Posterior Polymorphous Corneal Dystrophy


Article Author:
Christian Guier
Bhupendra Patel
Gerhard Cibis


Article Editor:
Arun Gulani


Editors In Chief:
Shane Havens
Jim Wang
Koushik Tripathy


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
11/11/2019 2:52:56 PM

Introduction

The term "dystrophia" is derived prefix "dys" meaning "bad or difficult" and “trephein” meaning “to nourish” or interpreted more correctly here as “metabolism.” It is a genetic defect at the cellular level. Corneal dystrophies are the clinical result of abnormal cellular metabolism. All cells in the various layers of corneal anatomy from epithelium to stroma to endothelium are afflicted in different ways, leading to the multitude of specific clinical entities rooted in a specific cell line. [1][2][3]

In posterior polymorphous corneal dystrophy (PPCD), the corneal endothelium manifests an epithelial morphology producing an aberrant basement membrane. The normal Descemet basement membrane laid down by endothelial cells is abnormally variably thickened in posterior polymorphous corneal dystrophy (PPMD). This accounts for the classic “surface of the moon” appearance seen on slit lamp retro-illumination.[4][5]

PPCD was first described by Koeppe, and it is inherited dominantly and is characterized by alterations of the Descemet membrane and the corneal endothelium. The corneal changes are either nonprogressive or slowly progressive. In severe cases, edema and corneal decompensation can occur. Although PPMD may be a bilateral condition, marked asymmetry in the degree of involvement may be seen. Most persons with PPMD are asymptomatic.[6][7]

Etiology

Rather than properly and strictly confining themselves to the posterior surface of the cornea, the epithelialized PPMD endothelial cells can migrate randomly and erratically across the chamber angle onto the peripheral iris surface, secreting the abnormal basement membrane. On the iris surface, this membrane leads to corectopia and pupillary ectropion. Areas of posterior synechiae with segmental sections of angle closure occur, increasing the risk for glaucoma.

The dystrophic endothelial cells are inefficient in their normal task of pumping fluid out of the corneal stroma. Stromal and epithelial corneal edema may occur diffusely or sectorally even with intraocular pressures in a normal to near normal range and vary diurnally accounting for a confusing variance in photophobic complaints about time.[8][9][10]

Epidemiology

Several genetic mutations have been identified as causing PPMD.

  • PPCD1 is thought to result from a heterozygous mutation in the promoter of the OVOL2 gene (616441) on chromosome 20p11.
  • PPCD2 (609140) is a mutation in the COL8A2 gene (120252) on chromosome 1p34.3.
  • PPCD3 (609141) mutation in the ZEB1 gene (189909) on chromosome 10p.

PPMD also has been associated with other conditions such as Alport syndrome and keratoconus.

Pathophysiology

The thickened, abnormal Descemet and stromal edema may cause pseudo-elevation of intraocular applanation tensions. The condition manifests as highly variable, even in members of the same family. It is often asymptomatic for life with varying degrees of photophobia or none. At any time later in life, depending on the progression of the disease, patients may develop photophobia, decreasing vision, and sectorial corneal clouding. Because of the inefficiency of fluid extraction from the stroma diurnal variations in corneal edema occur even with normal or modestly low-pressure elevations. True glaucoma from angle closure may occur at any stage of life including present at birth.

Histopathology

Light microscopy demonstrates normal endothelial, degenerated endothelial, fibroblast-like, and epithelial-like cells. 

  • A multilayered endothelium may be identified that has many characteristics similar to that of the epithelium. 
  • Immunohistochemical studies have shown positive staining of the endothelium using epithelial cell markers.
  • Scanning electron and transmission electron microscopy of corneal tissue demonstrates lamination of the Descemet membrane, fibroblast-like endothelial cells, and microvilli that are characteristic of the epithelial transformation of the corneal endothelium.

History and Physical

PPMD band edges are two not perfectly parallel and undulate with their variable thickness being a random buildup of the basement membrane. Lack of megalocornea in the face of significant corneal edema and questionable pressure elevation should alert one to the condition. If not convincing on slit lamp examination of the patient cornea, such as when the epithelial edema is too dense to evaluate the stroma and endothelium, examination of the parents may reveal the dominant nature of inheritance establishing a suspected diagnosis. 

Penetrating keratoplasty (PK) has historically been successful. However, if corneal stroma and epithelium are not compromised, and iris synechiae do not interfere, Descemet membrane endothelial keratoplasty (DMEK) can be considered.

The characteristic finding on slit lamp biomicroscopy is multiple vesicles, either isolated or grouped in clusters, found on the posterior corneal surface.

The vesicles usually have identifiable grayish halos.

The vesicles are often at the level of the endothelium and Descemet membrane, but they may also be seen in the posterior stroma.

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

  • The vesicles usually have identifiable grayish halos.
  • The vesicles are often at the level of the endothelium and Descemet membrane, but they also may be seen in the posterior stroma.

