Posterior Polymorphous Corneal Dystrophy

First described by Koeppe, posterior polymorphous corneal dystrophy (PPMD) is a dominantly inherited condition characterized by particular alterations of the Descemet membrane and the corneal endothelium.[1] Typically, the corneal changes are either slowly progressive or nonprogressive. In severe cases, corneal decompensation and edema can occur. Although PPMD is most often a bilateral condition, marked asymmetry in the degree of involvement may be seen. Most persons with PPMD are asymptomatic. 

Three main abnormalities are described: vesicular changes, endothelial band lesions, and irregular diffuse opacities of the posterior corneal surface involving both the Descemet membrane and the endothelium. The corneal endothelium undergoes a transformation and demonstrates many epithelial characteristics on examination with electron microscopy and immunohistochemical analysis. Often, the endothelium is found to be multilayered. Most patients exhibit vesicular lesions, which are the hallmark of PPMD.

Frequency

United States

The frequency of PPMD is not well documented. Although it is considered to be uncommon, PPMD may be recognized and diagnosed more often in recent years than in the past.

International

Liskova et al found that the prevalence of PPCD in the Czech Republic appears to be the highest worldwide.[2]

Mortality/Morbidity

The effect of PPMD on patients is highly variable, with a broad clinical spectrum of findings, ranging from nonprogressive asymptomatic disease to progressive or advanced debilitating corneal disease with corneal decompensation and glaucoma.

Race

No racial predilection exists.

Sex

No sexual predilection exists.

Age

Although PPMD is an autosomal dominantly inherited corneal dystrophy, the age at diagnosis is highly variable because of the broad spectrum of disease severity. Findings may be present at birth. Most patients are first identified at age 30-50 years; however, this is likely only indicative of a more common age for ocular examinations.

Some patients may present at birth with congenital disease, exhibiting advanced disease with corneal edema.

Presentation in adulthood is indicative of a more stable disease state with a decreased probability of progression to corneal decompensation.

Most patients with significant symptoms present at age 25-50 years.

The clinical findings in patients with PPMD are highly variable, with a broad clinical spectrum of findings, ranging from only occasional Descemet membrane vesicles to progressive debilitating corneal disease with corneal decompensation and glaucoma.

A family history of PPMD should be assessed.

Although most patients with PPMD are asymptomatic, the most common symptoms in those with more significant involvement are as follows:

• Photophobia

• Decreased visual acuity

• Foreign body sensation

The most characteristic finding on slit lamp biomicroscopy is multiple vesicles or blisters, either isolated or grouped in clusters, on the posterior corneal surface. The vesicles often have identifiable surrounding grayish halos. These are often at the level of Descemet membrane and the endothelium, but they can also be seen in the posterior stroma.

Slit lamp biomicroscopy may identify all or some of the following characteristics depending on the extent of the disease:

• Posterior corneal opacities occurring in linear bands or other polymorphous configurations with irregular scalloped edges[3]

• Areas of more diffuse posterior corneal opacities

• Focal excrescents of the Descemet membrane

• Iridocorneal adhesions

• Pupillary ectropion

• Corectopia

• Stromal and epithelial edema (advanced cases)

• Corneal guttae

• Iridocorneal adhesions (peripheral anterior synechiae)

• Increased intraocular pressure

The precise etiology of PPMD remains unknown. PPMD is a congenital inherited dystrophy involving abnormalities of the corneal endothelium and the Descemet membrane.[4, 5]

Most cases of PPMD are transmitted in an autosomal dominant fashion with variable expression, although autosomal recessive transmission has also been reported.[6]

A number of autosomal dominant cases of PPMD have been linked to a mutation in an unidentified gene located at band 20q11, whereas other cases have reported a mutation in a gene encoding for collagen VIII located on chromosome 1 (COL8A2) as the cause of PPMD.

In other cases, the genetic locus remains unknown.

PPMD has been associated with other conditions, including the following:

• Alport syndrome

• Keratoconus

No lab studies are available.

Specular microscopy has proven to be valuable in identifying the characteristic vesicular changes of the Descemet membrane in patients with PPMD. Typically, the endothelial cell count is only mildly diminished with varying amounts of polymegethism and pleomorphism.

