EPITHELIAL BASEMENT MEMBRANE DYSTROPHY

Signs and Symptoms

Epithelial basement membrane dystrophy (EBMD), also known as anterior basement membrane dystrophy and Cogan’s microcystic dystrophy, is one of the more commonly encountered corneal dystrophies in clinical practice.1 Typically, it develops in adults between the ages of 20 and 40 years.2 While EBMD is a bilateral disorder, some patients may show marked asymmetry.

EBMD is often described as map-dot-fingerprint dystrophy because of its classic biomicroscopic signs; these include “maps” (amorphous, grayish-white geographic areas, often containing oval lacunae), “dots” (focal, grayish-white, round or comma-shaped opacities) and “fingerprints” (clusters of irregular concentric lines) within the cornea. The instillation of sodium fluorescein dye helps to delineate these areas, showing negative staining in association with the tissue elevation created by the “maps and dots.” Fingerprint lesions are best identified using retroillumination.

Patients with EBMD are often asymptomatic, with the condition being diagnosed upon routine ocular examination. Occasionally, individuals may display visual symptoms, including blurred vision, fluctuating vision, “ghosting” (i.e., monocular diplopia) or glare. Patients may complain of intermittent blurring or the clinician may note an unstable endpoint on attempted refraction. Less commonly, patients with EBMD report ocular discomfort, such as photophobia or a foreign body sensation. Advanced cases may be predisposed toward the development of recurrent corneal erosion (morning syndrome); in such instances, patients may relate a periodic history of awakening with profound eye pain, blurred vision, blepharospasm or tearing.1-5

Pathophysiology

Corneal dystrophies are noninfectious, non-inflammatory tissue abnormalities related to faulty metabolism or malnutrition. Typically, dystrophies are inherited, bilateral and progressive; however, EBMD deviates somewhat from this rule. Quite often there is no familial history of the disease, and it is not so much progressive as it is chronic, with exacerbations and remissions. In fact, some authorities have classified EBMD not as a dystrophy but rather as a form of corneal degeneration.6

In normal individuals, columnar basal cells represent the foundation of the corneal epithelium. These cells give rise to the corneal basement membrane, which adheres (via hemidesmosomal junctions) to Bowman’s layer, just anterior to the corneal stroma. Individuals with EBMD manifest a dysfunctional basement membrane, which becomes hypertrophied and misdirected.2 The basal cells in these patients manufacture aberrant projections that protrude from an abnormally thickened basement membrane into the superficial epithelium, resulting in the classic clinical findings. The “maps” represent geographic areas of multilaminar basement membrane; the “dots” are intraepithelial microcystic inclusions of cells and cellular debris; “fingerprints” are irregular, fibrogranular ridges of thickened basement membrane that extend into the epithelial layer.1,2

In addition to inducing visible changes in the cornea, the structural alterations associated with EBMD can result in impaired adherence of the overlying epithelium, prompting focal, intermittent “sloughing” of epithelial sheets.3,5 This enables the recurrent corneal erosion syndrome, which is often associated with advanced basement membrane disease.

Management

EBMD does not generally require significant intervention. For asymptomatic patients, periodic evaluation of the corneal changes is usually sufficient. This may be done in a variety of ways, but the use of slit-lamp photography and/or corneal topography helps to provide objective documentation. In vivo confocal microscopy has also been shown to elucidate these anatomical alterations quite effectively, although the availability and cost of such instrumentation makes it impractical for the majority of practicing clinicians.1,2,7

Most patients’ symptoms related to EBMD are similar to dry eye complaints. Ocular lubricants may help alleviate intermittent visual disturbances or discomfort. More substantial disease may warrant the use of hypertonic agents (e.g. 5% sodium chloride solution QID and ointment HS), as these help to deturgesce the epithelium and enhance the cellular adhesion between the epithelial cells and underlying stroma.3,8 An alternative to hypertonic solutions is FreshKote (Focus Laboratories), an ocular lubricant that does not contain sodium chloride, but rather large molecular weight colloidal particles that impart a high oncotic pressure. Hence, this agent may work in a similar capacity to hypertonic salt solutions, but with better overall lubricity and without the associated stinging upon instillation.

Contact lenses also have a role in the management of EBMD: an attempt to “resurface” the irregular epithelium and overcome visual disturbances that sometimes accompany this condition.3 Both hydrogel and rigid lenses may be used in this capacity; however, it is important to select a material with a high Dk/L to minimize corneal edema. Patients with visual symptoms may also be treated via prophylactic epithelial debridement. A study involving 74 eyes of 55 patients treated over 15 years showed that simple manual debridement helped to improve visual acuity by at least one line of Snellen acuity and diminish the incidence of recurrences.9

For those patients who suffer corneal erosions, acute care involves removal of the loose epithelium, topical cycloplegia (e.g., scopolamine 0.25% BID-TID), prophylactic topical antibiotics (e.g., moxifloxacin 0.5% or besifloxacin 0.6% TID) and oral or topical nonsteroidal anti-inflammatory agents as needed for pain. Bandage contact lenses are often helpful in facilitating reepithelialization.8,10,11

Following resolution of the erosion, particular care must be taken to protect the eye while sleeping, to prevent recurrences. Ointments, both bland and hypertonic, are beneficial in preventing abrupt detachment of the epithelium upon awakening.3,12,13 Likewise, sleep masks (or goggles) help prevent unconscious ocular trauma that could otherwise initiate a spontaneous erosion. Nocturnal bandaging is also an accepted modality.

