Fine BS, Yanoff M, Pitts E, Slaughter FD: Meesmann’s epithelial dystrophy of the cornea. Am J Ophthalmol 83:633–642, 1977.

Irvine AD, Corden LD, Swensson O, et al: Mutations in cornea-specific keratin K3 or K12 genes cause Meesmann’s corneal dystrophy. Nat Genet 16:184–187, 1997.

Meesmann A: Über eine bisher nicht beschreibene dominant vererbte Dystrophia epithelialis corneae. Ber Dtsch Ophthalmol Ges 52:154, 1938.

Pameijer JK: Über eine fremdartige familiare oberflächliche Hornhautveränderung. Klin Monatsbl Augenheilkd 95:516, 1935.

Roca PD: Meesmann’s hereditary epithelial dystrophy (differential diagnosis). Eye Ear Nose Throat Mon 48:424–425, 1969.

Swensson O, Swensson B, Nolle B, et al: [Mutations in the keratin gene as a cause of Meesman-Wilke corneal dystrophy and autosomal dominant skin cornification disorders]. Klinische Monatsblatter für Augenheilkunde 217(1):43–51, 2000.

Thiel HJ, Behnke H: [On the extent of variation of hereditary epithelial corneal dystrophy (Meesmann-Wilke type)]. Ophthalmologica 155:81– 86, 1968.

Thiel HJ, Caesar R: [Histologic and electron microscopic studies of hereditary corneal epithelial dystrophy (Meesmann-Wilke)]. Albrecht Von Graefes Arch Klin Exp Ophthalmol 174:134–142, 1967.

Tremblay M, Dube I: Meesmann’s corneal dystrophy: ultrastructural features. Can J Ophthalmol 17:24–28, 1982.

200 KERATOCONJUNCTIVITIS SICCA AND SJÖGREN’S SYNDROME

370.33

James V. Aquavella, MD

Rochester, NY

ETIOLOGY/INCIDENCE

Sjögren syndrome is an autoimmune disease consisting of xerostomia (dry mouth), keratoconjunctivitis sicca, often associated with dryness of the nasal and genital mucosa. Primary Sjögren’s is seen in individuals with the systemic immune dysfunction in the absence of connective tissue disease as well as in individuals lacking both systemic dysfunction and connective tissue disease. Secondary Sjögren’s includes patients with defined connective tissue disease (rheumatoid arthritis, lupus).

The exact incidence is unknown; one Swedish study suggests 0.4% prevalence. Estimates for the United States are between 1 and 2%. There is a nine to one prevalence for females, and the condition is most often seen in postmenopausal women although there are a number of reports of women afflicted in their 20 s and 30 s.

One of the prime findings is lymphocyte infiltration of secretory glands. While the lachrymal and salivary glands are most frequently effected a more widespread involvement of secretory glands is not unusual.

DIAGNOSIS

Clinical signs and symptoms

Ocular signs and symptoms are similar to those of other dry eye conditions. Burning, itching, foreign body (sandy) sensation, mucous discharge, photophobia and blurred vision may be present. The condition usually is more comfortable in the early AM with exacerbating symptomatology as the day progresses. Desiccating environmental factors may be implicated with symptom fluctuation.

While there have been European and American diagnostic criteria promulgated, in general dry mouth, dry eye and autoimmune disease constitute the diagnostic triad. The most comprehensive factors are decreased salivary flow, decreased lachrymal flow, lymphocyte glandular infiltration, the absence of nasal stimulated reflex tearing and the presence of serum antibodies.

Laboratory findings

Positive lip and lachrymal grand biopsy in conjunction with positive antinuclear antibody (ANA), rheumatoid factor (RF), anti-Ro (Sjögern specific A), and anti-La (Sjögern specific B) assist in establishing the diagnosis. Helper T cells are the predominant lymphocyte infiltrator along with B and CD4 lymphocytes. Epstein–Barr virus may play a role. An elevated IgG level has been shown to have a high specificity and positive predication value in predicting positive biopsy results.

