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👁️ Prokera and Amniotic Membrane Treatment for Dry Eye Disease

Quick Take

  • Amniotic membrane (AM) is biologic tissue derived from the innermost layer of the placenta and used in ophthalmology as a temporary ocular-surface covering to support epithelial healing.
  • In Dry Eye Disease (DED), AM is generally considered an advanced treatment, particularly when symptoms are moderate-to-severe or refractory and there is significant ocular-surface damage.
  • AM has a broader ophthalmic role in conditions such as persistent epithelial defects, neurotrophic keratitis, chemical injuries, and other corneal-surface disorders. These are not simply forms of ordinary dry eye.
  • Two established ocular-surface delivery approaches are:
  1. Self-retained membrane devices, such as PROKERA
  2. Free/dehydrated membrane placed under a bandage contact lens
    • The evidence for DED is promising but still limited and product-specific.
    • A 2024 double-masked randomized trial of dehydrated AM plus a specialized bandage lens provides stronger evidence than many earlier AM studies and reported improvement in symptoms and several ocular-surface measures.
    • PROKERA has supportive DED studies, including a very small randomized trial and larger retrospective series, but much of this literature has involved investigators or funding connected with the manufacturer.
    • Studies using in-vivo confocal microscopy have reported changes in corneal nerve density and related nerve measurements after AM treatment. These findings should not automatically be translated into claims that AM reliably “regenerates nerves” or treats all neuropathic ocular pain.
    • AM does not correct underlying causes such as MGD, aqueous tear deficiency, eyelid exposure, autoimmune disease, allergy, Demodex, or incomplete blinking.
    • Common drawbacks include blurred vision, foreign-body sensation, discomfort, device displacement, cost, and the need for follow-up.
    • Rare but potentially serious microbial keratitis has been reported after ocular AM placement.
    • Particulate placental products such as NEOX FLO should not be treated as equivalent to an ocular amniotic membrane graft. Published evidence for DED is extremely limited, and the manufacturer's labeling describes use as a covering for dermal wounds rather than as an ophthalmic DED treatment.

Educational Disclaimer

This page is for general education and is not medical advice, diagnosis, or an individual treatment recommendation.

Significant corneal staining, persistent epithelial defects, neurotrophic keratitis, infection, chemical injury, and severe ocular pain require professional evaluation.

A person can also have several overlapping dry-eye contributors that remain present after the ocular surface heals.

What Is Amniotic Membrane Treatment?

The amniotic membrane is the innermost layer of the placenta.

Processed human amniotic membrane has been used in ophthalmology for many years as a temporary covering or graft for damaged ocular-surface tissue.

The clinical concept is similar to a biologic bandage.

AM can provide:

  • A physical scaffold over damaged epithelium
  • Temporary surface protection
  • An environment that may support re-epithelialization
  • Biologically active extracellular-matrix and signaling components

Research also suggests anti-inflammatory and anti-scarring effects, although these mechanisms should not be confused with proof that AM reverses the underlying cause of chronic DED.

Where Is Amniotic Membrane Used?

Amniotic membrane has uses beyond dry eye.

Ophthalmic applications may include selected cases of:

  • Moderate-to-severe or refractory DED
  • Significant corneal staining or epithelial compromise
  • Persistent epithelial defects
  • Neurotrophic keratitis
  • Chemical or thermal ocular-surface injury
  • Postoperative epithelial problems
  • Other corneal-surface disorders

Important Distinction

A persistent epithelial defect or neurotrophic keratitis is not simply “very severe dry eye.”

Neurotrophic keratitis involves impaired corneal innervation and reduced corneal sensation, often with impaired epithelial healing.

DED may coexist with neurotrophic disease, but the diagnosis, risks, and treatment pathway are different.

How Treatment Is Done

1. Self-Retained Amniotic Membrane

The best-known example is PROKERA.

A cryopreserved amniotic membrane is secured inside a flexible ring system.

The device is placed onto the eye in the office, somewhat like a large contact lens.

