Figure 10-5 Gelatinous droplike corneal dystrophy. A, Mulberry type. B, Band keratopathy type. C, Kumquat-like type.

(Reproduced with permission from Weiss JS, Møller H, Lisch W, et al. The IC3D classification of the corneal dystrophies. Cornea. 2008;27(10:Suppl 2):S11.)

MANAGEMENT Recurrence within a few years is seen in all patients following superficial keratectomy, lamellar keratoplasty (LK), or penetrating keratoplasty (PK). Soft contact lenses are effective in managing the abnormal epithelial permeability to decrease recurrences.

Ide T, Nishida K, Maeda N, et al. A spectrum of clinical manifestations of gelatinous droplike corneal dystrophy in Japan. Am J Ophthalmol. 2004;137(6):1081–1084.

Kinoshita S, Nishida K, Dota A, et al. Epithelial barrier function and ultrastructure of gelatinous drop-like corneal dystrophy. Cornea. 2000;19(4):551–555.

Bowman Layer Corneal Dystrophies

Reis-Bücklers corneal dystrophy (RBCD)

Alternative names Corneal dystrophy of Bowman layer type 1 (CDB1), geographic corneal dystrophy, superficial granular corneal dystrophy, atypical granular corneal dystrophy, granular corneal dystrophy type 3, anterior limiting membrane dystrophy type 1 (ALMD1)

Inheritance Autosomal dominant

PATHOLOGY On light microscopy, the Bowman layer is disrupted or absent and replaced by a sheetlike connective tissue layer with granular Masson trichrome-red deposits. Transmission electron microscopy shows electron-dense, rod-shaped bodies. The rod-shaped bodies are immunopositive for the TGFBI protein keratoepithelin. Electron microscopy is needed to histologically distinguish RBCD from Thiel-Behnke corneal dystrophy, which has curly fibers (see the next section). On

dystrophy, anterior limiting membrane dystrophy type 2 (ALMD2), curly fibers corneal dystrophy, Waardenburg-Jonkers corneal dystrophy

Inheritance Autosomal dominant

PATHOLOGY Light microscopy shows thickening of the epithelial layer, which allows for ridges and furrows in the underlying stroma and focal absences of the epithelial basement membrane. The Bowman layer is replaced by fibrocellular material in a pathognomonic wavy, “saw-toothed” pattern. On electron microscopy, curly fibers (9–15 nm) distinguish this dystrophy from RBCD. These curly fibers are immunopositive for the TGFBI protein keratoepithelin associated with the 5q31 genetic locus. On confocal microscopy, distinct deposits are found in the epithelium and Bowman layer. The deposits in the basal epithelial cell layer show reflectivity, with round edges and dark shadows. The Bowman layer is replaced with irregular reflective material that is less reflective than in RBCD.

CLINICAL FINDINGS Onset is in the first or second decade of life, with symmetric subepithelial reticular (honeycomb) opacities, sparing the peripheral cornea (Fig 10-7). Opacities may progress to deep stromal layers and corneal periphery. Clinically distinguishing TBCD from RBCD is difficult. Recurrent erosions cause ocular discomfort and pain, with worsening of vision from corneal opacification. Erosions in TBCD are less frequent and severe than those with RBCD. Vision decreases secondary to increased corneal opacification.

Figure 10-7 The symmetric subepithelial reticular (honeycomb) opacities of Thiel-Behnke corneal dystrophy. (Reproduced with

permission from Weiss JS, Møller H, Lisch W, et al. The IC3D classification of the corneal dystrophies. Cornea. 2008;27(10:Suppl 2):S13.)

MANAGEMENT Management is similar to that used in RBCD.

Kobayashi A, Sugiyama K. In vivo laser confocal microscopy findings for Bowman’s layer dystrophies (Thiel-Behnke and ReisBücklers corneal dystrophies). Ophthalmology. 2007;114(1):69–75.

Küchle M, Green WR, Völcker HE, Barraquer J. Reevaluation 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. 1995;14(4):333–354.

Stromal Corneal Dystrophies: TGFBI Dystrophies

Table 10-4 provides information on the histologic identification of the classic stromal corneal

dystrophies.

Table 10-4

Lattice corneal dystrophy (LCD): classic lattice corneal dystrophy (LCD1) and variants (the variants are multiple subtypes of lattice, which are not described here)

Alternative names Classic LCD, LCD type 1, Biber-Haab-Dimmer

Inheritance Autosomal dominant

PATHOLOGY Light microscopy of lattice dystrophy shows amyloid deposits concentrated most heavily in the anterior stroma. Amyloid may also accumulate in the subepithelial area, giving rise to poor epithelial–stromal adhesion. Epithelial atrophy and disruption, with degeneration of basal epithelial cells, and focal thinning or absence of the Bowman layer increase progressively with age. An eosinophilic layer between the epithelial basement membrane and Bowman layer develops, with stromal deposition of the amyloid substance distorting the corneal lamellar architecture. Amyloid stains rose to orange-red with Congo red dye and metachromatically with crystal violet dye, and it exhibits dichroism and birefringence. Electron microscopy reveals extracellular masses of fine 8–10- μm fibrils that are electrondense and randomly aligned. In vivo confocal microscopy reveals characteristic linear images that should be differentiated from those seen in infection with fungal hyphae. Corneal deposits caused by monoclonal gammopathy may resemble lattice lines.

