Review of Cornea & Contact lenses

With Amniotic Membranes

This collagen-rich tissue is emerging as a new method for managing EBMD and recurrent corneal erosion. How does it perform clinically?

By Richard B. Mangan, OD

Release Date: October 2014
Expiration Date: October 1, 2017

Goal Statement:

This course reviews the relationship between epithelial basement membrane dystrophy (EBMD) and recurrent corneal erosion (RCE), and discusses the use of sutureless amniotic membrane for visual distortion related to RCE in EBMD.

Faculty/Editorial Board:

Dr. Richard B. Mangan, OD Dr. Richard B. Mangan, OD, is a consultative optometrist at Bennett & Bloom Eye Centers in Louisville, KY.

Credit Statement:

This course is COPE approved for 1 hour of CE credit. COPE ID 43324-AS. Check with your local state licensing board to see if this counts toward your CE requirements for relicensure.

Joint-Sponsorship Statement:

This continuing education course is joint-sponsored by the Pennsylvania College of Optometry.

Disclosure Statement:

Dr. Mangan has no financial disclores relevant to this course.

Epithelial basement membrane dystrophy (EBMD) also known as map-dot-fingerprint dystrophy or Cogan’s microcystic dystrophy, is a bilateral anterior corneal degeneration characterized by grayish map-like lines, possibly accompanied by microcysts, within a thickened corneal epithelium. Unlike most dystrophies that typically show clear deterioration or progression, clinical findings associated with EBMD are often variable. It is not uncommon for EBMD to be discovered during anterior segment surgery, as the diseased epithelium can become loose, irregular or even erode. Patients who complain of fluctuating or blurry vision may be experiencing the effects of EBMD, as it predisposes patients to recurrent corneal erosion (RCE), which is known to impact vision.

RCE is a relatively common disorder in which a segment of the outer epithelial layer of the cornea tears or becomes loose, often resulting in severe pain and secondary tearing, epiphora, rhinorrhea, redness and photophobia. These symptoms are most often present during sleep or upon awakening, and are usually linked to previous trauma (i.e., corneal abrasion), corneal dystrophy (i.e., EBMD, lattice, granular, Reis-Buckler) or a combination of both. Patients presenting with RCE will report a history of abrasion or trauma roughly 65% of the time.1 Comparatively, epithelial basement membrane dystrophy is by far the most common corneal dystrophy and is associated with RCE approximately one-third of the time.2 However, RCE may also occur spontaneously without any identifiable risk factors.3

Over the years, a number of treatment modalities have been proposed and used clinically to manage EBMD and/or recurrent corneal erosions: antibiotic drops and ointments, lubricants, topical steroids, hypertonic drops/ointments, autologous serum, bandage contact lenses, punctal plugs, platelet- or albumin-rich tears, oral doxycycline and vitamin C supplements. Additionally, surgical options such as debridement, anterior stromal puncture, burr or brush therapeutic keratectomy (BTK) and photothera-peutic keratectomy (PTK) can also be used if noninvasive methods are ineffective.

An increasing amount of anecdotal evidence released in recent years, however, supports the use of amniotic membrane tissue as a new treatment method for RCE.


The corneal epithelium—like the cornea itself—is multilayered: the column-shaped basal cells that make up the deepest layer are covered by several layers of polyhedral-shaped wing cells and three to four superficial layers of flattened squamous cells. Each of these layers is continually undergoing mitosis, with basal and wing cells migrating anteriorly as squamous cells slough off in the tear film. Additionally, the basal epithelium also produces and adheres to its underlying basement membrane using an adhesion complex made up of hemidesmosomes and type VII collagen-anchoring fibrils.4

Sometimes, due to trauma, dystrophy or both, an abnormal deposition of the epithelial basement membrane can disrupt this adhesion complex.4 Believed to be the main contributing factor to RCE, this results in a thicker, multilaminar membrane that is usually misdirected into the epithelium, causing irregularity and vision degradation.5

Inflammation has also been implicated as a key contributor to recurrent corneal erosion syndrome.6 RCE patients tend to show increased levels of polymorphonuclear neutrophils (PMNs) between cells and at the basement membrane interface.7 Also, increased levels of matrix metalloproteinases (both MMP-2 and MMP-9) in epithelial cells and the tear film have been reported.8 MMPs break down the extracellular matrix (laminin and type IV and VII collagen) of the basement membrane and adjacent tissue for remodeling purposes.

