Pellucid Marginal Degeneration (PMD) 

Updated: Oct 30, 2017
Author: Jean Deschênes, MD, FRCSC; Chief Editor: Hampton Roy, Sr, MD 

Overview

Background

Pellucid marginal degeneration (PMD) is a bilateral, noninflammatory, peripheral corneal thinning disorder characterized by a peripheral band of thinning of the inferior cornea. The cornea in and adjacent to the thinned area is ectatic. Schalaeppi first coined the term pellucid marginal degeneration in 1957.

Pathophysiology

The etiology of pellucid marginal degeneration has not been clearly established, but collagen abnormalities, as seen in keratoconus, have been reported. The thinned and presumably weakened cornea may protrude as a result of the positive intraocular pressure.

Epidemiology

Frequency

United States

Pellucid marginal degeneration is rare, and the exact incidence and prevalence are unknown. However, the incidence may be considerably underestimated, as this condition is often misdiagnosed as keratoconus.

Mortality/Morbidity

Deterioration of visual function results from the irregular astigmatism induced by asymmetric distortion of the cornea. The deterioration in visual function is commonly severe.

Refractive surgery, such as photorefractive keratectomy (PRK), can cause severe corneal haze, and results with laser-assisted in situ keratomileusis (LASIK) are unpredictable.

Race

No racial preponderance has been identified for pellucid marginal degeneration.

Sex

There are controversies concerning the sexual predilection of pellucid marginal degeneration. Some studies have reported no difference,[1, 2] while others have reported a male predilection.[3, 4, 5] In a 2016 Japanese study of 162 eyes with pellucid marginal degeneration, 75% of the patients were men.[6]

Age

Patients are usually aged 20-40 years at the time of clinical presentation.

Prognosis

The affected cornea maintains its clarity. However, patients experience progressive deterioration of vision due to irregular astigmatism.[6] The prognosis of pellucid marginal degeneration is clinical.

 

Presentation

History

Pellucid marginal degeneration (PMD) is usually asymptomatic, except for the progressive deterioration in uncorrected and spectacle corrected visual acuity caused by the irregular astigmatism induced by the corneal ectasia.

The increased corneal higher-order aberrations (HOAs), especially the trefoil and spherical aberrations, are the leading causes of optical errors, along with the induced against-the-rule astigmatism and visual acuity decline.[7]

Episodes of corneal hydrops with resultant pain, as seen in keratoconus, have been reported, but they occur only rarely.[8]

Physical

Uncorrected visual acuity is often severely reduced. Visual acuity, as measured by using a pinhole, is close to normal. Refraction and keratometry show against-the-rule astigmatism. Visual acuity typically cannot be restored by using a spherocylindrical combination of lenses. Rigid gas permeable contact lenses are often required to treat pellucid marginal degeneration, but patients often experience glare and decreased contrast sensitivity despite achieving good Snellen acuity. It is unclear if this condition is due to the corneal disease or the contact lens wear.

Results of slit lamp examination are characterized by a peripheral band of thinning of the inferior cornea from the 4-o'clock position to the 8-o'clock position; this is shown in the image below.

Slit lamp image of the inferior cornea in a patien Slit lamp image of the inferior cornea in a patient with advanced pellucid marginal degeneration. Image illustrates inferior corneal thinning, a hallmark of this disease.

This thinning is accompanied by 1-2 mm of normal cornea between the limbus and the area of thinning. Corneal ectasia is most marked just central to the band of thinning. The central cornea is usually of normal thickness, and the epithelium overlying the area of thinning is intact.

Both eyes are usually affected, but the degree of involvement may be asymmetric. The area of thinning typically is epithelialized, clear, avascular, and without lipid deposits. Sporadic reports have described unilateral pellucid marginal degeneration,[9, 10] but a 2016 study suggested that this rate might be higher than previously recognized, precisely 25% in a cohort of 162 eyes with pellucid marginal degeneration.[6]

On careful slit lamp evaluation, prominent lymphatics often are detected at the inferior limbus parallel to the area of thinning. Vertical striations at the level of the Descemet membrane (similar to the Vogt striae) may be seen in rare instances.

Causes

The cause of pellucid marginal degeneration is unknown.

A study of 162 eyes with pellucid marginal degeneration suggested that patients with unilateral involvement might have a different disease background than those with bilateral disease. One-fifth of the patients with unilateral involvement had allergic disorders, such as atopic dermatitis, allergic rhinitis, and conjunctivitis.[3]

Relationship between pellucid marginal degeneration and keratoconus

Some cases of  PMD may overlap with keratoconus. In a 2016 study, 40% (7 of 17) of patients with unilateral PMD had either keratoconus or were suspected of having keratoconus in the contralateral eye.[6]

 

DDx

Diagnostic Considerations

Keratoconus 

Keratoconus is the major mimicker of pellucid marginal degeneration.

Similarities between PMD and keratoconus have been attributed to the absence of firm criteria for each disease entity.

Keratoglobus 

Keratoglobus causes generalized thinning of the cornea.

The thinning is most marked at the limbus, extending circumferentially for 360°.

