Cornea 19(2): 135–139, 2000. © 2000 Lippincott Williams & Wilkins, Inc.

, Philadelphia

Penetrating Keratoplasty for Varicella-Zoster

Virus Keratopathy

Marco Antonio G. Tanure, M.D., Elisabeth J. Cohen, M.D.,

Sanjeev Grewal, M.D., Christopher J. Rapuano, M.D., and
Peter R. Laibson, M.D.

Purpose. To examine and report the results of penetrating kera-
toplasty performed in patients with varicella-zoster virus ker-
atopathy. Methods. The authors retrospectively reviewed the
records of 15 patients who had penetrating keratoplasty for
varicella-zoster virus keratopathy from January 1989 through
December 1998 on the Cornea Service at Wills Eye Hospital.
Results. Twelve patients had a preoperative diagnosis of herpes
zoster ophthalmicus, and three, of varicella. Four eyes had
lateral tarsorrhaphies performed in conjunction with penetrat-
ing keratoplasty. Three eyes had endothelial rejection episodes
that responded well to treatment with topical steroids. One eye
had a regraft 1 month after primary failure, and this second
graft also failed because of recurrent neurotrophic keratopathy.
Three eyes that had repeated penetrating keratoplasty for graft
failure had clear grafts at the last examination. At an average
follow-up time of 50 months, 13 (86.7%) grafts remained clear,
and the best corrected visual acuity was 20/100 or better in
eight (53.3%) eyes. Five patients had decreased visual acuity
because of retinal diseases. Conclusion. Although varicella-
zoster virus keratopathy is an uncommon indication for pen-
etrating keratoplasty, effective visual rehabilitation can be
achieved in these patients. Careful postoperative management,
frequent lubrication, and lateral tarsorrhaphies to protect the
corneal surface are major factors in the successful outcome of
these cases. Key Words: Penetrating keratoplasty—Varicella-
zoster virus—Herpes zoster ophthalmicus.
The occurrence of ocular involvement in patients with
herpes zoster ophthalmicus (HZO) is between 50 and
70% (1,2). Varicella-zoster virus (VZV) infection can
involve nearly any ocular structure, and corneal involve-
ment is one of the leading causes of visual impairment in
these eyes (3–7). VZV keratopathy is present in 50–75%
of patients with ocular disease and can range in severity
from mild disease, such as corneal pseudodendrites, to
Submitted May 28, 1999. Revision received July 28, 1999. Accepted
July 29, 1999.
From the Cornea Service, Wills Eye Hospital, Jefferson Medical
College, Philadelphia, Pennsylvania, U.S.A.
Address correspondence and reprint requests to Dr. E.J. Cohen, Cor-
nea Service, Wills Eye Hospital, 900 Walnut Street, Philadelphia, PA
19107, U.S.A.
eye-threatening conditions such as perforated neuro-
trophic ulceration (1,4,6,7).
Penetrating keratoplasties (PKs) performed in eyes
with sequelae of VZV infection are considered to be at
increased risk of failure, and are therefore commonly
performed for tectonic purposes only (3,4). Previous
studies of the clinical indications for PK performed in
major referral centers show that only a small proportion
of transplants are done for VZV keratopathy (8–12). Be-
tween January of 1989 and December of 1995, only 11
(0.5%) of 2,186 corneal transplants carried out at the
Wills Eye Hospital were performed on eyes affected by
VZV (13). Despite encouraging results in some publica-
tions (10,14,15), there is a tendency for surgeons to avoid
operating on eyes with VZV involvement.
The purpose of this study was to examine and report
the results of PKs performed in patients with corneal
lesions secondary to VZV infection during a 10-year
period on the Corneal Service at Wills Eye Hospital.
PATIENTS AND METHODS
A retrospective chart review was conducted of all pa-
tients undergoing PK at Wills Eye Hospital for sequelae
of VZV infection between January 1989 and December
1998. All surgeries were performed by four surgeons on
the Corneal Service using similar surgical techniques.
Patients were excluded if they had <6 months of post-
operative follow-up.
The diagnosis of HZO or varicella was established
from clinical information in the patients’ records. Demo-
graphic data, time interval between initial ocular involve-
ment and surgery, indication for surgery (tectonic or vi-
sual), preoperative and postoperative best-corrected vi-
sual acuity (BCVA), degree of vascularization, duration
of follow-up, and graft clarity at the last examination
were all recorded. Any associated procedures in the pre-
operative, perioperative, or postoperative periods were