Fortuitously, amniotic tissue is also largely made up of the same extracellular components (type IV and VII collagen, laminin and fibronectin) that partially comprise the cornea.9 Amniotic tissue also contains hyaluronic acid, which has direct and indirect (T-cell suppression) anti-inflammatory properties.10 It is believed that these anatomical and physiological characteristics are responsible for the wound healing properties of amniotic membrane tissue.11 This tissue exhibits antimicrobial properties and is said to promote epithelialization, suppress inflammation and inhibit scarring, without the potentially harmful side effects associated with topical and oral medications.12


Sutureless amniotic membranes are either cryopreserved (Prokera) or dehydrated (AmbioDisk or BioD Optyx) when processed and packaged.

Prokera (Bio-Tissue) is a class II medical device comprised of a cryopreserved amniotic membrane graft fastened to a plastic ring set; it must be kept or stored in the freezer. Its inner diameter is 16mm. The related Prokera Slim offers a thinner outer ring segment, yield ing an inner overall diameter of 17.9mm, while the Prokera Plus is thicker (200µm) and recommended for more severe corneal compromise that would require more aggressive healing response.

AmbioDisk (IOP Ophthalmics) and BioD Optyx (BioD), on the other hand, are typically stored in a controlled room environment, but can be refrigerated. After the dehydrated amniotic membrane is placed on the eye, a soft bandage contact lens is used to secure its placement. IOP Ophthalmics offers the Ambio 2 (35µm thick) and the Ambio 5 (100µm), both with a diameter of 15mm. BioD Optyx comes in two disc sizes (12mm and 15mm) with a central thickness of 40 to 60 microns.

Aside from EBMD and RCE, sutureless amniotic membrane transplantation has also been found to be useful in the management of a wide array of other corneal, conjunctival and ocular surface conditions, including: acute Stevens- Johnson syndrome/TEN, acute burns, neurotrophic defects or persistent corneal epithelial defects, filamentary keratitis, microbial keratitis, VKC, bullous keratopathy, Salzmann’s nodular degeneration, dry eye syndrome or recalcitrant SPK, oculoplastic procedures, and non-healing epithelial defects after PRK/PTK.13-18

Amniotic membrane grafts are also sometimes used in conjunction with ophthalmic surgical procedures, such as: SPK, corneal perforation, high-risk corneal transplantation, pterygium removal, band keratopathy, scleral melts, limbal graft for partial or total stem cell deficiency, conjunctivochalasis or conjunctival reconstruction, and glaucoma surgery.18-20


A 63-year-old Caucasian male presented with the primary complaint of blurry and distorted vision in his right eye. He reported symptoms started soon after he underwent cataract surgery and indicated that, visually, it was comparable to looking through cellophane. He was referred in for a surgical consult for clinically significant EBMD after medical therapy (Refresh artificial tears and Muro 128 ung QHS) had proven ineffective.

Best corrected entrance acuities were 20/60-2 (PH 20/30+2) and 20/25 (PHNI), respectively, and he exhibited diffuse map-dot-fingerprint changes to the epithelium OD >> OS (Figures 1 and 2), which was visible on slit-lamp examination. Oculus corneal topographical analysis confirmed surface irregularity consistent with EBMD (Figure 3), while wavefront aberrometry revealed clinically significant higher-order aberrations with a root mean square (RMS) value of 0.9 (for reference, normal is 0.3 or less).

Fig. 1. Right eye—clinically
significant EBMD (20/60 BCVA).Fig. 2. Left Eye—Mild EBMD
(20/25 BCVA).
Fig. 3. Abnormal topography OD

After discussing the pathogenesis of recurrent corneal erosion syndrome and the risks, benefits and surgical alternatives, a joint decision was made to move forward with debridement and amniotic membrane transplant using Prokera.

Once the eye was appropriately anesthetized using Tetravisc, the corneal epithelium was gently debrided, leaving a residual 8mm epithelial defect. Preservative-free artificial tears and antibiotic drops were instilled prior to insertion of the amniotic membrane. Once the ring was removed from its sterile packaging, the amniotic tissue was irrigated using sterile saline and then placed on the right eye uneventfully. Slit-lamp examination confirmed adequate centration with normal lid tautness. Transpore tape was applied to the superior lid to aide in ring retention.