TREATMENT

Systemic

Immunosuppressive agents such as cyclosporin A, trenonin, and corticosteroids have been utilized in severe cases. Oral bromhexine or pilocarpine has been advocate to improve lachrymal function.

Topical

The mainstay continues to be frequent application of tear substitutes (often non-preserved to avoid secondary irritation). For recurrent inflammation judicious use of topical steroids may be indicated. Existing tears may be conserved with punctual occlusion and the use of moist chamber goggles.

Cyclosporin A may have a role in increasing lachrymal function. Antibiotics may be necessary in secondary infection.

Other adjuncts

Hydrophilic bandage lenses, partial tarsorrhaphy, amniotic membranes have all been utilized with varying success. Controlling environmental humidification and airflow is helpful.

COMPLICATIONS

Secondary bacterial infection/ulceration and perforation can occur. The incidence of lymphoma in Sjögren’s is elevated.

Hydrops treatment involves the following:

●Discontinue contact lens wear;

●NaCl 5% drops and ointment;

●Patching;

●Some advocate short course of topical steroids;

●Cycloplegia for pain;

●Conservative follow up;

●Penetrating keratoplasty if edema does not resolve (uncommon) or visually significant scarring occurs (common).

For episodes of allergic reactions/atopy, the patient should be discouraged from rubbing the eyes; additional symptomatic treatment includes:

●Cold compresses;

●Antihistamine eyedrops or pills;

●Mast cell stabilizer eyedrops;

●Nonsteroidal anti-inflammatory drops.

202 LATTICE CORNEAL DYSTROPHY

371.54

(Lattice Dystrophy Type I, Lattice Dystrophy Type II, Lattice Dystrophy Type III, LCD-I, LCD-II, LCD-III,

Meretoja’s Syndrome, Biber-Haab- Dimmer Dystrophy, Familial Amyloid Polyneuropathy Type IV)

AND AVELLINO DYSTROPHY

371.54

Douglas L. Meier, MD

Portland, Oregon

Surgical

Penetrating keratoplasty is performed when the patient’s vision or tolerance of contact lenses deteriorates; there is a greater than 95% success rate. Corneal scarring and high keratometric values have been implicated as risk factors in progression of disease ultimately leading to corneal transplant. Postoperatively, many patients will still require contact lenses for best visual acuity, but the correction will usually be milder and well tolerated.

Lamellar keratectomy, either with a blade or excimer laser, can be used to remove raised superficial scars at the apex of the cone, which may improve contact lens tolerance. Lamellar keratoplasty is advantageous in that it avoids the problem of endothelial rejection, however, is technically very difficult and the final vision may be suboptimal.

Alternatives such as:

●Thermokeratoplasty;

●Epikeratoplasty;

●Intrastromal corneal ring segment implantation (Intacs) are used in special circumstances but rarely achieve as good a visual outcome as a full-thickness graft.

Lattice corneal dystrophy type I

ETIOLOGY

Lattice corneal dystrophy type I (LCD-I) is an autosomal dominant dystrophy that usually affects both eyes symmetrically. It is characterized by a localized corneal deposition of amyloid that is unrelated to systemic disease.

COURSE/PROGNOSIS

It appears in the first or second decade of life as characteristic refractile anterior stromal branching filamentous lines, focal white dots or dashes, or faint central stromal opacities. The deposits are prominent centrally and spare the peripheral 2 to 3 mm of cornea. The dystrophy is slowly progressive, with the lesions involving the deeper cornea and the opacity becoming denser and visually disabling, usually by the third or fourth decade. Occasionally, the first symptoms of the disease are noted in childhood or in the sixth or seventh decade; there is a considerable variation among affected family members in the age at which symptoms appear.