The whole cornea protrudes, in contrast to the regional thinning seen in keratoconus and the inferior paralimbal thinning in pellucid marginal degeneration.

Terrien marginal degeneration

Terrien marginal degeneration affects an age group similar to that affected by pellucid marginal degeneration.

Terrien marginal degeneration can be bilateral.

Although this condition can be associated with large amounts of astigmatism, it can be differentiated from pellucid marginal degeneration because the superior cornea is predominantly affected and because the area of thinning is often associated with vascularization and lipid deposition.

Furrow degeneration

Furrow degeneration has some features of pellucid marginal degeneration.

An intact epithelium is present, and the area of corneal thinning is not vascularized, at least in the acute phase.

The differentiating feature is that the area of thinning is closer to the limbus with virtually no intervening zone of normal cornea, unlike the findings in pellucid marginal degeneration.

Furrow degeneration occasionally involves the superior cornea, and an associated adjacent area of scleritis may be present.

Edges of the furrow are steeper than the gradual attenuation seen in pellucid marginal degeneration.

Furrow degeneration occurs adjacent to the lipid deposition in arcus senilis, which is typically observed in elderly patients.

Peripheral corneal melting disorders

Peripheral corneal melting disorders, such as Mooren ulcer, or peripheral melting secondary to rheumatologic disorders are characterized by pain.

This pain may be severe in cases of Mooren ulcer.

Associated findings include an epithelial defect over the area of thinning and corneal vascularization adjacent to the area of thinning in the acute phase.

Contact lens–induced warping of the cornea

Contact lens–induced warping of the cornea can mimic the appearance of pellucid marginal degeneration on corneal topography.

Differential Diagnoses

  • Contact Lens Complications

  • Furrow degeneration

  • Keratoconus

  • Keratoglobus

  • Mooren ulcer

  • Terrien marginal degeneration

 

Workup

Imaging Studies

Optical coherence tomography (OCT) and Scheimpflug-based corneal imaging systems can illustrate inferior corneal thinning (see image below).

Optical coherence tomography (OCT) of cornea with Optical coherence tomography (OCT) of cornea with moderate pellucid marginal degeneration.

Other Tests

Computerized videokeratography is extremely useful in detecting and diagnosing early disease, which may not be readily detectable on slit lamp evaluation. Videokeratography shows low corneal power along the central vertical axis, increased power as the inferior cornea is approached, and high corneal power along the inferior oblique meridians. The videokeratographic pattern has a classic butterfly (or crab-claw) appearance, as shown in the image below.

Corneal topography of early (right eye) and modera Corneal topography of early (right eye) and moderate (left eye) pellucid marginal degeneration.

The most common topographic patterns are the "crab-claw" pattern, present in 61.7%-75% of patients, followed by inferior steepening, seen in 18%-22.2% of patients.[6, 11]

Representative photographs of corneal topography. Representative photographs of corneal topography. Courtesy of the Japanese Journal of Ophthalmology, published by the Japanese Ophthalmological Society.

Pachymetry may reveal a thinning of the inferior cornea. This is a reversal of the typical pattern in which the cornea thickens from the center to the periphery. If any part of the peripheral cornea is thinner than the center, this is a cause for concern.

Orbscan may reveal a typical "kissing birds" appearance.[12]

Histologic Findings

Histologic examination shows an area of thinning that is epithelialized, clear, and avascular. The stroma is thinned, and the Bowman layer may have breaks or may be completely absent in the affected area. Typically, lipid deposits are absent, and a normal-appearing endothelium and the Descemet membrane are present. In acute hydrops, breaks in the Descemet membrane with swelling of the stroma and inflammatory cell infiltrate may be seen.

 

Treatment

Medical Care

Spectacle correction usually fails early in the course of pellucid marginal degeneration (PMD), as the degree of irregular astigmatism increases. In early-to-moderate cases, contact lenses are beneficial in providing visual rehabilitation.

Spectacles and toric hydrophilic contact lenses are useful in mild pellucid marginal degeneration.

Spherical hydrophilic contact lenses cannot correct the astigmatism associated with this condition.

Hybrid contact lenses, which are easier than other lenses to fit to the ectatic cornea, may provide good vision for some patients; however, their poor oxygen permeability often leads to corneal neovascularization, which may adversely affect the prognosis for future corneal transplantation.

Rigid gas-permeable contact lenses provide excellent oxygen transmission to the cornea but are harder than the other lenses to fit. Problems in fitting result from the flattening of the superior cornea and the high degree of against-the-rule astigmatism that often causes the lens to dislocate inferiorly. The upper eyelid may support large-diameter rigid lenses with a high edge lift, but they often cause marked irritation and move excessively with movements of the eyelids, causing the patient's vision to periodically blur. Rigid gas-permeable contact lenses may improve the vision of patients with pellucid marginal degeneration, as in those with keratoconus. However, evidence that these lenses have any effect on the progression of the disease is lacking.