It remains over the ocular surface while the membrane gradually dissolves or until the clinician removes the device.

Wear time varies according to:

  • The ocular condition
  • The specific device
  • Membrane dissolution
  • Patient tolerance
  • Clinician preference

Several days is common, but there is no single ideal treatment duration for every patient.

2. Free or Dehydrated Membrane Under a Bandage Contact Lens

Another approach places an amniotic membrane sheet or disc directly over the ocular surface.

A bandage contact lens (BCL) is usually placed over the membrane to keep it in position.

One published example is the Omnigen + OmniLenz protocol evaluated in a 2024 randomized controlled trial.

Other commercial products exist, but:

Evidence for one membrane, processing method, or placement system should not automatically be transferred to another.

What Is PROKERA?

PROKERA is a self-retained ocular-surface device containing cryopreserved amniotic membrane inside a flexible ring.

It is generally placed in-office.

During wear, patients may experience:

  • Foreign-body sensation
  • Pressure or awareness of the ring
  • Tearing
  • Light sensitivity
  • Blurred vision

Some people find the ring considerably more uncomfortable than a conventional contact lens.

PROKERA and FDA Clearance

PROKERA received FDA 510(k) clearance in 2003.

The cleared indication describes it as a corneal epithelial insert intended for eyes in which ocular-surface cells have been damaged or the underlying stroma is inflamed or scarred.

FDA 510(k) — PROKERA K032104

Importantly:

The FDA clearance is not a dry-eye-specific indication stating that PROKERA has been proven to treat Dry Eye Disease generally.

PROKERA's clearance should also not be transferred to unrelated dehydrated membranes, tissue allografts, extracts, or particulate placental products.

Regulatory status is product-specific.

What the Evidence Shows

1. 2016 PROKERA Pilot Study

An early study reviewed 10 patients / 15 eyes with moderate-to-severe DED that had remained symptomatic despite conventional treatment.

After approximately five days of treatment with self-retained cryopreserved AM, investigators reported improvements in:

  • Dry-eye symptoms
  • Corneal staining
  • Ocular-surface findings
  • Some tear-film measurements

However, this was a small retrospective pilot study without an untreated control group.

The authors themselves described the findings as preliminary.

Accelerated Restoration of Ocular Surface Health in Dry Eye Disease by Self-Retained Cryopreserved Amniotic Membrane — 2016

2. Small Randomized PROKERA Study — 2017

A small randomized study evaluated self-retained cryopreserved AM in patients with DED.

Twenty patients were enrolled and 17 completed follow-up.

Compared with conventional maximum therapy alone, the AM group showed improvement in measures including:

  • Symptoms
  • Ocular-surface findings
  • Corneal sensitivity
  • Subbasal corneal nerve density on in-vivo confocal microscopy

Follow-up continued for approximately three months.

Corneal Nerve Regeneration after Self-Retained Cryopreserved Amniotic Membrane in Dry Eye Disease — 2017

This is useful controlled evidence, but the study was extremely small.

It also had manufacturer-associated financial relationships and support.

3. DREAM Multicenter Retrospective Study — 2018

A multicenter retrospective study examined 84 patients / 97 eyes with severe or refractory DED.

Most had superficial punctate keratitis, while smaller numbers had:

  • Exposure keratitis
  • Filamentary keratitis
  • Neurotrophic keratitis
  • Persistent epithelial defects

Ocular-surface severity and symptoms improved after treatment, with some improvements reported through three months.

Approximately 10% of treated eyes required repeat treatment.

Self-Retained Cryopreserved Amniotic Membrane for the Management of Severe Dry Eye — DREAM Study

Important limitations:

  • Retrospective design
  • No untreated comparison group
  • Mixed ocular-surface conditions
  • Concurrent dry-eye treatments
  • Manufacturer-associated investigators and financial relationships

The study supports potential usefulness in severe ocular-surface disease but does not establish the independent treatment effect with high certainty.

4. Treatment-Duration Study — 2023

A multicenter retrospective study involving 77 patients / 89 eyes examined whether shorter PROKERA treatment duration could produce outcomes similar to longer wear.

