CASE REPORT
Treatment of Lisch Corneal Dystrophy With
Photorefractive Keratectomy and Mitomycin C
Matthew M. Wessel, MD,* Jayati S. Sarkar, MD,* Frederick A. Jakobiec, MD, DSc,
Natasha Dang, MD, Pooja Bhat, MD, Norman Michaud, BS, and Christopher E. Starr, MD, FACS*
Purpose: To describe a case of Lisch dystrophy; review the clinical,
histopathologic, and electron microscopic features of this entity; and
discuss a novel treatment approach using photorefractive keratectomy
(PRK) and mitomycin C (MMC).
Methods: A 45-year-old man with a feathery, comet-shaped, right-
sided, corneal lesion was treated with excimer laser PRK and 20
seconds of MMC. The uninvolved fellow eye underwent traditional
PRK without the use of MMC. Epithelial scrapings were sent for
histopathologic analysis.
Results: Histopathologic analysis showed vacuolated cells in the
epithelial layer. Electron microscopy revealed empty intracytoplasmic
vacuoles, electron-dense whorled inclusions, and reduced tonofila-
ments. Surface ablation and MMC was successful in treating the
initial lesion, with only minimal recurrence noted in the affected eye.
Surprisingly, a new asymptomatic lesion was noted in the unaffected
eye but dissipated over time.
Conclusions: Although the whorled inclusions represent a novel
finding, the overall clinical and microscopic analysis was consistent
with Lisch dystrophy. Surface ablation with MMC should be
considered as a treatment option for this disease.
Key Words: Lisch corneal dystrophy, photorefractive keratectomy,
mitomycin C, electron microscopy
(Cornea 2011;30:481485)
L isch dystrophy was first reported in 1992 by Lisch et al1
who described unilateral and bilateral, gray, band-shaped,
and feathery opacities that sometimes appear in whorled
patterns in a series of 5 family members and 3 nonrelated
Received for publication March 25, 2010; revision received May 31, 2010;
accepted June 2, 2010.
From the *Department of Ophthalmology, New York-Presbyterian Hospital,
Weill Cornell Medical College of Cornell University, New York, NY;
David G. Cogan Laboratory of Ophthalmic Pathology, Massachusetts
Eye and Ear Infirmary of Harvard Medical School, Boston, MA; and
Department of Ophthalmology, University of Ottawa Eye Institute of the
Ottawa Hospital, Ottawa, ON.
The authors state that they do not have any proprietary interest in this study.
Reprints: Christopher E. Starr, Department of Ophthalmology, New York-
Presbyterian Hospital, Weill Cornell Medical College of Cornell
University, 1305 York Avenue, 11th Floor, New York, NY 10021
(e-mail: cestarr@med.cornell.edu).
Copyright 2011 by Lippincott Williams & Wilkins
Cornea  Volume 30, Number 4, April 2011
patients. Retroillumination of the opacities revealed densely
crowded intraepithelial cysts. Further examination with
light and electron microscopy revealed diffuse vacuolization
of the affected epithelial cells. Although apparently clinically
distinct, Lisch dystrophy was found to be genetically unique in
2000 when Lisch et al2 presented evidence linking the gene for
Lisch corneal dystrophy to Xp22.3, on the basis of a study of
48 family members.
Despite 17 years since Lisch corneal dystrophy was first
described, the literature on the subject remains limited. Reports
by Robin et al,3 Charles et al,4 Alvarez-Fischer et al,5 and Lisch
et al6 have described additional cases. Treatment options
consisted of topical therapy (lubricants and steroids), epithelial
scraping, and contact lenses, with mostly limited success
because recurrence is common. The intent of this article was to
describe a recent case of Lisch corneal dystrophy and its
histopathologic and confocal microscopy findings and to
describe a novel and successful treatment option.
CASE REPORT
Presentation
A 45-year-old white man presented with a 3-week history of
glare, blurred vision, and a film affecting his right eye. Ophthalmic
history was unremarkable except for mild myopia, early presbyopia,
and daytime wear of soft contact lenses in both eyes. Significant
medical history included hypertension and colonic resection
secondary to diverticulitis. He was not using any medications. He
was a nonsmoker with a history of social alcohol use. Family history
was negative for known ophthalmic disease.