135
136 M.A.G. TANURE ET AL.
also noted. Underlying causes for poor vision in patients
with BCVA <20/40 at the final assessment with good
graft clarity were examined. Preoperative corneal vascu-
larization was graded as follows [adapted from Cobo et
al. (16)]:
1. avascular or superficial vessels only;
2. deep vascularization in one to three quadrants; or
3. deep vascularization in all four quadrants.
All PKs were performed with donor grafts oversized
by 0.25–0.50 mm except in one case, in which both
donor and recipient trephination were 9.0 mm in diam-
eter. After a partial-depth trephination, the anterior
chamber was entered with a blade, and the corneal button
was excised with corneal scissors. In all cases, donor
trephination was performed with the endothelial surface
up. Interrupted 10-0 nylon sutures or combined inter-
rupted and running sutures were used. All patients who
required cataract extraction, whether concomitant with
the PK or at a later date, had extracapsular surgery or
phacoemulsification with posterior chamber lens implan-
tation. Tarsorrhaphy was performed in eyes with eyelid
abnormalities or with history of neurotrophic keratitis to
provide additional protection for the grafts in the post-
operative period. At the conclusion of surgery, all pa-
tients were administered subconjunctival betamethasone,
gentamicin, and cefazolin (or vancomycin, if allergic to
penicillin).
Postoperatively, topical prednisolone acetate, 1%, was
administered 4 to 6 times daily initially, with a gradual
taper. All patients also received topical antibiotic drops
or ointment for the immediate postoperative period.
Bland antibiotic ointment (e.g., erythromycin) was con-
tinued during topical steroid therapy to protect the cor-
neal surface. Antiviral therapy was not used in any case
postoperatively. Elevated intraocular pressure in the pre-
operative or postoperative period was treated with topi-
cal and systemic aqueous suppressant therapy as needed.
The frequency of postoperative care was scheduled on a
case-by-case basis, and each visit included measurement
of visual acuity, intraocular pressure, and slit-lamp bio-
microscopy with and without fluorescein dye.
For the purpose of this study, graft rejection was de-
fined as the biomicroscopic appearance of an epithelial
rejection line, subepithelial infiltrates, and/or an endo-
thelial rejection line. Anterior chamber reaction, keratic
precipitates, or graft edema in the absence of these find-
ings was analyzed separately, because it could be indica-
tive of recurrent disease or graft failure without rejection.
Rejection episodes were treated with frequent topical
prednisolone acetate, 1%. Graft failure was defined as
irreversible corneal edema after initial graft clarity. Irre-
versibly edematous grafts with no period of initial clarity
were considered primary graft failures.
Cornea, Vol. 19, No. 2, 2000
RESULTS
Fifteen patients (15 eyes) underwent 18 PKs during
the study period (Table 1). All of these patients met the
inclusion criteria. Twelve (80%) of the 15 eyes had cor-
neal disease secondary to HZO, and three of the eyes
(cases 1, 4, and 12) were affected by varicella. Twelve
were female, and three were male patients. The mean age
of patients at the time of surgery was 57.4 years, with a
range from 4 to 83 years (Fig. 1). The mean age of
patients with HZO (66.9 years) was much greater than
that of those with varicella (19.3 years). The time inter-
val between initial ocular involvement and PK ranged
from 10 months to 41 years, with a mean of 10.1 years.
Two thirds of the eyes had deep corneal vascularization
at the time of surgery (Table 2), and two eyes (cases 9
and 13A) had preoperative argon laser cauterization of
the deep vessels. Four eyes were pseudophakic. The in-
dication for PK in 11 patients was visually significant
scarring from previous keratitis, with or without lipid
deposition. Three eyes (cases 2, 7, and 10A) had corneal
scarring due to prior neurotrophic ulceration, and one
patient (case 15) required PK for a recurrent, perforated,
neurotrophic ulceration in a 5-month old graft performed
elsewhere. Preoperative BCVA was counting fingers or
less in 46.7% of the eyes (Fig. 2), and mean intraocular
pressure before PK was 14 mm Hg (range, 9–21 mm
Hg). Two patients (cases 8 and 9) required ocular hypo-
tensive agents preoperatively. Four (26.7%) eyes under-
went cataract extraction with posterior chamber intraoc-
ular lens implantation concurrent with the PK. One pa-
tient (case 14) required cataract extraction and lens
implantation 30 months after the PK, and another patient
(case 11) required an Nd:YAG laser capsulotomy 12
months after PK and cataract extraction with intraocular
lens implantation. Tarsorrhaphy was performed at the
time of PK in four eyes, with two being temporary (cases
3 and 13) and the others (cases 10 and 15) permanent.
One patient underwent punctal occlusion with a silicone
plug (case 15).
The mean follow-up after PK was 50 months (range,
9–110 months).
In four (26.7%) eyes, subepithelial infiltrates occurred
at some point during the postoperative course, and in
three (20%) patients, endothelial rejection was observed
(Table 2). Endothelial rejection was associated with deep
corneal vascularization (grade II in cases 1 and 2; grade
III in case 4). All cases of rejection responded to frequent
topical prednisolone acetate, 1%, therapy. Anterior
chamber inflammatory reaction and/or graft edema in the
absence of an endothelial rejection line occurred in eight
(53.3%) eyes, and all cases responded to frequent topical
steroid treatment.
A total of five (33.3%) patients had graft failure during
the study period, all of them with diagnosis of HZO. One
 VARICELLA-ZOSTER VIRUS KERATOPATHY 137