SUPPORT GROUP

National Keratoconus Foundation 733 Beverly Blvd., Suite 201

Los Angeles, CA 90048 www.nkcf.org

FAX (310) 360-9712 E-mail: info@nkcf.org

REFERENCES

Bron AJ: Keratoconus. Cornea 7:163–169, 1988.

Ihalainen A: Clinical and epidemiological features of keratoconus genetic and external factors in the pathogenesis of the disease. Acta Ophthalmol Suppl 178:1–64, 1986.

Kenney MC, Nesburn AB, Burgeson RE, et al: Abnormalities of the extracellular matrix in keratoconus corneas. Cornea 16:345–351, 1997.

Krachmer JH, Feder RS, Belin MW: Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol 28:293–322, 1984.

Rabinowitz YS: Keratoconus. Surv Ophthalmol 42:297–319, 1998.

Sray WA, Cohen EJ, Rapuano CJ, et al: Factors associated with the need for penetrating keratoplasty in keratoconus. Cornea 21:784–786, 2002.

DIAGNOSIS

Clinical signs and symptoms

Symptoms of photophobia, foreign body sensation, and pain from recurrent corneal epithelial erosions may be prominent in some patients. As corneal sensation decreases, the recurrent erosions become less painful. Irregular surface corneal astigmatism further decreases functional vision.

Laboratory findings

The characteristic histologic finding in the stroma is a fusiform deposit of amyloid that pushes aside the collagen lamellae, probably corresponding to the lattice lines and dots seen clinically. A degenerative pannus is seen with portions of Bowman’s membrane replaced by the deposits and irregular connective tissue. Clinically, these changes are associated with recurrent erosions. The stromal deposits stain orange-red with Congo red and demonstrate apple-green birefringence when viewed with polarized light. Red-green dichroism is seen with a green filter and a polarizing filter. Metachromasia can be demonstrated

The symptoms of Avellino dystrophy include foreign body sensation, photophobia, and pain, most likely from recurrent corneal epithelial erosions. In this respect, Avellino dystrophy is more like LCD-I (in which erosions are common) than granular corneal dystrophy (in which erosions are uncommon). There has been recurrence of the granular lesion in two of three patients who have had a penetrating keratoplasty for this condition.

Corneal changes are noted in the first decade of life as a diffuse clouding in central superficial stroma. With time these grayishwhite spots with blurry edges extend peripherally up to the limbus and into deeper stroma. Later, opacities become denser and can result in irregularity of the epithelium and in guttate appearance of Descemet’s membrane. Visual loss progresses to legal blindness by age 40 to 50.

REFERENCES

Chau HM, Ha NT, Cung LX, et al: H626R and R124C mutations of the TGFbI (bIGH3) gene caused lattice corneal dystrophy in Vietnamese people. Br J Ophthalmol 87:686–689, 2003.

Folberg R, Stone EM, Sheffield VC, et al: The relationship between granular, lattice type 1, and Avellino corneal dystrophies: a histopathologic study. Arch Ophthalmol 112:1080–1085, 1994.

Hayashida-Hibino S, Watanabe H, Nishida K, et al: The effect of TGF-B1 on differential gene expression profiles in human corneal epithelium studied by cDNA expression array. Invest Ophthalmol Vis Sc 42:1691– 1697, 2001.

Hida T, Tsubota K, Kigasawa K, et al: Clinical features of a newly recognized lattice corneal dystrophy. Am J Ophthalmol 104:241–248, 1987.

Hirano K, Hotta Y, Nakamura M, et al: Late-onset form of lattice corneal dystrophy caused by leu527Arg mutation of the TGFbI gene. Cornea 20:525–529, 2001.

Holland EJ, Daya SM, Stone EM, et al: Avellino corneal dystrophy: clinical manifestations and natural history. Ophthalmology 99:1564–1568, 1992.

Meisler DM, Fine M: Recurrence of the clinical signs of lattice corneal dystrophy (type I) in corneal transplants. Am J Ophthalmol 97:210– 214, 1984.