CLINICAL FINDINGS Lattice dystrophy is relatively common and is characterized by glasslike branching lines in the stroma. The spectrum of corneal changes is broad, and the classic branching lattice figures may not be present in all cases. Refractile lines, central and subepithelial ovoid white dots, and diffuse anterior stromal haze appear early in life. The refractile lines, so-called lattice lines, are best seen against a red reflex or with retroillumination (Fig 10-8). These lines start centrally and superficially and spread centrifugally and deeper. The stroma can take on a ground-glass appearance, but the peripheral cornea remains clear. Recurrent epithelial erosions occur often. Stromal haze and epithelial surface irregularity may decrease vision.

Figure 10-8 Lattice corneal dystrophy. (Courtesy of Vincent P. deLuise, MD.)

MANAGEMENT Recurrent erosions are managed with therapeutic contact lenses, superficial keratectomy, or PTK. Severe cases of lattice dystrophy with vision loss are treated with deep anterior lamellar keratoplasty (DALK) or PK. Recurrence of this dystrophy may occur in the corneal graft. It is thought that lattice dystrophy recurs more frequently after grafting than does granular or macular dystrophy. One study suggested that granular dystrophy recurred more often than lattice; the study, however, had a 5-year follow-up; the mean time of recurrence for lattice is 9 years (range, 3–26 years).

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

Pradhan MA, Henderson RA, Patel D, McGhee CN, Vincent AL. Heavy chain amyloidosis in TGFBI-negative and Gelsolinnegative atypical lattice corneal dystrophy. Cornea. 2011;30(10):1163–1166.

Lattice corneal dystrophy (LCD): gelsolin type (LCD2)

Alternative names Familial amyloidosis, Finnish type (FAF); Meretoja syndrome; amyloidosis V; familial amyloid polyneuropathy type IV (FAP-IV)

Inheritance Autosomal dominant

PATHOLOGY Light microscopy shows amyloid in the lattice lines as a discontinuous band under the Bowman layer and within the sclera. The amyloid in this condition is related to gelsolin and does not stain for type AA or AP. The mutated gelsolin is seen deposited in the conjunctiva, sclera, and ciliary body, along the choriocapillaris, in the ciliary nerves and vessels, and in the optic nerve. Extraocularly, amyloid is detected in arterial walls, peripheral nerves, and glomeruli. On confocal microscopy, deposits are seen along the basal epithelial cells and stromal nerves.

CLINICAL FINDINGS This form of LCD combines lattice corneal changes with coexisting systemic amyloidosis and presents in the third to fourth decade of life. Patients have a characteristic facial mask; dermatochalasis; lagophthalmos; pendulous ears; cranial and peripheral nerve palsies; and dry, lax skin with amyloid deposition (Fig 10-9). The risk of open-angle glaucoma may be increased. The classic corneal lattice lines are less numerous and more peripheral, and they spread centripetally from the limbus. The central cornea is relatively spared; corneal sensation is reduced. Dry eye and recurrent erosions may occur late in life.

Figure 10-9 A, Diffuse lattice lines in lattice corneal dystrophy, gelsolin type (Meretoja). B, Typical facies of the Meretoja

syndrome. (Reproduced with permission from Weiss JS, Møller H, Lisch W, et al. The IC3D classification of the corneal dystrophies. Cornea. 2008;27(10:Suppl 2):S16.)

Granular corneal dystrophy type 1 (GCD1)

Alternative names Groenouw corneal dystrophy type I

Inheritance Autosomal dominant

PATHOLOGY Microscopically, the granular material is hyaline and stains bright red with Masson trichrome stain. An electron-dense material made up of rod-shaped bodies immersed in an amorphous matrix is seen on electron microscopy. Histochemically, the deposits are noncollagenous protein that may derive from the corneal epithelium and/ or keratocytes. Hyperreflective opacities are seen on confocal microscopy. Although the exact cause is unknown, a mutation different from that of RBCD, LCD1, and GCD2 has been identified in the TGFBI gene on chromosome 5q31, which is responsible for the formation of keratoepithelin.

CLINICAL FINDINGS Onset occurs early in life with crumblike opacities in the superficial cornea. On direct illumination, the opacities appear white; however, indirect illumination reveals small translucent dots with vacuoles and a glassy splinter or “crushed bread crumb” appearance. The lesions do not extend to the limbus but can extend anteriorly through focal breaks in the Bowman layer (Fig 10-10). The dystrophy is slowly progressive, with most patients maintaining good vision and visual acuity only rarely dropping to 20/200 after age 50. Patients report glare and photophobia. Recurrent erosions occur and vision decreases as the opacities become more confluent.

Figure 10-10 Granular dystrophy type 1.

MANAGEMENT Early in the disease process, no treatment is needed. Recurrent erosions may be treated with therapeutic contact lenses and superficial keratectomy. PTK may work transiently. When vision is affected, DALK or PK has a good prognosis. Recurrence in the graft (anteriorly and peripherally) may occur after many years as fine subepithelial opacities varying from the original presentation.

Granular corneal dystrophy type 2 (granular-lattice) (GCD2)