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Primary orbital melanoma in association

with cellular blue nevus


Digital Journal of Ophthalmology 2014
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Volume 20, Number 3
July 14, 2014
DOI: 10.5693/djo.01.2014.02.001

Tarek El-Sawy , MD, PhD | Orbital Oncology Ophthalmic Plastic Surgery Program,
Department of Plastic Surgery, The University of Texas MD Anderson Cancer
Center, Houston, Texas
Mathieu F. Bakhoum, PhD | Orbital Oncology & Ophthalmic Plastic Surgery
Program, Department of Plastic Surgery, The University of Texas MD Anderson
Cancer Center, Houston, Texas
Michael Tetzlaff, MD, PhD | Department of Pathology, The University of Texas MD
Anderson Cancer Center, Houston, Texas
Qasiem J. Nasser, MD | Orbital Oncology Ophthalmic Plastic Surgery Program,
Department of Plastic Surgery, The University of Texas MD Anderson Cancer
Center, Houston, Texas
Victor G. Prieto, MD, PhD | Department of Pathology, The University of Texas MD
Anderson Cancer Center, Houston, Texas
Doina Ivan, MD | Department of Pathology, The University of Texas MD Anderson
Cancer Center, Houston, Texas
Matthew C. Sniegowski, MD | Orbital Oncology Ophthalmic Plastic Surgery
Program, Department of Plastic Surgery, The University of Texas MD Anderson
Cancer Center, Houston, Texas
Vivian T. Yin, MD | Orbital Oncology Ophthalmic Plastic Surgery Program,
Department of Plastic Surgery, The University of Texas MD Anderson Cancer
Center, Houston, Texas
Caroline Pan, MD | Department of Ophthalmology, The University of Colorado
School of Medicine, Denver, Colorado
Vikram Durairaj, MD | Department of Ophthalmology, The University of Colorado
School of Medicine, Denver, Colorado
Bita Esmaeli, MD | Orbital Oncology & Ophthalmic Plastic Surgery Program,
Department of Plastic Surgery, The University of Texas MD Anderson Cancer
Center, Houston, Texas

ABSTRACT INTRODUCTION MATERIALS AND


METHODS RESULTS DISCUSSION ACKNOWLEDGEMENTS REFERENCES

Abstract
Purpose
To describe 3 cases of primary orbital melanoma associated with either known or
subsequently discovered cellular blue nevus.
Methods
The clinical records and surgical specimens of 3 patients who underwent orbital
exenteration for primary orbital melanoma and who had a cellular blue nevus
diagnosed before or after detection of the melanoma were retrospectively
reviewed.

Results
All 3 patients presented with signs and symptoms of an orbital mass. Subsequent
biopsy revealed invasive melanoma. One patient had a known history of
congenital cellular blue nevus of the eyelid from which the orbital melanoma
originated. The other 2 patients had no known history of cutaneous pigmentation
or blue nevus. In these 2 patients, the cellular blue nevus was detected on
pathologic review of the orbital exenteration specimen (1 patient) or surgical
biopsy specimen (1 patient). All 3 patients underwent total body positron
emission tomography/computed tomography, and in all 3 results were negative
for other sites of disease involvement. In the 2 patients without a previously
known nevus a total body skin check was negative for other primary melanoma
lesions. All 3 patients underwent orbital exenteration followed by postoperative
radiation therapy.

Conclusions
Thorough evaluation of biopsy specimens of primary orbital melanoma is
warranted to ensure identification of any associated blue nevus because blue nevi
are precursor lesions for orbital melanoma, and the presence of a blue nevus
would support a primary orbital melanoma rather than a metastatic lesion.
Patients with a known blue nevus of the periocular skin and ocular adnexa should
be monitored closely for signs of malignant transformation.
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Introduction
Primary orbital melanoma is exceedingly rare and estimated to account for fewer
than 1% of orbital tumors in most large series.(1,2) The vast majority of orbital
melanomas are either metastatic or represent extension from skin and
conjunctival melanomas.(3) Distinguishing primary orbital melanoma from
metastatic orbital melanoma or extension from adjacent structures is essential
because the treatment for primary melanoma of the orbit is usually orbital
exenteration, whereas exenteration would only be appropriate as a palliative
measure in cases of metastasis or extension from adjacent orbital structures.