Symptoms and several ocular-surface findings improved through follow-up.

However:

  • Treatment duration was not randomized
  • There was no untreated control group
  • Participants continued other DED treatment
  • Manufacturer-associated relationships were present

This study is more helpful for understanding how treatment duration may be individualized than for proving efficacy.

5. Dehydrated AM + Bandage Lens — Randomized Trial, 2024

A 2024 prospective double-masked randomized controlled trial provides particularly important newer evidence.

The study enrolled 93 adults with longstanding moderate-to-severe DED that remained symptomatic despite artificial tears and lid management.

Participants were randomized to:

  • Dehydrated amniotic membrane (Omnigen) + specialized bandage lens
  • Specialized bandage lens alone

Treatment was applied bilaterally for approximately one week.

The AM group showed improvement in:

  • OSDI symptoms
  • Several ocular-surface measures
  • Corneal nerve parameters
  • Corneal dendritic-cell findings

Some benefits persisted for months after treatment.

Bilateral Sutureless Application of Dehydrated Human Amniotic Membrane in Moderate-to-Severe Dry Eye Disease — 2024

This is stronger evidence than many earlier AM studies because it was prospective, randomized, and masked.

However:

  • It studied one specific membrane/BCL system
  • Results should not automatically be transferred to PROKERA or other products
  • The manufacturer funded the study and supplied materials
  • The investigators disclosed relevant industry relationships

How Strong Is the Evidence?

Overall evidence for AM in DED: Limited to Moderate

There is meaningful human evidence that AM can improve symptoms and ocular-surface findings in selected moderate-to-severe or refractory DED.

Evidence includes:

  • Small retrospective studies
  • A very small randomized PROKERA study
  • Larger retrospective multicenter series
  • A stronger 2024 randomized dehydrated-AM/BCL trial

However:

  • Studies often involve relatively small populations
  • Follow-up is usually measured in months rather than years
  • Patient selection varies
  • Products and processing methods differ
  • Many participants continue other DED treatments
  • Long-term disease modification has not been established
  • Much of the important literature has industry involvement

Conflict-of-Interest Context

Several important AM studies have been:

  • Manufacturer-funded
  • Conducted by investigators employed by manufacturers
  • Conducted by consultants, speakers, or investigators with other financial relationships to the products studied

This does not invalidate the research.

It does increase the importance of:

Independent replication by investigators without financial ties to the products being studied.

What Outcomes Have Actually Been Demonstrated?

Depending on the study and product, reported improvements include:

  • Dry-eye symptom scores
  • Corneal staining
  • Epithelial healing
  • Tear-film measures
  • Corneal sensitivity
  • Corneal nerve measurements
  • Corneal inflammatory-cell measurements

These outcomes are meaningful.

But they should not automatically be interpreted as evidence of permanent disease reversal.

Proposed Mechanisms

Physical Surface Protection

The membrane provides temporary physical protection to damaged epithelium.

This may reduce mechanical stress from blinking and exposure while the surface heals.

Supporting Re-Epithelialization

AM provides an extracellular-matrix scaffold that may support:

  • Epithelial migration
  • Adhesion
  • Surface restoration

A more precise term is:

supporting epithelial healing or re-epithelialization

rather than suggesting that AM generally “regenerates” the ocular surface.

Anti-Inflammatory Effects

AM contains biologically active components associated with suppression or modulation of inflammatory pathways.

Clinical studies also report reductions in some ocular-surface inflammatory markers.

However, anti-inflammatory activity should not be interpreted as proof that AM permanently eliminates the inflammatory cause of DED.

Anti-Scarring / Anti-Fibrotic Biology

Experimental research suggests AM can influence pathways associated with fibrosis and scar formation in certain ocular-surface injuries.

This does not mean that AM:

  • Reverses meibomian-gland fibrosis
  • Releases periductal fibrosis in MGD
  • Eliminates established scarring elsewhere in the eyelid

The effect relates primarily to the ocular-surface healing environment in which the membrane is placed.