On examination, best-corrected visual acuity was 20/20 in
both eyes; however, the visual quality and reading speed of the right
eye was noticeably worse than the left. Manifest refraction was 1.75
sphere OD and 2.00 sphere OS. On slit-lamp examination, there was
mild conjunctival injection with 0.5 mm of 360-degree limbal pannus
bilaterally. A nonstaining, epithelial, comet-shaped, gray opacity
extending from the limbus to the central cornea was noted in the right
eye (Fig. 1). The rest of the eye examination was otherwise within
normal limits. Confocal microscopy (ConfoScan 4; Nidek Technol-
ogies, Padova, Italy) was performed and demonstrated nonspecific
intraepithelial hyperreflectivity in the context of a normal corneal
stroma, endothelium, and nerves (Fig. 2).
Because his symptoms were new and only involved his right
eye, it was initially diagnosed as a contact lensrelated nonspecific
epitheliopathy. Contact lens wear was discontinued, and the patient
was started on topical medications including artificial tears and
steroids. After a month of topical therapy, there was no change in the
appearance of the lesion or his symptoms. At this point, it was
apparent that the clinical findings were most consistent with Lisch
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Wessel et al
FIGURE 1. A comet-shaped opacity consisting of densely
crowded cysts can be seen extending toward the center of the
cornea of the patients right eye. The cornea of the left eye (not
shown here) was unremarkable.
dystrophy, and topical therapy was discontinued. Despite resuming
soft contact lens wear at this time, the patient remained dissatisfied
with his vision, and alternative therapy was discussed.
In an attempt to treat the dystrophy and achieve spectacle
independence for distance vision, the patient chose to undergo
photorefractive keratectomy (PRK) in both eyes. The procedure on
the right eye involved instillation of topical tetracaine followed by
removal of the central 9 mm of epithelium without the use of alcohol.
Care was taken to remove the involved epithelium in a sheet, and it
was placed in formalin and sent for histopathologic analysis.
Because of poor HartmannShack imaging through the
dystrophy, a traditional nonwavefront ablation was performed (VISX
S4 laser) followed by the application of mitomycin C (MMC) 0.02%
for 20 seconds to the central cornea. The MMC-soaked sponge was
also briefly applied to the peripheral cornea and limbus at 10:00 in the
area of the epithelial dystrophy. After application of MMC, the cornea
was vigorously rinsed with Balanced Salt Solution, and a soft
bandage contact lens (Acuvue Advance, base curve 8.6) was placed
followed by several drops of a steroid (PredForte), an antibiotic
FIGURE 2. In vivo confocal microscopy of the corneal
epithelium showing nonspecific intraepithelial hyperreflectivity.
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Cornea  Volume 30, Number 4, April 2011
(Zymar), and a non-steroidal anti-inflammatory (Acular LS). The left
eye then underwent wavefront-guided PRK with iris registration,
alcohol was used to facilitate epithelial removal, and no MMC was
applied. Our standard postoperative regimen of a topical steroid
(fluoromethalone, 4 times per day in both eyes for 1 month and then
tapering off over the following 46 weeks), cyclosporine A (0.05%
twice per day in both eyes for 6 months), topical antibiotics
(gatifloxacin, 4 times per day for 1 week), and oral vitamin C (2000
mg, by mouth daily for 2 weeks) was followed.
Clinical Results
The immediate postoperative course of the patient was
uneventful. By postoperative day 4, the epithelium in both eyes
had healed and there was no evidence of a corneal dystrophy in either
eye. At the 4-week postoperative visit, however, an early recurrence
of Lisch dystrophy was noted in the right eye and a similar lesion was
now apparent in the left eye for the first time. These lesions were
watched closely over the next few months, and by postoperative
month 7, they had substantially regressed. In the right eye, despite
appearing in a similar location as the initial lesion, the new lesion was
only a faint linear opacity covering not more than a tenth of the
surface area of the initial lesion (Fig. 3A). The opacity in the left eye
had a similar size and distribution, and neither of the lesions
demonstrated any effect on vision (Fig. 3B). By postoperative month
13, further regression was noted, especially in the left eye where only
a faint wisp of the new lesion was noted near the limbus (Figs. 3C, D).