Meretoja J: Lattice corneal dystrophy-Two different types. Ophthalmologica 165:15–37, 1972.

Nassaralla BA, Garbus J, McDonnell PJ: Phototherapeutic keratectomy for granular and lattice corneal dystrophies at 1.5 to 4 years. J Refract Surg 12:795–800, 1996.

Rodrigues MM, Krachmer JH: Recent advances in corneal stromal dystrophies. Cornea 7:19–29, 1988.

Stock EL, Feder RS, O’Grady RB, et al: Lattice corneal dystrophy type IIIA: clinical and histopathologic correlations. Arch Ophthalmol 109:354– 358, 1991.

DIAGNOSIS

Clinical signs and symptoms

●Corneal findings include small, multiple, gray-white, pleomorphic opacities with irregular borders.

●The stroma is thinner than normal.

●Other clinical findings include loss of vision and photophobia.

●Endothelial decompensation and subsequent corneal edema can also occur.

Laboratory findings

●The gene for macular corneal dystrophy is a carbohydrate sulfotransferase gene (CHST6) on chromossome 16 (16q22).

●Histologically macular dsystrophy is characterized by the accumulation of glycosaminoglycans.

●Lesions stain with Alcian blue, colloidal iron and PAS.

●Serum or immunohistochemical evaluation of keratan sulfate (KS) can divide the dystrophy in type 1 (KS negative) or type 2 (KS positive).

TREATMENT

Ocular

●A contact lens may slightly improve vision by ‘smoothing’ the corneal surface.

Surgical

●Phototherapeutic keratectomy may help in early stages.

●Penetrating corneal transplantation is the treatment of choice (lamellar can be tried in selected cases).

203 MACULAR CORNEAL DYSTROPHY 371.55

(Groenouw’s Dystrophy Type II)

Alexandre S. Marcon, MD

Porto Alegre, Brazil

Italo M. Marcon, MD, PhD

Porto Alegre, Brazil

Edward J. Holland, MD

Cincinnati, Ohio

ETIOLOGY

Of the three classic stromal dystrophies (the other two are granular and lattice), macular dystrophy is the only autosomal recessive and the most severe.

COMPLICATIONS

●Graft rejection.

●Disease recurrence (with any form of treatment).

REFERENCES

Akova YA, Kirkness CM, McCartney ACE, et al: Recurrent macular corneal dystrophy following penetrating keratoplasty. Eye 4:698–705, 1990.

Aldave AJ, Yellore VS, Thonar EJ, et al: Novel mutations in the carbohydrate sulfotransferase gene (CHST6) in american patients with macular corneal dystrophy. Am J Ophthalmol 137(3):465–473, 2004.

Klintworth GK, Vogel FS: Macular corneal dystrophy: an inherited acid mucopolysaccharide storage disease of the corneal fibroblast. Am J Pathol 45:565–586, 1964.

Marcon AS, Cohen EJ, Rapuano CJ, et al: Recurrence of corneal stromal dystrophies after penetrating keratoplasty. Cornea 22(1):19–21, 2003.

Morgan G: Macular dystrophy of the cornea. Brit J Ophthal 50:57–67, 1966.

204 MOOREN’S ULCER 370.07

(Chronic Serpiginous Ulcer of the

Cornea, Ulcus Rodens)

Steven E. Wilson, MD

Cleveland, Ohio

Marcelo V. Netto, MD

Cleveland Ohio

COURSE/PROGNOSIS

Mooren’s ulcer typically begins with patchy stromal infiltrates in the periphery of the cornea. Most patients have moderate to severe pain associated with the infiltration and epithelial defects that may occur. As the disease progresses, the infiltrates usually coalesce and stromal tissue breakdown results in the formation of peri-limbal marginal ulceration. Over time the ulceration may extend for 360 degrees and progress centrally to involve the mid-peripheral and central cornea. Other ocular conditions such as episcleritis, scleritis, and iritis may be associated with the corneal ulcers in some patients.