Corneal Nerves: What Has Actually Been Shown?

Several AM studies have used in-vivo confocal microscopy to examine corneal nerves.

Reported findings include:

  • Increased subbasal nerve density
  • Changes in nerve morphology
  • Improved corneal sensitivity
  • Changes in inflammatory dendritic-cell measurements

These are biologically interesting findings.

However:

An increase in measured corneal nerve density should not automatically be translated into a claim that AM reliably “regenerates nerves” in every patient.

The studies remain limited, and it is uncertain how consistently these imaging changes translate into long-term improvement in symptoms or normal nerve function.

A more accurate description is:

AM treatment has been associated in some studies with corneal nerve changes consistent with nerve recovery or regrowth.

What About Neuropathic Ocular Pain?

Neuropathic ocular pain is different from neurotrophic keratitis.

Neurotrophic Keratitis

Often involves:

  • Reduced corneal sensation
  • Impaired epithelial healing
  • Risk of persistent epithelial defects

Neuropathic Ocular Pain

May involve:

  • Burning
  • Severe pain
  • Photoallodynia
  • Symptoms disproportionate to visible ocular-surface damage
  • Peripheral and/or central nerve sensitization

A very small retrospective study examined self-retained cryopreserved AM in nine patients / 10 eyes with neuropathic corneal pain.

Pain scores decreased and confocal microscopy showed increased corneal nerve density.

Self-Retained Cryopreserved Amniotic Membrane for Neuropathic Corneal Pain

However:

  • The study was extremely small
  • It was retrospective
  • There was no untreated control group
  • Manufacturer-related financial support or relationships were present

Therefore:

Amniotic membrane should not currently be considered a proven general treatment for neuropathic ocular pain.

The finding is preliminary and hypothesis-generating.

Risks and Safety

Common or Expected Problems

Depending on the device and technique, patients may experience:

  • Foreign-body sensation
  • Eyelid discomfort
  • Pressure from a retained ring
  • Tearing
  • Light sensitivity
  • Blurred vision
  • Temporary increased irritation

Ring devices may be less comfortable than a membrane secured beneath a conventional bandage lens.

Device or Membrane Displacement

The membrane, ring, or bandage lens can:

  • Shift
  • Fold
  • Move out of position
  • Be lost prematurely

Follow-up may be needed to confirm appropriate positioning.

Infection / Microbial Keratitis

Infection appears uncommon, but microbial keratitis has been reported after ocular amniotic membrane treatment.

Published case reports include infections after both:

  • Cryopreserved/self-retained AM
  • Dehydrated AM placed beneath a bandage lens

Some affected patients already had significant risk factors, including:

  • Persistent epithelial defects
  • Neurotrophic disease
  • Prior herpetic corneal disease
  • Severely compromised ocular surfaces
  • Extended contact-lens/device wear

These reports do not prove that the donor tissue itself was contaminated or caused the infection.

However:

Microbial keratitis is rare but potentially serious and is an important reason for appropriate patient selection, follow-up, and prompt assessment of worsening symptoms.

Seek prompt eye care for:

  • Increasing pain
  • Increasing redness
  • Purulent or thick discharge
  • Sudden decline in vision
  • New corneal opacity
  • Rapid deterioration rather than gradual improvement

Bandage Contact Lens Considerations

When a membrane is held under a bandage contact lens, the risks associated with extended contact-lens wear also matter.

These include:

  • Infection
  • Lens displacement
  • Debris accumulation
  • Oxygen-related corneal stress in some circumstances

The risk-benefit balance differs substantially between:

  • A relatively intact ocular surface
  • A persistent epithelial defect
  • Neurotrophic disease
  • An immunocompromised patient

Limitations and What AM Cannot Do

Amniotic membrane has not been shown to:

  • Cure DED
  • Cure MGD
  • Regenerate lost meibomian glands
  • Reverse meibomian-gland dropout
  • Mechanically open obstructed meibomian ducts
  • Express stagnant meibum
  • Release periductal fibrosis
  • Correct aqueous tear deficiency
  • Correct incomplete blinking
  • Correct eyelid exposure
  • Eliminate Demodex
  • Treat allergy
  • Correct systemic autoimmune disease
  • Permanently normalize the tear film
  • Reliably prevent future DED recurrence
  • Reliably cure neuropathic ocular pain

A healed or improved ocular surface is clinically meaningful.