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

  • Areas of more diffuse posterior corneal opacities
  • Corectopia
  • Corneal guttae
  • Focal excrescents of the Descemet membrane
  • Iridocorneal adhesions
  • Iridocorneal adhesions with peripheral anterior synechiae
  • Increased intraocular pressure
  • Posterior corneal opacities occur in linear bands or other polymorphous configurations with irregular, scalloped edges
  • Pupillary ectropion
  • Stromal and epithelial edema seen in advanced cases

Evaluation

Evaluation requires a slit lamp, and retroillumination will give the most immediate information.

  • Specular microscopy has proven to be valuable in identifying the characteristic vesicular changes of the Descemet membrane in patients with PPMD.
  • The endothelial cell count is mildly diminished with varying amounts of polymegethism and pleomorphism.
  • Confocal microscopy also has been used to identify the typical features.
  • PPMD can be diagnosed using slit-lamp examination; however, mild cases require imaging studies to confirm the diagnosis.
  • Tonometry is used to measure intraocular pressure, which may be elevated in 40% of patients with PPMD.
  • The secondary open-angle glaucoma that occurs in patients with PPMD is believed to be due to abnormalities of the trabecular endothelium.
  • Examination of family members may be helpful in making the diagnosis.

Treatment / Management

Penetrating Keratoplasty (PK) has historically been successful. However, if corneal stroma and epithelium are not compromised, and iris synechiae do not interfere, DMEK can be considered.

Differential Diagnosis

The differential diagnoses includes:

  • Fuchs Endothelial Dystrophy
  • Primary Congenital Glaucoma

Staging

No formal staging system has been described for PPCD.

Prognosis

The prognosis is dependent on the severity of the disease.

  • PPCD is a slow, nonprogressive or slowly progressive disease in most cases.
  • Patients with mild disease that are identified in adulthood have a good prognosis and are not likely to require PK.
  • The frequency of follow-up needed is dependant on the severity of the disease.
  • Corneal erosion, secondary corneal ulcers, graft rejection, corneal scarring, and endothelial failure can occur and can result in corneal graft failure and a poorer prognosis.

Enhancing Healthcare Team Outcomes

PPCD is best managed by an ophthalmologist.  Penetrating Keratoplasty (PK) has historically been successful. However, if corneal stroma and epithelium are not compromised, and iris synechiae do not interfere, DMEK can be considered.

The prognosis for most patients is good.


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Posterior Polymorphous Corneal Dystrophy - References

References

Sorkin N,Einan-Lifshitz A,Boutin T,Showail M,Borovik A,Chan CC,Rootman DS, Descemet membrane endothelial keratoplasty in iridocorneal endothelial syndrome and posterior polymorphous corneal dystrophy. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie. 2019 Apr;     [PubMed]
Dudakova L,Skalicka P,Davidson AE,Liskova P, Coincidental Occurrence of Schnyder Corneal Dystrophy and Posterior Polymorphous Corneal Dystrophy Type 3. Cornea. 2019 Jun;     [PubMed]
Dudakova L,Evans CJ,Pontikos N,Hafford-Tear NJ,Malinka F,Skalicka P,Horinek A,Munier FL,Voide N,Studeny P,Vanikova L,Kubena T,Rojas Lopez KE,Davidson AE,Hardcastle AJ,Tuft SJ,Liskova P, The utility of massively parallel sequencing for posterior polymorphous corneal dystrophy type 3 molecular diagnosis. Experimental eye research. 2019 May;     [PubMed]
Litke AM,Samuelson S,Delaney KR,Sauvé Y,Chow RL, Investigating the Pathogenicity of VSX1 Missense Mutations and Their Association With Corneal Disease. Investigative ophthalmology     [PubMed]
Asselineau K,Robert PY,Janulevičienė I, Clinical findings observed by in-vivo confocal microscopy of posterior polymorphous corneal dystrophy. Journal francais d'ophtalmologie. 2018 Sep;     [PubMed]
Noguchi A,Okumura N,Sotozono C,Kinoshita S, Effect of Posterior Corneal Vesicles on Corneal Endothelial Cell Density and Anisometropic Amblyopia. Cornea. 2018 Jul;     [PubMed]
Zakharevich M,Kattan JM,Chen JL,Lin BR,Cervantes AE,Chung DD,Frausto RF,Aldave AJ, Elucidating the molecular basis of PPCD: Effects of decreased ZEB1 expression on corneal endothelial cell function. Molecular vision. 2017;     [PubMed]
Stadnikova A,Dudakova L,Skalicka P,Valenta Z,Filipec M,Jirsova K, Active transforming growth factor-β2 in the aqueous humor of posterior polymorphous corneal dystrophy patients. PloS one. 2017;     [PubMed]
Zaarour K,Slim E,Antoun J,Waked N, Thick keratoconic cornea associated with posterior polymorphous corneal dystrophy. Journal francais d'ophtalmologie. 2017 Mar;     [PubMed]
Ahn YJ,Choi SI,Yum HR,Shin SY,Park SH, Clinical Features in Children with Posterior Polymorphous Corneal Dystrophy. Optometry and vision science : official publication of the American Academy of Optometry. 2017 Apr;     [PubMed]

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