ETIOLOGY/INCIDENCE

Mooren’s ulcer is a chronic, painful, and progressive disorder of the cornea, which often is bilateral and commonly leads to severe vision loss or even loss of the eye. Ulceration and tissue destruction are initially confined to the periphery of the cornea, but may progress in some patients to involve the entire cornea. There is usually undermining and infiltration of the leading edge of the circumferential peri-limbal ulceration. The cornea often becomes thinned and opacified by vascularization as the disease progresses. Although various forms of treatment have been proposed, some cases are refractory to all forms of therapy.

The etiology of this disease remains uncertain in the majority of cases, although autoimmunity has been suggested to play a role in the pathophysiology of the disease based on reports of cell-mediated and humoral responses to Bowman’s membrane, stromal and epithelial antigens, or even molecular mimicry responses against foreign antigens that resemble those in the cornea. Importantly, some patients have been identified who have an underlying chronic hepatitis due to hepatitis C virus infection and this should be excluded in every patient because it alters therapy and the potential outcome of treatment (Figure 204.1). The majority of cases, however, appear to be idiopathic. In these patients the disorder is a diagnosis of exclusion. Some other conditions that have been associated with Mooren’s ulcer include trauma, alkali burns, herpes zoster, herpes simplex, parasitic infections, and cataract and corneal surgery.

DIAGNOSIS

The diagnosis is one of exclusion that requires an extensive search for an occult and potentially lethal connective tissue disease. A thorough review of systems and a medical examination are mandatory. Laboratory investigation includes a complete blood cell count with differential, erythrocyte sedimentation rate, rheumatoid factor, complement fixation, antinuclear antibodies, antineutrophil cytoplasmic antibody, circulating immune complexes, liver function tests, treponemal antibody absorption test, blood urea nitrogen and creatinine, serum electrophoresis, urinalysis, and chest radiograph. In addition, testing for chronic hepatitis C infection should be done. HCV antibodies are detected using EIA test and if these are present, supplemental testing with Western blotting or HCV-RNA detection can positively confirm infection. Many of these patients are asymptomatic from a systemic point of view and have minimal or no increases in blood liver enzymes. If there is a high index of suspicion, then a liver specialist should be consulted for possible biopsy to rule out chronic hepatitis

Differential diagnosis

●Infectious peripheral corneal ulcerations (Staphylococcus aureus, Haemophilus influenzae, Moraxella spp., herpetic, fungal).

●Peripheral corneal degenerations (Terrien’s marginal degeneration, pellucid degeneration).

●Immune peripheral corneal infiltrates (staphylococcal marginal keratitis, acne rosacea, tuberculosis).

●Systemic autoimmune diseases (Wegener’s granulomatosis, polyarteritis nodosa rheumatoid arthritis, systemic lupus erythematosus, relapsing polychondritis, Sjögren’s syndrome, inflammatory bowel disease, a1-antitrypsin deficiency). Some of these conditions are life-threatening and must be excluded by consultation with other specialists.

FIGURE 204.1. Hepatitis C virus-associated Mooren’s like ulcer prior to treatment. The contralateral eye had similar marginal ulceration with undermining of the leading edge. (Reprinted by permission from Wilson SE, Lee WM, Murakami C, et al: Mooren’s-type hepatitis C virus (HCV)-associated corneal ulceration. Ophthalmology 101:736– 745, 1994.)

TREATMENT

The treatment of Mooren’s ulcer is often unsatisfactory, especially the bilateral aggressive form. The goal of therapy is to arrest the progression of the ulcerative keratitis and to reepithelialize the cornea.

Systemic

In cases in which underlying chronic hepatitis C virus (HCV) infection is confirmed, systemic treatment with interferon alpha, marketed as Intron A by Schering Corp. and Roferon-A