This case-based presentation describes the pathophysiology of ocular chemical burns (alkali and acid), as well as the evidence behind currently recommended medical and surgical treatment options.

1. Ocular Chemical Burns
Pathophysiology and Evidence-Based Treatment
Prepared and presented by
Steven M. Christiansen, MD
October 2, 2014
Presentation Day#1 Day#6

2.  Objectives
 Understand pathophysiology and classification of chemical burns
 Understand treatment of chemical burns
▪ Morgan Lens
▪ Medical Treatment
▪ ProKera Ring
▪ Amniotic membrane transplantation
▪ Limbal stem cell transplantation
▪ Tenonplasty
▪ Possible future treatments

3.  Alkali
 Incidence greater than 2x that of acid burns
 76% male, 24% female
 90% accidental, 10% chemical assault
▪ Industrial, agricultural, and household accidents
 Most common causes: ammonia (NH3), lye (NaOH), potassium
hydroxide (KOH), magnesium hydroxide [MG(OH)2], lime [Ca(OH)2]
lye (NaOH) ammonia (NH3) magnesium hydroxide
[MG(OH)2]
lime [Ca(OH)2]

4.  30 year-old male transferred from OSH with 3-day history of
chemical burn
 “Picked up bottle of drain cleaner and didn’t realize lid was off.”
 Pain began 30 minutes later; OTC irrigating kit and OTC triple
antibiotic ointment at night
 3 days later family urged to seek medical care
 ED at OSH irrigated with saline; pH reportedly neutral at transfer

5. Note the chemosis, 3+ injection, diffuse
corneal edema and haze, significant epithelial
defect, layering hypopyon, nasal limbal
whitening, medial canthus whitening with
possible necrosis, and loss of iris details

7. Four successive pH
tests yielded a pH
of approximately 8
Control testing of
pH paper using
sterile water with
known pH of 5.5

8. During Morgan's third Vietnam War tour as a volunteer physician, he concluded that many serious eye problems
developed in individuals because fairly simple infections had not been treated adequately and that a means for delivering
constant irrigation or medication could decrease such infections. In February 1969, in Vinh Long, Morgan molded a
simple device for cleaning the eye. Morgan was familiar with contact lenses (wearing them himself and often prescribing
them to his patients), and his first Morgan Lens was larger than a modern contact lens, resembling the early contact
lenses of the 1940s. His invention is known today as the Morgan Lens, and is used in many Emergency Departments to
provide constant ocular irrigation following chemical injuries. http://www.youtube.com/watch?v=zmXqunkuVR4

10.  Severity of ocular injury is related to surface area and degree
of penetration (alkali>acids)
The hydroxide ion saponifies fatty acid components of cell membranes,
resulting in cell disruption and death, while the cation is responsible for
penetration of the specific alkali

11.  Hydration of the glycosaminoglycans within the corneal
stroma results in loss of clarity
Above is a slit lamp photo of the patient
prior to fluorescein staining. Note the
significant haze and loss of clarity

12.  Hydration of collagen fibrils results in thickening and shortening
causing distortion of the trabecular meshwork
 Release of prostaglandins are responsible for the elevation in IOP
often seen immediately following alkali injuries

13.  Damage to the ciliary body epithelium results in decreased secretion of
ascorbate and a reduction in anterior chamber concentration
 Ascorbate is required by corneal keratocytes to synthesize collagen and repair stroma
In a 1980 article published in Ophthalmology, authors found
that severe ocular alkali burns in rabbits results in a decrease
in aqueous humor ascorbate levels to 1/3 normal levels and
that this deficiency can be reversed by immediate treatment
with parenteral or topical ascorbate. Avoiding ascorbate
deficiency decreases corneal ulceration by providing
sufficient ascorbic acid to fibroblasts for collagen synthesis

14. Stem cells in the limbus divide to produce a daughter stem cell and a transient amplifying cell. These
transient amplifying cells migrate within the cornea to lie in basal layer of corneal epithelium.
Further cellular divisions of transient amplifying cells produce postmitotic cells, which lie in the
suprabasal layers. Progressive differentiation of postmitotic cells produce terminally differentiated
cells, which lie in the superficial corneal epithelial layers. These terminally differentiated cells are
non-keratinized, stratified squamous corneal epithelial cells. These cells are continually sloughed
away from the corneal surface and replaced by maturing, underlying cell layers.
http://www.eophtha.com/eophtha/Anatomy/anatomyofcornea4.html