Blue nevus and cellular blue nevus are benign, intradermal melanocytic tumors
that are believed to represent the arrest of neural crest melanocyte precursors
within the dermis. They differ in degree of cellularity. The presence of an
associated cellular blue nevus on pathologic examination of an orbital melanoma
provides evidence supporting a primary orbital melanoma because the cellular
blue nevus component is a precursor lesion.(4,5) We report 3 cases of primary
orbital melanoma associated with a cellular blue nevus.
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Materials and Methods


This study was exempt from institutional review board review because of lack of
aggregate data. The clinical records of 3 patients with primary orbital melanoma
who had a diagnosis of a cellular blue nevus either before or after detection of the
primary orbital melanoma were retrospectively reviewed. Parameters recorded
from each patients chart included age at the time of diagnosis, sex, results of
systemic imaging work-up, results of pathologic examination of the diagnostic
biopsy specimen, surgical treatment, results of pathologic examination of the final
surgical specimen, duration and dose of postoperative radiotherapy, length of
follow-up, and disease status at last appointment.
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Results
Patient 1
A previously healthy 9-year-old girl with a known history of blue nevus involving
her right lower eyelid and cheek since birth (Figure 1) presented to MD Anderson
Cancer Center, Houston, with progressive proptosis of the right eye and swelling
of the right lower eyelid. A surgical debulking procedure by her local oculoplastic
surgeon a few months earlier confirmed the presence of invasive melanoma in
the orbit. She was referred to MD Anderson for further management.

On examination at our center, visual acuity was 20/20, ocular motility was full,
without diplopia, and visual fields were full. Magnetic resonance imaging (MRI)
revealed an orbital mass with direct extension into the pterygopalatine fossa
along the inferior orbital fissure (Figure 2) and approaching the superior orbital
fissure. Systemic work-up included a total body positron emission tomography
(PET), computed tomography (CT) scan, ultrasonography of regional lymph
nodes, and chest radiography. All scans were negative for metastatic disease.

The patient underwent an orbital exenteration, partial maxillectomy, partial


ethmoidectomy, partial sphenoidectomy, and dissection of the deep orbital apical
and skull base extension of the lesion performed by a multidisciplinary surgical
team, including Oculoplastics, Head and Neck Surgery, and Neurosurgery.
Pathologic examination of the surgical specimen revealed several foci of invasive
melanoma associated with an atypical cellular blue nevus (Figure 3). There was
extensive cellular blue nevus within the orbit, conjunctiva, and skin. The margins
of the resection specimen were negative for melanoma. Immunochemical staining
for markers of melanocytic differentiation was performed. HMB-45 was diffusely
positive in the tumor cells (not shown). An anti-MART1/Ki-67 cocktail was used to
assess the proliferative index of the melanocytes comprising the lesion revealed
the tumor cells to be diffusely positive for MART-1 and further showed areas of
melanoma juxtaposed with atypical cellular blue nevus: the melanoma cells
exhibited an increased (Ki-67-positive) proliferation rate in comparison to the
lower proliferation rate of the nevus cells (not shown). The strong, diffuse
positivity for both HMB-45 and MART-1 throughout the lesion confirmed
melanocytic differentiation, and the elevated proliferation rate (measured by Ki-
67) in the atypical epithelioid cells (compared to the benign component)
supported the diagnosis of melanoma arising in association with a nevus. The
orbital defect was repaired with an anterolateral thigh free flap. The patient was
started on postoperative proton radiation therapy 6 weeks after orbital
exenteration and received a total dose of 60 Gy-equivalents delivered in 30
fractions. At the last follow-up, 36 months after orbital exenteration, she was
without evidence of disease.