TABLE 1. Clinical data of patients

Interval
onset ocular Postop.
Patient Age Preop. disease-PK Preop. Type of follow-up Rejection Final graft Preop. Postop. Cause for
(n) (yr) Sex diagnosis (mo) vasculariz. surgery (mo) type (n) clarity VA BCVA VA decrease

1 38 F Varicella 86 II PK 17 End. (2) Clear 20/100 20/25 —

2 71 F HZO 36 II PK 110 End. (1) Failure CF 20/400 K scar,
cataract
3 72 F HZO 492 I PK + TLT 21 No Clear (mild 20/200 20/200 Glaucoma,
central haze) ARMD
4 4 F Varicella 38 III PK 109 SEI (2) Clear CF 20/30 —
End. (3)
5 (A) 19 F HZO 10 I PK 64 SEI (2) Failure 20/40 CF Bacterial
keratitis
5 (B) 25 F HZO 74 II PK 36 SEI (1) Clear CF 20/25 —
6 68 F HZO 180 II PK 41 No Clear 20/70 20/200 ARMD
7 72 M HZO 126 II PK 89 SEI (2) Clear 20/400 20/200 ARMD
8 83 F HZO 128 II PK + CE/IOL 31 No Clear 20/400 20/40 —
9 78 F HZO 36 II PK 54 No Clear (inf. LP 20/70 Irreg. astig.
haze)
10 (A) 73 F HZO 86 II PK + PLT 1 No Failure 20/100 CF K edema
10 (B) 73 F HZO 87 II PK + PLT 50 No Failure CF 20/400 K scar, PC
opacity
11 65 F HZO 84 III PK + CE/IOL 73 No Clear CF 20/40 —
12 16 F Varicella 133 I PK 50 SEI (1) Clear 20/400 20/30 —
13 (A) 80 M HZO 36 II PK + CE/IOL + 51 No Failure CF HM Bacterial
TLT keratitis
13 (B) 84 M HZO 87 III PK + TLT 16 No Clear HM CF CME, irreg.
astig
14 63 F HZO 324 I PK 43 No Clear CF 20/200 Diabetic
retinopathy
15 (*) 59 M HZO 23 I PK + CE/IOL + 9 No Clear LP 20/60 SPE
PLT (trichiasis)