15.  Limbal and Conjunctival stem cells resurface chemically injured corneal epithelium
 Conjunctival stem cells (as opposed to limbal stem cells) never fully transdifferentiate to corneal
epithelium and may be associated with:
▪ Delayed reepithelialization, superficial and deep stromal vascularization, persistence of goblet cells, and poor
epithelium-basement membrane adhesion
 Limbal stem cells recreate corneal surface (ideal) while conjunctival stem cells repair the epithelial
defect (good) but leave vascularization and fibrosis (less than ideal, causing poor vision following
reepithelialization

16.  Keratocytes responsible for maintenance and regeneration
 Keratocytes may break down collagen via collagenase or synthesize collagen
▪ Matrix metalloproteinases active during remodeling
▪ Excessive degradation via MMP-1 and MMP-8 may lead to sterile corneal
ulceration
▪ Goal = shift balance toward synthesizing, not degrading collagen

17.  Within 12-24 hours, PMNs and mononuclear cells accumulate, leading to
degranulation and release of MMP-8, also known as type 1 collagenase
 Debridement of necrotic conjunctiva eliminates a source for continuous
leukocyte infiltration

18. Grade 1
Little or no loss of limbal
stem cells* or limbal
ischemia
Grade 2
Subtotal loss of limbal
stem cells and ischemia<
½ limbus
Grade 3
Total loss of limbal stem cells,
preservation of proximal
conjunctival epithelium, and
ischemia <1/2 limbus
Grade 4
Total loss of limbal stem cells,
loss of proximal conjunctival
epithelium, with damage to
entire anterior segment
*Extent of limbal stem cell loss can be estimated only after weeks of observation (unless
stem cell stains readily available)

19.  Acute (0-7 days)
 Monitor IOP, inflammation, reepithelialization
 Little to no collagenolytic activity during this phase
 Early Repair (7-21 days)
 Grade I, II reepithelialization continues slowly
 Grade III, IV no reepithelialization due to loss of limbal stem cells
 Second wave of inflammatory cell infiltration with progressive inflammation as long as
epi defect persists
 Late Repair (day 21 to several months later)
 By day 21, inflammation, collagen synthesis, and collagenase activity at highest levels
 Grade I - complete reepithelialization
 Grade II - with sectoral epi defect due to sectoral loss of limbal stem cells; conjunctiva
may epithelialize; fibrovascular pannus
 Grade III - conjunctival epithelialization with fibrovascular pannus resulting in
tectonically stable but scarred and vascularize cornea
 Grade IV – conjunctival epithelialization; ischemic necrosis, may develop cicatricial
entropion, symblepharon

20.  Topical
 Corticosteroids Q1-Q2H
 Medroxyprogesterone Q2H
 Sodium ascorbate 10% Q2H
 Sodium citrate 10% Q2H
 Tetracycline 1% ointment QID
 Cycloplegia as needed
 IOP control as needed
 Systemic
 Doxycycline 100 mg BID
 Sodium ascorbate 2 grams QID
The Wagoner Chemical Injury
Protocol as explained in the Iowa
Ophthalmology Residency
On-Call Survival Guide
*Not included in most recently updated protocol

21.  Topical
 Corticosteroids Q1-Q2H
▪ Decrease inflammation
 Medroxyprogesterone
This study, published in IOVS in 1977 described a substantial reduction in perforation and
deep ulceration of the alkali-burned rabbit cornea by topical or parenteral
medroxyprogesterone. However, medroxyprogesterone has also been shown to suppress
corneal neovascularization and minimally suppress stromal wound repair. Some authors
recommend substituting corticosteroids for medroxyprogesterone after 10-14 days to
minimize interruption of stromal repair.

22.  Topical and Systemic
 Sodium ascorbate is involved in collagen synthesis
 Treating with sodium ascorbate minimizes deficiency and enables
corneal repair

23.  Topical
 Sodium citrate
▪ Calcium required for chemotaxis,
phagocytosis, and enzymatic
release from PMNs
▪ Citrate chelates calcium This 1984 study published in
Experimental Eye Research
found that topical sodium
citrate inhibited PMN
infiltration and corneal
ulceration

24.  Systemic Doxycycline
▪ Tetracyclines
▪ restrict gene expression of neutrophil collagenase
▪ suppress 1-antitrypsin degradation
▪ scavenge reactive oxygen species
This study, published in 2000 reported that
tetracyclines inhibit matrix metalloproteinases
by mechanisms independent of their
antimicrobial properties, primarily through
restriction of the gene expression of
neutrophil collagenase and epithelial
gelatinase, suppression of 1-antitrypsin
degradation, and scavenging of reactive
oxygen species.