Patient 2
A previously healthy 54-year-old woman presented to MD Anderson with
proptosis of the left eye and a mass in the left orbit on imaging (Figure 4). There
were no complaints of decreased visual acuity, diplopia, or pain. A biopsy of the
mass performed prior to referral to our center was reviewed and demonstrated
invasive melanoma strongly and diffusely positive for markers of melanocytic
differentiation, including Melan A and HMB-45 (Figure 5). The lesion lacked an
obvious connection to the epidermis, exhibited a well-circumscribed architecture,
and was comprised of a monotonous proliferation of epithelioid cellsfeatures
suggestive of metastasis. However, a total body skin examination and a total
body PET and CT scan were negative for tumor, and ultrasonography of the neck
did not demonstrate lymphadenopathy.

The lesion was assumed to be a primary orbital melanoma. An orbital


exenteration was performed, and the socket was reconstructed with a radial arm
free flap and an overlying skin graft. Final review of the orbital exenteration
specimen revealed invasive melanoma with perineural invasion arising in
association with a cellular blue nevus. The patient began postoperative intensity-
modulated radiation therapy approximately 5 weeks after surgery and received a
total dose of 60 Gy in 30 fractions. At last follow-up, 24 months after orbital
exenteration, the patient was doing well and was without evidence of disease.

Patient 3
A previously healthy 44-year-old woman presented to an outside institution with
intermittent right-sided visual disturbances of several months duration. At that
time, right optic disc edema was noted, and on subsequent orbital MRI, a small
lesion was identified that abutted the optic nerve (Figure 6). Biopsy of this lesion
revealed invasive melanoma. The patient was then referred to our institution.

Additional histopathologic evaluation of the surgical biopsy specimen at our


institution confirmed the presence of an invasive melanoma and revealed that it
arose in association with a cellular blue nevus (Figure 7). The tumor cells were
strongly and diffusely positive for Melan A, HMB-45, and tyrosinase and focally
positive for S-100 (data not shown). Further immunohistochemical staining with
anti-MART1/Ki67 demonstrated positive staining in the region of the tumor with a
very low proliferative rate, which confirmed the histologic impression of an
associated focus of cellular blue nevus.

A total body skin examination and total body PET-CT scan were negative for
tumor. An orbital exenteration followed by postoperative high-dose radiation
therapy was recommended, and this treatment was carried out at the patients
home institution. At last follow-up, 24 months after orbital exenteration, the
patient was without evidence of disease.
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Figure 1
External photograph of right periocular region of Patient 1
demonstrating blue discoloration of skin, conjunctiva, and
caruncle.

Figure 2
T1-weighted magnetic resonance imaging (MRI) of patient
1 demonstrating extensive disease (white arrow) within
the right orbit extending to the orbital apex and through
the inferior orbital fissure to the pterygopalatine fossa.

Figure 3
A, Histologic sections from resection specimen from
patient 1 reveal a monotonous proliferation of malignant
epithelioid cells forming a well-circumscribed nodule in
association with a blue nevus (outlined section indicates
the area magnified in part). B, Atypical cellular blue nevus
component is designated by the solid black arrow, while
the invasive melanoma forming an expansile nodule is
designated by the solid white arrow. Malignant epithelioid cells (solid white arrow)
juxtaposed with benign spindled blue nevus component (solid black arrow).

Figure 4
Computed tomography scan of patient 2 demonstrating a
mass in the left superior orbit infiltrating the superior
rectus muscle (black arrow).
Figure 5
Histologic sections of resection specimen from patient 2
revealing a monotonous proliferation of malignant
epithelioid cells forming a well-circumscribed nodule in
fibrovascular soft tissue (A). Immunohistochemical
studies demonstrate diffuse, strong positivity in the tumor
cells for markers of melanocytic differentiation, including
Melan-A (B), S100 (C), and HMB-45 (D). The combined
positivity for these markers confirms melanocytic differentiation by the tumor cells and,
together with the morphology, confirms the diagnosis of melanoma.