The patient had an uncorrected visual acuity of 20/15 in each eye and
had no visual complaints of glare or a film over his vision. His
manifest refraction was plano OD and 20.25 D sphere OS.
Pathologic Findings
After receiving the specimen for histopathologic evaluation,
the affected right corneal epithelium was fixed in glutaraldehyde,
embedded in epon, and stained with toluidine blue. The basal cells
did not display any adherent stroma indicative of a pannus and
exhibited a cuboidal appearance without any detectable mitotic
figures. The nuclei were round to oval with an inconspicuous
nucleolus and a low nuclear to cytoplasmic ratio. In the suprabasal
and parabasal layers, there were vacuolated cells that worked their
way to the surface of the epithelial layer, where they adopted
elongated flat squamous shapes (Fig. 4A). Parakeratin, orthohyper-
keratosis, and intercellular cysts were not identified.
Transmission electron microscopy disclosed the presence of
unremarkable basal germinal cells with an intact basement membrane
and associated hemidesmosomes. Bundles of tonofilaments, scattered
mitochondria, and short profiles of rough surface endoplasmic
reticulum were observed. In the midlevel of the epithelium and
progressing toward the surface, there were cells with myriad vacuoles
and inclusions. These assumed 1 of 2 forms: those with vaguely
flocculent or lamellar material (Fig. 4B) with or without a circum-
scribing membrane, and more electron-dense whorled or membra-
nous structures (Fig. 4C). The most superficial cells had rarefied
degenerating cytoplasm with mostly vestiges of the electron-dense
whorled inclusions (Fig. 4D). The involved cells predominantly
contained one or the other type of inclusion, but there were those that
had compound inclusions with both lamellar-flocculent and whorled
components (Figs. 5A, B). Sparser tonofilaments were identified in
the cells with the inclusions; intercellular desmosomes connected the
involved cells with neighboring keratinocytes lacking inclusions.
Large interepithelial spaces were not detected.
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FIGURE 3. A, At postoperative
month 7, a faint linear opacity
covering not more than a tenth of
the surface area of the initial lesion
can be seen in the right eye. B, The
left eye, previously unaffected, now
shows a similar lesion to the right
eye. C, D, The lesions at postoper-
ative month 13, right eye (C) and left
eye (D)note that the lesion in the
left eye has nearly completely re-
gressed and is only a faint wisp near
the limbus (arrow).
DISCUSSION
Lisch epithelial dystrophy remains a rare clinical entity with
unique morphologic, histopathologic, and genetic characteristics
that distinguish it from other superficial corneal dystrophies
including Meesmann dystrophy, bleb corneal dystrophy, advanc-
ing wave-like epitheliopathy, and Fabry disease. The epithelial
bubbles in Meesmann are bilateral and diffuse7 unlike the crowded
cysts seen in our patient. The blebs described by Bron and Brown8
can only be seen on retroillumination, are associated with erosions
similar to map-dot-fingerprint, and do not contain intracytoplas-
mic vacuolescharacteristics not found in our patient. Advancing
wave-like epitheliopathy does not demonstrate microcysts on
histopathology.9 Finally, Fabrys disease or certain medications can
cause corneal verticillata, which appear as ultrafine dots with lipid
inclusions, unlike the larger microcysts of our patient.