The patient was prescribed Polytrim antibiotic drops QID OD and hydrocodone 10/500mg. Before discharge, he was instructed to call our office should he experience any significant pain or discomfort. Additionally, he was told to avoid underwater activity or the operation of motor vehicles or other heavy equipment, as he can expect his vision to be blurry and depth perception to be temporarily compromised while the membrane is in place.

The patient returned for his scheduled follow-up one week following debridement and Prokera application. He reported there was significant discomfort during the first night, but that the pain resolved by the second day. He also reported intermittent foreign body sensation and tearing with epiphora since his treatment. His entrance acuity was 20/300 (PH 20/80).

The Prokera ring segment was removed uneventfully at the slit-lamp and the cornea showed complete reepithelialization with only trace haze. Vision was reassessed after ring removal and lubrication. It measured 20/80 (PH 20/30-2). The patient was started on Lotemax gel QID OD and Muro 128 QHS OD, and his Polytrim antibiotic drops were discontinued. His next follow-up was scheduled for one week later.

At his two-week follow-up appointment, his vision had improved to 20/30+ acuity; by one month, he refracted at 20/20- OD. He reported no residual glare or foreign body sensation, and slit-lamp examination confirmed a smooth epithelium and no residual stromal haze. Topical steroids were discontinued and he was asked to continue his Muro 128 ointment at bedtime until he returns for another follow-up with his family optometrist in six months.


It is important to note that most patients experience some discomfort the night following the procedure and into the next morning. This is mostly due to the large epithelial defect created from the debridement rather than the placement of the amniotic membrane. Patients are instructed to call our office if the discomfort continues for greater than 24 hours, as this may be related to a decentered ring segment. It is also reasonable to proactively schedule the patient for a one-day postoperative visit if there is any concern about delayed decentration after ring has been applied.

In most cases, after centration has been confirmed at the slit-lamp, we apply Transpore tape across the breadth of the upper eyelid, bordering the lid crease. This keeps the interpalpebral fissure width small, decreasing the risk of ring decentration or escape. Because the lids are not taped completely shut, patients are still able to deliver topical antibiotics and lubricants uneventfully throughout the day.

The ring segment often causes foreign body sensation; if a patient returns complaining of significant discomfort, it is important to look for decentration of the ring. Sodium fluorescein dye can be instilled to evaluate not only the epithelial defect, but the integrity of the amniotic tissue. If centration seems to be the issue, repositioning and partial tarsorrhaphy are sometimes warranted to improve stability.


Conventional medical therapy for recurrent corneal erosion syndrome is associated with a high recurrence rate.21-23 While surgical intervention is more effective for refractory cases, demonstrating an 85% or higher initial treatment success rate (Table 1), there may be a greater risk of scarring over the visual axis or an unwanted change in refractive error with surgery.24,25

Table 1. Initial Treatment Success Rates Reported For RCE
Authors Treatment Technique # of Eyes Success Rate
Buxton & Fox Debridement   13 85%
McClean et al. Anterior Stromal Puncture 20-gauge needle 21 86%
Tsai et al. Anterior Stromal Puncture Nd:Yag 33 85%
Buxton & Constad Superficial Keratectomy Diamond Burr 33 97%
Soong et al. Superficial Keratectomy Diamond Burr 54 94%
Hodkin & Jackson Superficial Keratectomy Amoils Brush 23 88%
Maini & Loughnan Phototherapeutic Keratectomy Excimer Laser 76 89%

Research performed at the Ocular Surface Center in Florida suggests a comparable success rate when the Prokera ring is used in conjunction with debridement. In a small study, Huang, Sheha and Tseng studied the effects of debridement and Prokera placement for RCE in 11 eyes by a single surgeon. Ten of the 11 eyes were symptom-free during the mean follow-up period of 13.7 +/- 2.2 months, with reepithelialization occurring between days four through seven.26

In our experience, epithelial debridement with Prokera has been a reasonable approach to managing visual symptoms secondary to EBMD/RCE syndrome. Prokera may be stored in-office, making it readily available for either planned or untimely ocular urgencies. Its documented wound healing properties warrant its consideration for nonsurgical intervention when conventional medical therapy has not met expectations for you or your patient.

The author wishes to acknowledge the contribution of Gary Wörtz, MD, who provided the case report data.


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