Figure 6
Axial T2-weighted MRI of patient 3 demonstrating a mass
medial to the optic nerve and just posterior to the globe
on the right side (white arrow).

Figure 7
A, Histologic sections of resection specimen from patient
3 reveal a proliferation of spindle and epithelioid cells
forming an expansile nodule in fibrovascular soft tissue
with tumor necrosis present in the area designated by the
asterisk; the dashed line designates the boundary
between viable and necrotic tumor. B, Perineural invasion
is designated by the solid white arrow. C, High-power
examination reveals proliferation of malignant epithelioid melanocytes forming an
expansile nodule (solid black arrow), which is juxtaposed with a proliferation of
cytologically benign spindled and dendritic melanocytes (designated by a solid white
arrow).

Discussion
We highlight the importance of careful evaluation of surgical biopsy specimens for
detection of associated cellular blue nevus in patients with primary orbital
melanoma. The finding of a cellular blue nevus supports the diagnosis of a
primary orbital melanoma rather than a metastatic lesion. The identification of a
cellular blue nevus component in the orbital specimen together with a negative
systemic work-up, which should include at least a total body PET-CT scan and a
total body skin check, gives high likelihood for the diagnosis of a primary rather
than a metastatic orbital melanoma.
The histologic diagnosis of a blue nevus or a cellular blue nevus can be difficult
because of the relative rarity of these lesions. In addition, whereas the invasive
melanoma component may involve a large component of the orbital mass, the
blue nevus component may represent a small part of the surgical biopsy
specimen and could be overlooked. The correct diagnosis may also depend on the
experience of the pathologist.

The case of patient 1 highlights the possibility of malignant transformation and


the importance of surveillance in patients with congenital blue nevus involving the
periocular skin. This type of transformation has previously been described in the
ophthalmic literature.(4) In a patient with congenital blue nevus, any changes in
size or appearance of the nevus and any onset of proptosis or displacement of the
globe should prompt a biopsy of the involved area to rule out transformation to
invasive melanoma.

Orbital melanoma usually metastasizes hematogenously, unlike eyelid or


conjunctival melanoma, which metastasizes via the draining lymph nodes. This
metastatic behavior of orbital melanoma is presumed to be due to the lack of
lymphatics in the orbit. After treatment of a primary orbital melanoma in a
patient with blue nevus follow-up surveillance might include total body PET-CT
scans and careful clinical examinations.
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Acknowledgements
Supported in part by the National Cancer Institute under award number
P30CA016672.

Presented at the Fall 2011 meeting of the ASOPRS, Orlando, Florida.


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References
1. Shields CL, Shields JA. Ocular melanoma: relatively rare but requiring respect.
Clin Dermatol 2009;27:122-33.
2. Tellado M, Specht CS, McLean IW, Grossniklaus HE, Zimmerman LE. Primary
orbital melanomas. Ophthalmology 1996;103:929-32.
3. Polito E, Leccisotti A. Primary and secondary orbital melanomas: a clinical and
prognostic study. Ophthal Plast Reconstr Surg 1995;11:169-81.
4. Gndz K, Shields JA, Shields CL, Eagle RC Jr. Periorbital cellular blue nevus
leading to orbitopalpebral and intracranial melanoma. Ophthalmology
1998;105:2046-50.
5. Rice CD, Brown HH. Primary orbital melanoma associated with orbital
melanocytosis. Arch Ophthalmol 1990;108:1130-4.
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Copyright 2015. All rights reserved. Reproduction in whole or in part in any form or
medium without expressed written permission of the Digital Journal of Ophthalmology is
prohibited.
High myopia as a risk factor for post-
LASIK ectasia: A case report
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Digital Journal of Ophthalmology 2009
Volume 15, Number 1
February 23, 2009