n, number; F, feminine; M, masculine; PK, penetrating keratoplasty; CE/IOL, cataract extraction with intraocular lens implantation; TLT, temporary lateral
tarsorrhaphy; PLT, permanent lateral tarsorrhaphy; BCVA, best-corrected visual acuity; CF, counting fingers; HM, hand movements; LP, light perception;
End., endothelial; SEI, subepithelial infiltrates; K, cornea; ARMD, age-related macular degeneration; PC, posterior capsule; CME, cystoid macular edema;
SPE, superficial punctate erosions; corneal vascularization: I, avascular or superficial vessels only; II, deep vessels in one to three quadrants; III, deep
vessels in all quadrants; (A), first surgery; (B), second surgery; (*), perforated ulcer.

of the failed grafts (case 2) was due to recurrent neuro- spontaneous opening of a tarsorrhaphy in a severely neu-
trophic ulceration in a patient who refused tarsorrhaphy. rotrophic eye, with subsequent entropion, ulceration, and
The result was marked central scarring and vasculariza- ultimately a dense scar in the visual axis.
tion of the graft. In two eyes (cases 5A and 13A), the A total of 13 (86.7%) eyes had clear grafts by slit-lamp
grafts failed after bacterial keratitis developed in the pri- biomicroscopic examination at their final evaluation, and
mary graft, one of them related to a suture abscess (case only two (13.3%) grafts were opaque because of graft
5A). One eye (case 15) had a failed graft and corneal failure (Table 2).
perforation from a neurotrophic ulcer. The other patient BCVA at the final follow-up was improved over pre-
(case 10A) developed primary graft failure and under-
went repeated PK 1 month after his initial PK.
TABLE 2. Patient distribution by peroperative corneal
Four patients were regrafted, and three of them (cases
vascularization, rejection episodes, and final graft clarity
5B, 13B, and 15) had clear grafts at the end of follow-up.
Patient 10 had another graft failure after the early and Variable No. %
Corneal vascularization
I 5 33.3
II 8 53.3
III 2 13.3
Rejection episodes
None 9 60.0
SEI 3 20.0
Endothelial 2 13.7
SEI + endothelial 1 6.3
Final graft clarity
Clear 13 86.7
Cloudy 2 13.3

No, number; SEI, subepithelial infiltrates; corneal vasculariza-

tion: I, avascular or superficial vessels only; II, deep vasculariza-
tion in one to three quadrants; III, deep vascularization in all four
FIG. 1. Patient distribution by age (years). quadrants.