Scleral rigid contact lenses or "mini scleral" contact lenses made from gas-permeable materials are an excellent alternative if fitted by a skilled practitioner.[13, 14]

Surgical Care

In patients who cannot tolerate contact lenses or in those who do not achieve adequate visual acuity with rigid contact lenses because of the degree of ectasia, surgery may be considered.

A number of surgical procedures have been performed to provide visual rehabilitation. Standard-sized penetrating keratoplasty may produce poor results because the inferior edge of the transplant has to be sutured to an abnormally thin cornea, causing a high degree of postkeratoplasty astigmatism in the short- and long-term period. Continued thinning of the host cornea in the inferior aspect produces a situation similar to the situation that indicated surgery.

Large-diameter grafts have been tried to remove as much of the affected cornea as possible, with good success. However, because of the proximity to the limbus and its blood vessels, these grafts may be prone to rejection. Regular-sized grafts that are deliberately decentered in the inferior aspect also work poorly. The degree of astigmatism is large because of the decentering, and the incidence of rejection is high because of the proximity to the limbus. Thermokeratoplasty and epikeratophakia are of only historical interest because the results obtained with these techniques are extremely poor.

Excision of a crescentic wedge of corneal tissue from the inferior cornea, followed by tight suturing, has been reported to reduce the corneal ectasia.[7]  The procedure is usually well tolerated; however, the effect is typically short lived, and thinning and ectasia recur. In addition, this procedure may be hazardous in inexperienced hands. Several instances of wound dehiscence and resultant flat anterior chambers with its attendant problems have been reported with attempts of this procedure. Crescentic lamellar keratoplasty, in which a crescentic transplant is performed to reinforce the area of thinning, has been described, but it may result in a high degree of astigmatism that necessitates subsequent central penetrating keratoplasty.

Modified intrastromal lamellar sclerokeratoplasty incorporating a scleral tunnel and perioperative optical coherence tomography (OCT) mapping is a novel technique developed to correct both corneal thinning and induced corneal astigmatism. Corneal thinning is mapped using OCT. Then, through a scleral tunnel, an intrastromal pocket is created via stromal lamellar dissection under OCT guidance. A 300-μm-thick stromal lamellar graft was inserted in the pocket before closure of the sclera to increase vertical median keratometry.[15]

Currently, the combination of peripheral lamellar crescentic keratoplasty, followed by a central penetrating keratoplasty after a few months is a favored surgical treatment. The lamellar transplant restores normal thickness to the inferior cornea and enables good edge-to-edge apposition at the time of penetrating keratoplasty, reducing the possibility of high postkeratoplasty astigmatism. Furthermore, the central graft that is now sutured to normal-thickness host tissue can be treated with videokeratography-guided selective removal of sutures and astigmatic keratotomy in the usual way to reduce any residual astigmatism.

Ophthalmologists have begun performing the 2 operations in the same sitting, with encouraging results, though this approach is technically difficult. Performing 2 keratoplasty procedures at different times necessitates the use of 2 separate corneas. By performing the 2 procedures in the same sitting, tissue from the same donor may be used, potentially reducing the antigenic load. Because a central graft almost always is needed, performing both procedures at the same time significantly decreases the time needed to attain best-corrected acuity; this is shown in the image below. This consideration is important, as patients are often young and in the active and working phase of their lives.

Image shows simultaneous central penetrating kerat Image shows simultaneous central penetrating keratoplasty and inferior peripheral lamellar keratoplasty performed to treat pellucid marginal degeneration.

The femtosecond laser has also been used to make lamellar dissections to place Intacs and Intracorneal ring segments.[16, 17]

Corneal collagen cross linkage (CXL) also may be of benefit in preventing progression. A 2016 study showed an improvement in visual acuity and reduction of K1 and K2 parameters after CXL.[18]

A case of successful sliding keratoplasty combined with I-CXL was reported in 2016 and was shown to be safe and effective in the treatment of advanced PMD.[19]

Long-term follow-up is required to assess the efficacy of these newer procedures.

Consultations

Treatment of pellucid marginal degeneration with either contact lenses or surgery requires considerable experience. A cornea specialist should be consulted to ensure the best visual outcome.

 

Follow-up

Further Outpatient Care

Patients with pellucid marginal degeneration should receive follow-up care as needed.

Complications

Corneal hydrops similar to that seen in keratoconus, with disruption of the endothelial basement membrane and hydration of the adjacent corneal stroma, rarely occurs in pellucid marginal degeneration (PMD).[20]

Spontaneous corneal perforations in cases of pellucid marginal degeneration are rare. A few case reports have been published in the literature.[20, 21, 22]

Prognosis

No large-scale longitudinal studies of pellucid marginal degeneration have been reported. Quantifying the proportion of patients who eventually require surgery is difficult. Contact lens fitting and surgical correction are more difficult with pellucid marginal degeneration than with keratoconus.

In a follow-up of their ongoing longitudinal study of keratoconus, Rabinowitz and Rasheed have observed 31 patients with pellucid marginal degeneration up to 8 years.[23]  Five patients have required corneal transplantation in 1 eye, and one patient has required transplantation in both eyes. The data must be interpreted with caution because these observations may have been affected by selection bias.