Mona Harissi-Dagher, MD | Massachusetts Eye and Ear Infirmary, Boston, MA,


USA and Department of Ophthalmology, Universite de Montreal, Quebec, Canada
Sonja A.F. Frimmel | Friedrich-Alexander-University Erlangen-Nuremberg,
Germany
Samir Melki, MD, PhD | Massachusetts Eye and Ear Infirmary, Boston, MA and
Boston Eye Group, Boston, MA, USA

ABSTRACT INTRODUCTION MATERIALS AND


METHODS RESULTS DISCUSSION ACKNOWLEDGEMENTS REFERENCES

Abstract

Purpose: To describe the case of a patient developing corneal ectasia following


LASIK for the correction of myopic astigmatism.

Materials and Methods: A 39-year-old man underwent bilateral uneventful


LASIK for myopic astigmatism of -10.25 -1.75 x040 OD and -8.00 -2.50 x005 OS.
Preoperative corneal pachymetry was 542 micrometers OD and 543 micrometers
OS. Preoperative corneal topography showed bilateral oblique bow-tie patterns.
Central keratometry measurements were 45.12 D @ 124 / 43.87 D @ 34 OD and
44.87 D @ 78 / 43.12 D @ 168 OS. Keratoconus or forme fruste keratoconus
were not present preoperatively.

Results: The residual stromal bed was 314 micrometers OD and 295
micrometers OS. Increasing astigmatism was documented progressively after
LASIK. Central keratometry and topography were performed with evidence of
ectasia OD at 17 months post-operatively and early evidence of ectasia OS at last
follow-up of 58 months.

Conclusion: High myopia appears to be a predisposing factor in this patient.


High myopia may need to be considered as an ectasia risk factor independent of
amount of ablation or residual stromal bed thickness and in the absence of forme
fruste keratoconus. The possibility remains that ectasia was due to an
unidentified risk factor or an intrinsic corneal problem with this patient's right
eye.

Keywords: LASIK, Ectasia, Forme Fruste Keratoconus, Myopia

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Introduction

Laser in situ keratomileusis (LASIK) is currently the most common refractive


surgical procedure for the treatment of myopia. Its safety, effectiveness, and
success have been widely reported.(1) With an increasing number of LASIK
surgeries performed and with longer follow-ups, more complications are being
observed. The incidence of serious complications is relatively low, but visual
consequences can be dramatic considering the elective nature of this
procedure.(1) Ectasia resulting from an unknown alteration in the biomechanical
strength can lead to loss of best-corrected visual acuity and the need for a
corneal transplant in severe cases. Seiler et al.described the first three cases of
corneal ectasia after LASIK in 1998;(2) more cases have been reported since
then. Herein, we describe a case of post-LASIK ectasia with high myopia as the
identifiable risk factor.

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Materials and Methods

Case report
A 39-year-old man of middle-eastern descent underwent refractive surgery for
the correction of myopic astigmatism. Past ocular history was unremarkable.
There was no history of contact lens wear. His uncorrected visual acuity (UCVA)
was count fingers in both eyes. Best spectacle-corrected visual acuity (BSCVA)
was 20/40 in both eyes with a refraction of 10.25 1.75 x040 in the right eye
(OD) and 8.00 2.50 x005 in the left eye (OS). After instillation of Tropicamide
1% and Cyclopentolate 0.5%, the visual acuity (VA) was 20/30 OD and 20/25 OS
with a refraction of 10.25 1.50 x040 OD and 7.75 3.25 x005 OS. Three
measurements of corneal pachymetry were taken with Sonogage Pachymeter
(Corneo-Gage Plus Cleveland, OH, USA), and the lowest measurement was
recorded. Preoperative corneal pachymetry was 542 micrometers OD and 543
micrometers OS. Preoperative Humphrey Atlas Corneal Topography Systems
(version A11.2, Carl Zeiss Inc.) showed bilateral oblique bow-tie patterns (Figure
1). No other topographers were available and hence posterior float and anterior
float were not obtained. Central keratometry measurements were 45.12 D @ 124
/ 43.87 D @ 34 OD and 44.87 D @ 78 / 43.12 D @ 168 OS.