Confocal microscopy has also been used to identify the typical features of PPMD.[7, 8]

On most occasions, PPMD can be clinically diagnosed using slit lamp examination; however, mild cases may require further imaging studies to confirm the diagnosis.

Tonometry is used to measure intraocular pressure, which may be elevated in up to 40% of patients with PPMD.

The secondary open-angle glaucoma that occurs in some patients with PPMD is believed to be due to an abnormality of the trabecular endothelium.

Examination of family members may also be helpful in making the diagnosis.

Light microscopy typically demonstrates 4 types of cells: normal endothelial cells, degenerated endothelial cells, fibroblast-like cells, and epithelial-like cells. In 60% of cases, a multilayered endothelium can be identified that has many characteristics similar to that of the epithelium. Immunohistochemical studies have also shown positive staining of the endothelium using epithelial cell markers.

Scanning electron microscopy and transmission electron microscopy of corneal tissue show lamination of the Descemet membrane, fibroblast-like endothelial cells, and microvilli characteristic of epithelial transformation of the corneal endothelium.

No formal staging system has been described for PPMD.

Management of PPMD varies widely based on the differences in severity of corneal decompensation. Many patients who are asymptomatic and show minimal signs of PPMD can be treated conservatively and do not require therapy.

Ruptured corneal bullae should be treated similar to a corneal abrasion.

Hyperosmotic saline drops and ointments may be used in cases of corneal failure with corneal edema.

Secondary glaucoma may require medical or surgical management.

A bandage soft contact lens may be used as a temporary measure to treat bullous keratopathy.

Future considerations:   As is the case for many genetic conditions, the CRISPR/Cas system may eventually help those afflicted with this condition.  The CRISPR/Cas system offers a broad scope of gene editing and engineering to correct underlying genetic causes in corneal dystrophies. Corneal tissue--specific gene correction in vitro with minimal off-target effects and optimal gene correction efficiency followed by their successful surgical implantation, or in vivo CRISPR administration targeting pathogenic genes finds a way to explore therapeutic intervention for corneal dystrophies. (footnote  #30 - Asia-Pacific Journal of Ophthalmology 11(4):p 346-359, July/August 2022. )

 

The risk factors for more advanced disease, requiring surgery, include increased intraocular pressure and iridocorneal adhesions.

Corneal transplantation is usually reserved for patients with substantially decreased visual acuity or when the disease is advanced and painful due to ruptured epithelial bullae. Penetrating keratoplasty (full thickness corneal transplantation) has been the transplant procedure of choice in the past. The newer techniques of posterior endothelial keratoplasty, such as Descemet membrane stripping endothelial keratoplasty (DSEK) and Descemet membrane endothelial keratoplasty (DMEK), have been shown to be successful.[9, 10]

Rare cases of corneal graft failure due to recurrence of PPMD in the donor graft have been reported, but the most common problem following a corneal transplant is related to uncontrolled glaucoma.[11]

To treat pain in eyes without good visual potential, other procedures, such as anterior stromal micropuncture, excimer laser phototherapeutic keratectomy, amniotic membrane transplantation, and conjunctival flap surgery, can also be considered.

When glaucoma medications no longer adequately control the intraocular pressure, glaucoma laser or incisional surgery may be required to prevent glaucomatous optic nerve damage. Surgery with limited success is often seen in patients with peripheral anterior synechiae without gonioscopy and elevated intraocular pressure. Poor intraocular pressure control, even with surgical intervention, is observed.

Depending on the severity of the condition, consultation with corneal and glaucoma subspecialists may be warranted.

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Class Summary

Sodium chloride hypertonic ophthalmic solutions are used to dehydrate the cornea.

Sodium chloride hypertonic, ophthalmic (Muro 128 Ophthalmic)

Used for temporary relief of corneal edema. Available as 2% and 5% ophthalmic solution concentrations and 5% ointment.

The frequency of follow-up care for patients with PPMD depends on the severity of disease.

Corneal erosion, secondary corneal ulcers, corneal scarring, graft rejection, endothelial failure, and other complications can occur and lead to corneal graft failure.

Glaucoma can be present prior to corneal transplantation or may result from corneal transplantation.

The prognosis is generally dependent on the severity of disease. In most cases, PPMD is a slowly progressive or nonprogressive disease. Patients with mild disease that is identified in adulthood have the best prognosis and are unlikely to require penetrating keratoplasty during their lifetime.