25.  Topical
 Corticosteroids Q1-Q2H
 Medroxyprogesterone Q2H
 Sodium ascorbate 10% Q2H
 Sodium citrate 10% Q2H
 Tetracycline 1% ointment QID
 Cycloplegia as needed
 IOP control as needed
 Systemic
 Doxycycline 100 mg BID
 Sodium ascorbate 2 grams QID
*Not included in most recently updated protocol

26. Note the increased injection throughout the conjunctiva, as well as the ischemic
limbal whitening. In the bottom left photo, note the partial reepithelialization from
about 10 to 4 o’clock, suggestive of persistent limbal stem cells in this area

28.  Amniotic membrane
 Thin, semitransparent innermost layer of fetal membrane; avascular stroma, basement membrane,
and epithelium
 Requires at least partial limbal stem-cell function
 Reepithelialization facilitated by providing a basement membrane to which epithelium may adhere
and promoting proliferation of limbal stem cells and transient amplifying cells via growth factors
within transplanted membrane
 Orientation dictates area of epithelialization
 If basement membrane oriented towards eye, acts as an ‘onlay’ patch graft, promoting
epithelialization beneath membrane
 If basement membrane oriented away from eye, acts as an ‘inlay’ graft, with amniotic membrane
functioning as new basement membrane, promoting epithelialization above the graft
 Can also create amniotic membrane sandwich with basement membranes oriented towards each
other to promote reepithelialization between the two basement membranes
 Successful reepithelialization reported in grade II and III injuries; disappointing results in grade IV
injuries

29. Amniotic membrane transplantation can be
performed using a ProKera Ring, which is
essentially amniotic membrane within a ring-shaped
material that can then be placed over
the cornea much like a scleral contact lens.
If a larger surface area needs to be covered,
many surgeons prefer free amniotic
membrane transplantation, which must be
performed in the OR. This often takes place
following use of a ProKera Ring.

30. Note the complete ischemia from 6:30 to 11:00, caruncle and nasal conjunctival necrosis,
and scleral melting nasally. Also note the persistent but healing corneal epithelial defect.

31.  Tenonplasty
 Use healthy, vascularized tissue to reduce necrosis, promote
reepithelialization
 Debride devitalized conjunctiva, advance Tenon’s capsule to limbus

32.  Limbal stem cell transplantation
 Only method of reestablishing phenotypically correct corneal epithelial surface in grade
III or IV injuries to avoid fibrovascular pannus (III) or sterile corneal ulceration (IV)
https://www.youtube.com/watch?v=3v1FGY2yhQY

33.  Boston Keratoprosthesis
 A good option for patients who have failed prior medical and surgical
therapy
 Wynn Institute for Vision Research at the University of Iowa
 Hoping to develop a method for harvesting residual stem cells from patients with bilateral eye injuries with loss of stem cells,
culturing the enriched populations and implanting the stem cells back to the same patient at a later date, which would prove a
great benefit over the current treatment which involves use of cadaver stem cells which often end up rejecting despite
aggressive immunosuppression.

34. Presentation Day#1 Day#6
Thank you

35. References
1. Wagoner MD. Chemical injuries of the eye: current concepts in pathophysiology and
therapy. Surv Ophthalmol. 1997 Jan-Feb;41(4):275-313. Review. PubMed PMID: 9104767.
2. The Morgan Lens for Eye Irrigation. YouTube.
http://www.youtube.com/watch?v=zmXqunkuVR4. Accessed 10/6/14
3. Pfister RR, Paterson CA. Ascorbic acid in the treatment of alkali burns of the eye.
Ophthalmology. 1980 Oct;87(10):1050-7. PubMed PMID: 7243199.
4. Newsome NA, Gross J. Prevention by medroxyprogesterone of perforation in the alkali-burned
rabbit cornea: inhibition of collagenolytic activity. Invest Ophthalmol Vis Sci. 1977
Jan;16(1):21-31. PubMed PMID: 188776.
5. Paterson CA, Williams RN, Parker AV. Characteristics of polymorphonuclear leukocyte
infiltration into the alkali burned eye and the influence of sodium citrate. Exp Eye Res.
1984 Dec;39(6):701-8. PubMed PMID: 6097468.
6. Ralph RA. Tetracyclines and the treatment of corneal stromal ulceration: a review. Cornea.
2000 May;19(3):274-7. Review. PubMed PMID: 10832682.
7. Clare G, Suleman H, Bunce C, Dua H. Amniotic membrane transplantation for acute ocular
burns. Cochrane Database Syst Rev. 2012 Sep 12;9:CD009379. doi:
10.1002/14651858.CD009379.pub2. Review. PubMed PMID: 22972141.
8. The Wagoner Chemical Injury Protocol. Principles and Practice of Ophthalmology, 3rd
Edition. Volume 1, Chapter 56, page 761.
9. Tenonplasty for Scleral Ischemia. YouTube.
https://www.youtube.com/watch?v=3v1FGY2yhQY. Accessed 10/6/14.