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Figure 1
Pre-operative corneal topography OD and OS showing
bilateral oblique bow-tie patterns. A standard 0.5 D
interval scale is used.

Results

On June 21, 2002, uneventful LASIK was performed OS first followed by OD


seven days later on June 28, 2002. There were no intraoperative complications.
Excimer laser ablation was performed with a VISX Star S3 IR Excimer Laser
System (VISX Technology, California) after a superiorly hinged flap was made
with a Hansatome microkeratome (Bausch & Lomb, Rochester, NY) using a 9.5-
mm suction ring. A 160 micron Hansatome head was used being that it provided
the thinnest available cut at the time of surgery. Intraoperative pachymetry was
performed after lifting the flap, taking 3 central measurements, and recording the
lowest. The residual stromal bed was calculated by obtaining the lowest central
pachymetry and deriving the ablation depth from the laser. In this patient, the
targeted flap thickness of 160 micrometers resulted in a measured flap thickness
of 124 micrometers OD and 153 micrometers OS, thinner than the corresponding
settings on the microkeratome. Hence, the calculated residual stromal bed was
314 micrometers OD and 295 micrometers OS after an ablation of 103
micrometers OD and 95 micrometers OS. Laser ablation OD was performed with
an M Ellipse (6.0 mm x 5.4 mm diameter, 80 micrometers depth) and an M
Sphere (5.5 mm diameter, 23 micrometers depth). For OS, laser ablation was
performed with an M Elllipse (6.5 mm x 5.3 mm diameter, 95 micrometers
depth).

The patient achieved his best level of UCVA in the early post-operative period.
UCVA was 20/40 OD eight days after LASIK and 20/50 OS two weeks after
LASIK. BSCVA was 20/20 OD with 1.00-1.00x020 and 20/30 OS with -1.25-
1.00x125 two weeks after the initial procedure OS.

Five months after LASIK, the UCVA decreased to 20/70 in both eyes. At that time
the patient complained of blurred vision at distance and difficulty driving at night.
No evidence of ectatic topography was found. The patient was followed and
monitored for visual stability while entertaining the possibility of performing an
enhancement.

The first evidence of ectasia was noted OD in September 2003, 17 months after
the initial procedure. At that time, BSCVA was 20/40 OD with a manifest
refraction of -6.50-4.00x060 and 20/30 OS with a manifest refraction of -1.50
1.25 x122. His axial videokeratography map OD revealed an asymmetric bow-tie
pattern with inferior steepening. The latter was also seen on the tangential map
(Figure 2). In the second to third year after LASIK, the refractive error stabilized
with BSCVA of 20/150 OD and 20/30 OS with 3.50 3.25 x070 and 0.75 -3.75
x120, respectively, indicating progressing ectasia OU. At the end of the third
year, corneal topography showed central to inferior steepening OD typical of
ectasia and normal topography OS. At last follow-up of 58 months, BSCVA was
20/200 OD and 20/25 OS with -3.00 -4.50 x075 and -5.25 3.75 x135,
respectively. Central keratometry measured 52.37 D@ 132 / 50.50 D@42 OD and
44.25 D @38 / 39.50 D @128 OS (Table 1). Pachymetry was 463 micrometers
OD and 471 micrometers OS.

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Figure 2
Corneal topography demonstrating severe inferior
steepening OD and asymmetric bow tie OS with inferior
steepening 58 months post-operatively. A standard 0.5 D
interval scale is used.
Table 1
Keratometric Readings Pre-op and Post-LASIK OU.