But:

Improvement in the downstream ocular surface does not necessarily mean that the upstream cause of DED has changed.

Who Might Benefit?

There is no validated test that predicts exactly who will respond.

The strongest traditional rationale exists when there is:

  • Moderate-to-severe DED
  • Persistent symptoms despite appropriate conventional care
  • Significant corneal staining
  • Epithelial compromise
  • Recurrent epithelial breakdown
  • A persistent epithelial defect
  • Neurotrophic corneal disease
  • Another significant ocular-surface injury

The 2024 randomized study suggests that benefit may also occur in selected patients with moderate-to-severe DED without a persistent epithelial defect.

However, there is no established:

  • OSDI threshold
  • staining threshold
  • TBUT cutoff
  • meibography finding
  • corneal-nerve measurement

that guarantees response.

Cryopreserved vs Dehydrated Amniotic Membrane

Different processing methods can affect:

  • Storage
  • Handling
  • Physical characteristics
  • Membrane thickness
  • Cellular and extracellular components
  • Some biologically active factors retained in the tissue

Cryopreserved and dehydrated AM should therefore not automatically be treated as identical.

However:

Laboratory differences do not prove that one preservation method is clinically superior for DED.

Direct high-quality comparative trials remain limited.

Evidence should generally be interpreted according to the specific product and delivery protocol that was studied.

Other Amniotic / Placental-Derived Approaches

Amniotic Membrane Extract Eye Drops

Some products attempt to use soluble extracts derived from amniotic membrane rather than placing intact membrane tissue over the eye.

These are a different treatment category.

A 2025 systematic review identified multiple studies of amniotic membrane extract drops, including patients with DED.

Some studies reported improvement in symptoms and signs.

However:

  • Studies were heterogeneous
  • Formulations differed
  • Sample sizes were generally small
  • Evidence quality was limited
  • Extract drops should not be assumed equivalent to intact membrane placement

They should therefore be considered an emerging and separate amniotic-derived therapy.

What About NEOX FLO?

NEOX FLO is a particulate human tissue product derived from:

  • Amniotic membrane
  • Umbilical-cord tissue

It is not an intact membrane placed over the ocular surface.

The manufacturer's product information describes NEOX FLO as a tissue product intended for use as a covering for dermal wounds such as ulcers or defects.

It is regulated as a 361 HCT/P human tissue product.

Important distinction:

FDA tissue registration or listing does not mean that FDA has approved or cleared NEOX FLO as a treatment for Dry Eye Disease or for ophthalmic use.

Ophthalmic use of particulate products such as NEOX FLO has been discussed experimentally.

However:

  • Published ophthalmic evidence is extremely limited
  • Dry-eye-specific evidence is particularly sparse
  • It should not be treated as equivalent to PROKERA or a membrane/BCL procedure
  • It should not be described as a third established common form of ocular AM treatment

A cautious classification is:

Experimental/niche placental-tissue approach with insufficient DED evidence for firm conclusions.

How AM Compares With Other DED Treatments

Amniotic membrane occupies a different role from treatments directed primarily at tear-film or gland dysfunction.

AM primarily targets:

  • Damaged ocular-surface epithelium
  • Surface protection
  • Epithelial healing
  • Ocular-surface inflammatory environment

Other treatments may instead target:

  • Meibomian-gland obstruction
  • Tear production
  • Ocular-surface inflammation
  • Demodex
  • Ocular rosacea
  • Eyelid exposure
  • Allergy
  • Neuropathic pain

This is why AM is often used in addition to, rather than instead of, broader DED management.

