One approach involves the excision of ectatic tissue, followed by suturing of the freshened edges of normal-thickness stroma. In another technique, a large eccentric penetrating keratoplasty is placed, although the increased possibility of graft rejection in such large transplants increases the chance of graft failure. An annular peripheral penetrating keratoplasty technique has also been described.

Inlay lamellar crescent keratoplasty has been used to treat severe thinning or perforation. With this technique, donor lamellar tissue-stroma, Bowman’s layer, and, in some cases, epithelium-may be obtained by hand dissection from a whole eye.

An alternative method involves the use of a trephine that conforms to the size and curvature of the leading edge of corneal thinning. A central donor corneal button is punched using the same size of trephine; only the peripheral cornea is retained to fill the crescent-shaped defect in the host corneal bed. A lamellar graft is anchored to one edge of the keratectomy bed and alternately, cut freehand and sutured in a stepwise fashion to fill the defect.

COMPLICATIONS

In the majority of cases, conservative management is indicated. Because of the thinning and ectasia in more advanced cases, mild trauma can result in rupture of the cornea. Patients should therefore be instructed to avoid situations in which the eye might be traumatized. The use of protective eyewear may be warranted. Patients should be cautioned to seek attention for any abrupt change in visual status or for the development of pain in the eye. Because of the high risk of corneal perforation, surgeons should avoid excising a pseudopterygium in patients with Terrien’s degeneration. In addition, surgery for corneal ectasia should be restricted to patients in whom astigmatism is severe and disabling or if perforation occurs or is imminent.

COMMENTS

Although Terrien’s degeneration is a rare disorder, it typically presents either when the patient becomes visually symptomatic because of progressive astigmatism or after recurrent episodes of ocular irritation.

Recently a technique of collagen cross-linking with riboflavin and UVA light has been described in a rabbit model. This tech-

REFERENCES

Caldwell DR, Insler MS, Boutros G, et al: Primary surgical repair of severe marginal ectasia in Terrien’s degeneration. Am J Ophthalmol 97:332– 336, 1984.

Goldman KN, Kaufman HE: Atypical pterygium: a clinical feature of Terrien’s marginal degeneration. Arch Ophthalmol 96:1027–1029, 1978.

Kaufman HE, McDonald MB, Barron BA, Wilson SE: Color atlas of ophthalmic surgery: corneal and refractive surgery. Philadelphia, JB Lippincott, 1992:147–166.

Robin JB, Sclanzlin DJ, Verity SM, et al: Peripheral corneal disorder. Surv Ophthalmol 31:1–36, 1986.

Wollensak G, Spoerl E, Seiler T: Riboflavin/ultraviolet A-induced collagen cross-linking for the treatment of keratoconus. AmJ Ophthalmol. 135:620–627, 2003.

213 THYGESON’S SUPERFICIAL PUNCTATE KERATOPATHY 370.21

(Thygeson’s Superficial Punctate

Keratitis)

Parveen K. Nagra, MD

Philadelphia, Pennsylvania

Thygeson’s superficial punctate keratopathy (TSPK) is a distinct clinical entity characterized by episodes of bilateral, coarse, granular, punctate epithelial opacities occurring without any ocular inflammation. Symptoms include a variable degree of ocular pain or discomfort, foreign body sensation, photophobia, and blurred vision.

ETIOLOGY/INCIDENCE

The cause is unknown. Association with viral infections has been suggested, although no definitive causation has been found. The prolonged disease course with steroid treatment may represent an altered immune response to a slow virus infection. A dyskeratosis has been postulated because of the steroidal response and the lack of inflammation in the eye. TSPK has been associated with HLA-DR3.

This keratopathy is very uncommon, affecting all races worldwide. Patients of both genders and all ages, including children, are affected.

COURSE/PROGNOSIS

TSPK is a chronic disease characterized by exacerbations and remissions. The lesions are transient, and the rate of recurrences is variable, although they often occur at weekly to monthly intervals. The natural history may be of eventual reso-

lution within 4 years. However, in patients treated with steroids, the morbidity may last decades. There are no corneal abnormalities between attacks. While the vision may be minimally affected during episodes, the long-term visual prognosis is excellent.

●Patients should have regular evaluations to assess for improvement, evaluate for complications of treatment, and taper steroids.

●Cyclosporin A and therapeutic soft contact lens are effective therapies to be considered initially, when difficulty arises in tapering steroids, or steroid-related complications are noted.

lium between lesions.

●No inflammation in the conjunctiva or anterior chamber; mild corneal stromal inflammation underlying the lesions may be present.

●Normal corneal sensation.

●Bilateral or unilateral.

Laboratory findings

●Lesions have elevated clusters of tiny gray dots, usually staining with rose bengal and fluorescein. May have a stellate appearance.

●Mucous filaments are not seen.

●No lab tests indicated.

Differential diagnosis

●Herpes simplex keratitis.

●Adenoviral keratitis.

●Staphylococcal keratoconjunctivitis.

●Keratoconjunctivitis sicca.

●Rosacea keratitis.

tomy but not laser in situ keratomileusis.

COMPLICATIONS

The potential complications of steroid therapy and extendedwear contact lenses must always be borne in mind. The use of idoxuridine eyedrops in TSPK may result in subepithelial opacities.

COMMENTS

TSPK is not a common or communicable condition. Because it is frequently misdiagnosed and is a periodically remitting disorder, numerous ocular drugs have been used with unmerited successes and not unexpected failures. Fortunately, there is usually no residual scarring and patients have an excellent long-term visual prognosis.

TREATMENT

Medical

Lubricants and topical steroids are the mainstay of treatment. Other treatments include topical cyclosporin A and therapeutic soft contact lenses. Following initiation of topical steroids, the lesions and symptoms improve rapidly.

●Fluorometholone 0.1% four times a day with slow taper over months.

●Alternatives include loteprednol 0.2%, loteprednol 0.5%, rimexolone 1%, or in advanced cases, prednisone acetate 1%.

REFERENCES

Darrell RW: Thygeson’s superficial punctate keratitis: Natural history and association with HLA DR3. Trans Am Ophthalmol Soc 79:486–516, 1981.

Fite SW, Chodosh J: Photorefractive keratectomy for myopia in the setting of Thygeson’s superficial punctuate keratitis. Cornea 20:425–426, 2001.

Goldberg DB, Schanzlin DJ, Brown SI: Management of Thygeson’s superficial punctate keratitis. Am J Ophthalmol 89:22–24, 1980.

Thygeson P: Clinical and laboratory observations on superficial punctate keratitis. Am J Ophthalmol 61:1344–1349, 1966.

Nagra PK, Rapuano CJ, Cohen EJ, et al. Thygeson’s superficial punctate keratitis: ten years’ experience. Ophthalmology. 111:34–37, 2004.