Discussion

Corneal ectasia is a known complication of LASIK that can lead to devastating


visual consequences. It is defined as an acquired, non-inflammatory,
biomechanical outward bulging of the cornea. It results in progressive thinning
and central to inferior steepening of the cornea. This usually happens in the
context of a myopic shift in refraction, increasing regular astigmatism, irregular
astigmatism, and eventually loss of BCVA.

Proper preoperative evaluation and patient selection are essential to decrease the
risk of ectasia. Certain preoperative risk factors for ectasia have been
determined. These include high myopia,(2-9) high astigmatism, reduced
preoperative corneal thickness, and low residual stromal bed. These have been
reported in the majority of ectasia cases, but none of these characteristics alone
definitively predicts the development of ectasia. In fact, ectasia can develop in
eyes with low myopia and no currently identifiable risk factors.(10)

Documented diagnoses predisposing to corneal ectasia after excimer laser


ablation are keratoconus, keratoconus suspect, or pellucid marginal degeneration.
None of these conditions was present at the time of LASIK either by exam or by
corneal topography. Our patient was 39 years old at the time of the surgery with
a history of a stable refraction making the diagnosis of labile keratoconus
extremely unlikely. LASIK retreatment may increase the risk of ectasia as it
ablates more corneal tissue and thins the cornea further.

Ectasia developed in our patient without the presence of any of the three main
predisposing factors: keratoconus or forme fruste keratoconus, LASIK
retreatment or a thin residual bed. Although the patient has oblique and slightly
asymmetric astigmatism, it does not meet the criteria for a keratoconus-suspect.
The patients vision was not correctable to 20/20, but instead his BCVA was
20/40 OU. In retrospect, this may be an indication of forme fruste keratoconus;
nevertheless, it is not unusual for high myopes not to correct to 20/20 vision as
demonstrated by laser interference fringes.(11) The lack of anterior and posterior
float does not allow us to rule out forme fruste keratoconus either, but imaging of
the posterior surface was not a widespread modality at the time the patient was
evaluated for LASIK. In summary, myopia seems to be the only identifiable
factor, and this has already been reported as a risk factor for post-LASIK ectasia.
This is not a new clinical finding, but rather a possible confirmatory case of the
existing literature on the subject. It is not clear from previous reports (4) whether
high myopia predisposes to ectasia because of the larger amount of tissue
ablation or from other inherent factors.

In fact, risk factors related to preoperative and postoperative corneal thickness


were not present in this case. Preoperative central corneal thickness was 542
micrometers OD and 543 micrometers OS, higher than the advocated 500
micrometers limit for LASIK.(10) Machat suggested a posterior stromal thickness
of no less than 50 percent of the corneal thickness.(12) In our patient, posterior
stromal thickness with respect to total corneal thickness was measured at 57.9
percent OD and 54.3 percent OS.

A residual stromal bed thickness of 250 micrometers has been advocated as a


relatively safe limit for the prevention of corneal ectasia.(2,3) It appears that the
forward shift of the cornea may be more marked with less than 250 micrometers.
This is not a strong relationship however, and one should conclude from the
literature that the 250 micrometers limit is not necessarily safe.

Unknowingly cutting thicker flaps may result in thinner residual stromal bed
thickness than intended leading to ectasia erroneously attributed to other risk
factors. Also, the thickness of the corneal flap may vary with the same
microkeratome in the same surgeons hands.(13,14) The achieved flap in one
reported case of ectasia was excessively thick leading to ectasia immediately
after surgery despite avoidance of laser ablation.(15) In many other ectasia case
reports, the corneal flap was much thicker than planned.(16) Other case reports
lack intraoperative pachymetry measurements leaving a question around this
important variable.(4) We advocate routinely measuring the intraoperative bed
thickness to ensure adequate room for the laser ablation. In our patient, the
targeted flap thickness of 160 micrometers resulted in a measured flap thickness
of 124 micrometers OD and 153 micrometers OS, thinner than the corresponding
settings on the microkeratome.