Given the rare nature of Lisch dystrophy, there are only
a few case reports that discuss treatment outcomes for this
condition. In his original article, Lisch performed therapeutic
epithelial abrasions in 3 patients, and despite treatment, the
lesions recurred and the vision dropped to their pretreatment
levels. The corneal changes were progressive in 2 patients but
regressed in another with hard contact lens wear. Robin et al3
treated their symptomatic patient with epithelial debridement,
but this led to recurrence and progression. Subsequent treat-
ment with a rigid gas-permeable contact lens led to partial
regression. Charles et al4 used epithelial scraping as well, and
like the previous reports, recurrence was noted. While
Alvarez-Fischer et al5 reported a case of Lisch dystrophy
treated with scraping of the corneal epithelium, the patient was
only reexamined after 6 months of follow-up. Most recently,
Lisch et al6 reported after successfully treating 2 patients with
the use of soft contact lenses. Our patient, however, was
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Lisch Corneal Dystrophy
a regular soft contact lens wearer when the dystrophy first
became symptomatic. Even after stopping soft lenses for
a month and then resuming full-time wear, there was no
change noted in the patients corneal dystrophy.
To the best of our knowledge, ours is the first-reported
case in the English literature to use MMC in addition to
excimer laser PRK in the treatment of Lisch dystrophy. MMC
is an alkylating agent and has gained acceptance in certain
ophthalmic surgeries including pterygium excision, trabecu-
lectomy, and PRK. Given that it inhibits keratocyte prolifera-
tion and induces keratocyte apoptosis,10,11 it has been used to
prevent the development of haze after PRK and other surface
ablation techniques.12 Although the pathogenesis of Lisch
dystrophy is unknown, it was speculated that the addition of
MMC could potentially prevent recurrence of the lesion
through similar biochemical processes that have rendered it
successful in the aforementioned procedures. Although not
completely eradicating the lesion in our patient, the combina-
tion of PRK and MMC led to over a 90% regression of the
initial lesion and a complete reversal of the visual disturbance.
In patients who do not desire a refractive correction, PTK with
or without MMC could be a suitable alternative.
Although we cannot conclusively say PRK with MMC
was solely responsible for our successful outcome, considering
that there have been almost no successful treatments in the
literature despite a multitude of attempts, we believe this
combination could represent a novel treatment approach for
Lisch dystrophy. More cases are needed to validate its success.
We would finally like to point out that there were 2
unique findings in our patient. First, on electron microscopy,
there were electron-dense whorled inclusions in addition to
empty vacuoles. This feature had not previously been
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Wessel et al Cornea  Volume 30, Number 4, April 2011

FIGURE 4. A, A strip of corneal

epithelium in which vacuolated cells
begin to appear at the midlevel and
migrate toward the surface (arrows)
(1-mm plastic section, toluidine blue
3400). B, A subapical keratinocyte
contains multitudinous cytoplasmic
inclusions that have displaced the
nucleus (N) inferiorly (transmission
electron microscopy 33400). C, A
viable keratinocyte contains whorled
electron-dense cytoplasmic inclu-
sions (37900). D, Superficial cells
display granular degeneration of the
cytoplasm and contain electron-
dense whorled inclusions. Note the
presence of inclusions in the most
superficial cell layer (SL) where
desquamation is about to occur
(310500).

described in any of the prior studies. The exact pathogenesis of cytoplasmic rarefraction and reduced tonofilaments. Finally,
these inclusions is unknown, but it is possible that they it is worth noting that the unaffected eye demonstrated a new
represent a new variant of Lisch dystrophy. No intraepithelial lesion after PRK without MMC that clinically resembled the
intercellular cysts were discovered by light and electron lesion in the affected eye. Given that Lisch dystrophy has been
microscopy. The clinical appearance of cysts is probably mapped to the X chromosome and demonstrates a trans-
because of clusters of epithelial cells with vacuolar missible pattern, it is possible that the corneas of affected

FIGURE 5. A, Most of the cytoplas-

mic vacuoles in this cell contain
flocculent or vaguely membranous
structures (310500). B, Complex
cytoplasmic inclusions display mem-
branous whorled bodies of various
electron densities associated with
more flocculent and electronlucent
material (319000).

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Cornea  Volume 30, Number 4, April 2011
individuals are predisposed to develop the dystrophy and that
some type of insult might be necessary for either instigation or
spread of the lesion. Further investigation is necessary.
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3. Robin SB, Epstein RJ, Kornmehl EW. Band-shaped, whorled microcystic
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Cornea. 2005;24:494495.
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