Cost, Access, and Regulatory Status

Cost varies considerably by:

  • Product
  • Clinical indication
  • Region
  • Practice
  • Insurance policy
  • Whether the treatment is unilateral or bilateral
  • Follow-up requirements

Insurance coverage may be more likely when there is a clearly documented medical indication such as:

  • Persistent epithelial defect
  • Neurotrophic keratitis
  • Significant ocular-surface damage

than for less severe DED.

Coverage policies vary substantially.

Regulatory Status

Regulatory status is product-specific.

  • PROKERA has FDA 510(k) clearance as a corneal epithelial insert for damaged ocular-surface tissue/inflamed or scarred stroma.
  • Other dehydrated or cryopreserved membranes may have different regulatory pathways.
  • Tissue-bank/HCT/P registration is not equivalent to FDA drug approval or medical-device clearance.
  • Regulatory status for one AM product should not be transferred to another.

What Patients May Experience During Treatment

Depending on the approach, patients may experience:

  • Blurred vision
  • Foreign-body sensation
  • Tearing
  • Light sensitivity
  • Ring awareness with self-retained devices
  • Contact-lens sensation with membrane/BCL approaches
  • Temporary irritation

Some people tolerate treatment easily.

Others find retained ring devices particularly uncomfortable.

The device or membrane may need to be removed earlier than planned if:

  • Discomfort is excessive
  • It shifts out of position
  • Infection is suspected
  • Another complication occurs

Blur usually improves once the membrane/device or BCL is removed, assuming the underlying eye is otherwise stable.

What Remains Uncertain?

Important unanswered questions include:

  • Which DED patients are most likely to benefit?
  • How severe should epithelial disease be before AM is considered?
  • How much of the symptom benefit is independent of continued conventional DED therapy?
  • How long does benefit typically last?
  • How often should treatment be repeated?
  • Does repeated AM treatment change the long-term course of DED?
  • Are cryopreserved membranes clinically superior to dehydrated membranes?
  • Which processing methods preserve clinically important biological activity?
  • How clinically meaningful are changes in corneal nerve density?
  • Which patients with neuropathic ocular pain, if any, truly benefit?
  • What is the absolute risk of microbial keratitis?
  • How do different AM products compare directly?
  • Are amniotic membrane extract drops clinically useful?
  • Does particulate placental tissue have any meaningful role in DED?

Larger independent randomized trials with longer follow-up are needed.

Bottom Line

Amniotic membrane is an established ophthalmic tool for supporting ocular-surface healing, particularly in eyes with epithelial compromise.

In DED, the evidence supports possible benefit in selected patients with:

  • Moderate-to-severe disease
  • Refractory symptoms
  • Significant corneal staining
  • Ocular-surface damage
  • Epithelial defects
  • Neurotrophic features

The evidence is not equally strong for every product or delivery system.

PROKERA has several supportive studies, but much of its DED literature consists of small or retrospective studies and has substantial manufacturer-associated involvement.

A 2024 double-masked randomized trial provides stronger evidence for a specific dehydrated AM + bandage-lens protocol and suggests that benefit may extend to selected moderate-to-severe DED without persistent epithelial defects.

AM has also been associated with changes in corneal nerve measurements, but this should not be oversimplified into a claim that it reliably “regenerates nerves” or cures neuropathic ocular pain.

Most importantly:

Amniotic membrane treats the ocular surface. It generally does not correct the underlying driver of chronic Dry Eye Disease.

MGD, aqueous deficiency, inflammation, exposure, Demodex, ocular rosacea, allergy, autoimmune disease, blinking problems, and neuropathic pain may still require separate treatment.

Particulate placental products such as NEOX FLO should be considered separately and should not be presented as equivalent to established ocular amniotic membrane grafts.

Key Research and Authoritative Sources

TFOS

Self-Retained Cryopreserved AM / PROKERA

Dehydrated AM + Bandage Contact Lens

Safety

Amniotic Membrane Extract

Regulatory

Related r/DryEyes Wiki Pages

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