Those individuals who do not respond to conservative management strategies may require more intensive therapy. Noninvasive treatment may involve the use of pharmaceutical agents that mitigate the effects of matrix metalloproteinase. The combination of oral doxycycline and topical corticosteroid drops has been effective in reducing symptoms associated with recurrent erosion.14,15 In one series, treatment with doxycycline 50mg BID and topical fluorometholone 0.1% TID for at least four weeks completed eliminated symptoms in 71% of patients.14

Anterior stromal puncture is a common technique used to manage recurrent corneal erosions. It is designed to initiate scar formation at the level of the basement membrane, which in theory facilitates better adhesion between the epithelium and corneal stroma.13,16 Using a 25-gauge needle under topical anesthesia, the physician places 0.1mm deep perforations, breaching Bowmans’s membrane at 0.25mm intervals, within the area of concern. This technique can also be achieved using the Nd:Yag laser.17 Other surgical options include superficial keratectomy using a diamond burr or excimer laser phototherapeutic keratectomy (PTK).18-21 These two techniques appear to have equivalent efficacy, although diamond burr treatment reportedly has less tendency to induce secondary corneal haze and recurrence.22

Clinical Pearls

Many patients with EBMD present with vague, dry eye-type complaints. Establishing the timing of their symptoms can help to ascertain the true underlying etiology. Those individuals with true aqueous-deficient dry eye typically complain of discomfort and increasing symptoms toward the end of the day, as the tear film becomes more stressed. In contradistinction, patients with EBMD usually report maximum symptomatology in the morning. This is reflective of microcystic and intraepithelial edema, which tends to increase while the eyes are closed.

Patients who describe dry eye-type symptoms that are predominant upon awakening and improve throughout the day should be examined closely for EBMD.

The biomicroscopic signs of EBMD can be exceedingly subtle. In order to best observe the corneal changes, we recommend viewing the ocular surface both with and without fluorescein dye. Also, the cornea should be inspected with retroillumination through a dilated pupil.

A number of older reports suggest that EBMD is a hereditary condition with an autosomal dominant inheritance pattern.23 While many cases are sporadic, it may still be beneficial to suggest comprehensive examinations for all first-order family members of any EBMD patient.

1. Labbe A, Nicola RD, Dupas B, et al. Epithelial basement membrane dystrophy: evaluation with the HRT II Rostock Cornea Module. Ophthalmology 2006; 113(8):1301-8.

2. Kobayashi A, Yokogawa H, Sugiyama K. In vivo laser confocal microscopy findings in patients with map-dot-fingerprint (epithelial basement membrane) dystrophy. Clin Ophthalmol. 2012;6:1187-90.

3. Laibson PR. Recurrent corneal erosions and epithelial basement membrane dystrophy. Eye Contact Lens. 2010;36(5):315-7.

4. Itty S, Hamilton SS, Baratz KH, et al. Outcomes of epithelial debridement for anterior basement membrane dystrophy. Am J Ophthalmol. 2007;144(2):217-221.

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8. Watson SL, Lee MH, Barker NH. Interventions for recurrent corneal erosions. Cochrane Database Syst Rev. 2012;9:CD001861.

9. Itty S, Hamilton SS, Baratz KH, et al. Outcomes of epithelial debridement for anterior basement membrane dystrophy. Am J Ophthalmol. 2007;144(2):217-21.

10. Fraunfelder FW, Cabezas M. Treatment of recurrent corneal erosion by extended-wear bandage contact lens. Cornea. 2011;30(2):164-6.

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14. Wang L, Tsang H, Coroneo M. Treatment of recurrent corneal erosion syndrome using the combination of oral doxycycline and topical corticosteroid. Clin Experiment Ophthalmol. 2008;36(1):8-12.

15. Dursun D, Kim MC, Solomon A, Pflugfelder SC. Treatment of recalcitrant recurrent corneal erosions with inhibitors of matrix metalloproteinase-9, doxycycline and corticosteroids. Am J Ophthalmol. 2001;132(1):8-13.

16. Malecha MA. Anterior stromal puncture for recurrent corneal erosion after laser in situ keratomileusis. J Cataract Refract Surg. 2004;30(2):496-8.

17. Tsai TY, Tsai TH, Hu FR, Hou YC. Recurrent corneal erosions treated with anterior stromal puncture by neodymium: yttrium-aluminum-garnet laser. Ophthalmology. 2009;116(7):1296-300.

18. Tzelikis PF, Rapuano CJ, Hammersmith KM, et al. Diamond burr treatment of poor vision from anterior basement membrane dystrophy. Am J Ophthalmol 2005; 140(2):308-10.

19. Ryan G, Lee GA, Maccheron L. Epithelial debridement with diamond burr superficial keratectomy for the treatment of recurrent corneal erosion. Clin Experiment Ophthalmol. 2012 Dec 10. doi: 10.1111/ceo.12052. [Epub ahead of print]

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22. Sridhar MS, Rapuano CJ, Cosar CB, et al. Phototherapeutic keratectomy versus diamond burr polishing of Bowman’s membrane in the treatment of recurrent corneal erosions associated with anterior basement membrane dystrophy. Ophthalmology 2002; 109(4):674-9.

23. Waring GO 3rd, Rodrigues MM, Laibson PR. Corneal dystrophies. I. Dystrophies of the epithelium, Bowman’s layer and stroma. Surv Ophthalmol. 1978; 23(2):71-122.