Cornea, Vol. 19, No. 2, 2000

138 M.A.G. TANURE ET AL.
FIG. 2. Preoperative and postoperative BCVA.
operative BCVA in 11 (77.3%) eyes, equal in two
(13.3%) eyes, and worse in two (13.3%) eyes. Eight
(53.3%) eyes had BCVA of ⱖ20/100, and six (40%)
eyes had BCVA of ⱖ20/40 (Fig. 2). All eyes with BCVA
of ⱕ20/200 and clear graft had posterior segment abnor-
malities that accounted for the decreased vision (Table
1). All three cases of varicella had BCVA >20/40.
At the final visit, intraocular pressure ranged from 10
to 18 mm Hg, with a mean of 14 mm Hg. Three patients
(cases 1, 3, and 13) who had steroid-induced elevated
intraocular pressure were using ocular hypotensives as
part of their regimen.
DISCUSSION
This study demonstrates that good results can be
achieved when PK is performed in patients with VZV
keratopathy. During a postoperative period averaging 50
months, 13 (86.7%) of the eyes studied ultimately had
clear grafts, with visual acuity ⱖ20/100 in eight (53.3%)
cases. A few studies in the ophthalmic literature report
the outcome of PK in patients with corneal sequelae of
VZV infection (10,14,15). In a study of nine patients
with corneal scarring due to HZO undergoing PK and
followed up for a mean period of 18 months, Soong et al.
(10) reported clear grafts in 77.8% and final visual acuity
of ⱖ20/50 in 67%. Reed et al. (15) reported clear grafts
in 83% of 12 patients followed up for a mean of 36
months. One third of their patients initially had perfo-
rated neurotrophic ulcers, and two patients had recur-
rence of neurotrophic ulceration in the graft. Final visual
acuity of ⱖ20/80 was found in 75% of their patients.
Marsh and Cooper (14) reported a series of seven pa-
tients followed up for a mean of 67 months, and 85.7%
had clear grafts and visual acuity of ⱖ20/40 at their final
evaluation. This series included only one patient with
neurotrophic ulceration, who went on to develop graft
failure.
Soong et al. (10) suggested that higher success rates
may be achieved by waiting as long as possible after
active inflammation subsides before performing PK. In
our series, the mean interval between onset of disease
and PK was 10 years, and this may play a role in our
Cornea, Vol. 19, No. 2, 2000
success rate. Only one of our patients had active disease
with a perforated ulcer at the time of PK.
We observed only three cases of endothelial rejection
in our series, despite moderate to severe deep corneal
neovascularization (grade II–III) in 67% of the eyes. All
endothelial rejection episodes were treated successfully
with topical steroids. It is noteworthy that all three vari-
cella patients had episodes of rejection, including endo-
thelial rejection in two cases. The high rate of rejection in
varicella patients may be due their relatively young age
and perhaps extent of preoperative neovascularization,
although this was variable. Reed et al. (15) reported two
cases of “mild rejection” that were successfully treated
with topical steroid therapy. One successfully treated
case of rejection was reported by Marsh and Cooper (14).
Soong et al. (10), however, reported two graft failures as
a result of endothelial rejection.
We believe that frequent follow-up visits (both sched-
uled and emergency if the patient developed new symp-
toms), careful maintenance of the ocular surface through
the use of preservative-free lubricants, judicious use of
topical steroids, and appropriate use of tarsorrhaphy con-
tribute to successful PK in VZV. In our study, one pa-
tient who developed recurrent neurotrophic ulceration
declined tarsorrhaphy and ultimately had cicatrization of
his graft. The second failure occurred as a result of a
compromised tarsorrhaphy in a severely neurotrophic
eye. Reed et al. (15) and Marsh and Cooper (14) also
emphasized the importance of tarsorrhaphy in their
cases. We hypothesize that severely neurotrophic eyes
are at higher risk of graft failure, and that objective pre-
operative assessment of corneal sensation may assist in
the selection of patients for successful transplantation.
Perhaps this is the reason for a higher success rate in our
patients with varicella. Further study in this area may be
helpful. Early and effective treatment of graft rejection is
dependent on educating the patients about the early signs
and symptoms of rejection.
Traditionally, ophthalmologists have reserved surgical
intervention in eyes with corneal involvement from VZV
for only the most severe cases. The results of this study,
together with previous reports, suggest that effective vi-
sual rehabilitation can be achieved after PK in VZV pa-
tients. Careful postoperative management can result in
good functional visual acuity when PK is performed in
eyes with VZV keratopathy.
Acknowledgment: This study was supported in part by a
grant from the Conselho Nacional de Desenvolvimento Cien-
tifico e Tecnologico (CNPq), Brazil (Dr. Marco A. G. Tanure).
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