The residual stromal bed thickness is also directly related to the amount of
corneal tissue removed. To minimize tissue removal, surgery on this patient was
performed with a combined ablation zone diameter of 5.5/6 mm OD and 6.5 mm
OS. Based on the Munnerlyns formula,(17) as the width of ablation increases,
the thickness of the residual stromal bed decreases proportionately; thus, the risk
of developing ectasia increases with wider ablations. In OD, 2 diopters were
treated at a zone of 5.5 mm diameter thereby further minimizing tissue removal.
This brought the amount of tissue removal OD (103 micrometers) quite close to
OS (95 micrometers). The reduced laser ablation, in combination with a thinner
corneal flap, resulted in a thicker residual stromal bed thickness in the ectatic OD
(314 micrometers) compared to OS (295 micrometers).

It is possible that a safe residual stromal bed thickness is patient-dependent


relative to other biomechanical properties of the cornea. It has been postulated
that the posterior corneal stroma has less biomechanical strength than the
anterior layers.(18) Lee et al. reported on the biomechanics of the cornea noting
that there were no statistically significant changes in the post-surgical forward
shift of the posterior corneal surface if the residual corneal thickness is more than
350 micrometers or if the ablation ratio per total cornea is less than 10
percent.(12) In our case, the ablation ratio was not significantly different
between the two eyes. The measured ablation was 103 micrometers OD and 95
micrometers OS representing 19.2 percent OD and 17.5 percent OS ablation ratio
per total cornea. These two figures are higher than the advocated 10 percent but
are essentially similar in both eyes. Yet, OD suffered earlier and more severe
ectatic changes than OS. In this case report, myopia is the only identifiable risk
factor, but the possibility remains that ectasia was due to an unidentified risk
factor or an intrinsic corneal problem with this patient's right eye.

Conclusion
In summary, post-LASIK ectasia OD was noted unilaterally initially even though
other known intraoperative predisposing factors would have predicted a slightly
higher ectasia risk for OS. The only predisposing factor OD was the higher level of
preoperative myopia. It is possible that higher levels of myopia may be
associated with different corneal biomechanical properties that predispose to
ectasia. These inherent factors as well as a safe level of myopia remain to be
elucidated in future studies.

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Acknowledgements

Financial support: none


Proprietary interest: none

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References

1. Sugar A, Rapuano CJ, Culbertson WW, Huang D, Varley GA, Agapitos PJ, de
Luise VP, Koch DD. Laser in situ keratomileusis for myopia and astigmatism:
Safety and efficacy: A report by the American academy of
ophthalmology. Ophthalmology. 2002; 109:175-187.
2. Seiler T, Koufala K, Richter G. Iatrogenic keratectasia after laser in situ
keratomileusis. J Refract Surg. 1998;14:312-317.
3. Joo C, Kim T. Corneal ectasia detected after laser in situ keratomileusis for
correction less than 12 diopters of myopia. J Cataract Refract
Surg. 2002;26:292-295.
4. Randleman JB, Russell B, Ward MA, Thompson KP, Stulting RD. Risk factors
and prognosis for corneal ectasia after LASIK. Ophthalmology. 2003;110:267-
275.
5. Tabbara KF, Kotb AA. Risk factors for corneal ectasia after
LASIK. Ophthalmology.2006;113(9):1618-22.
6. Condon PI, O'Keefe M, Binder PS. Long-term results of laser in situ
keratomileusis for high myopia: risk for ectasia. J Cataract Refract
Surg. 2007;33(4):583-90.
7. Randleman JB, Woodward M, Lynn MJ, Stulting RD. Risk assessment for
ectasia after corneal refractive surgery. Ophthalmology. 2008;115(1):37-50.
Epub 2007 Jul 12.
8. Binder PS. Analysis of ectasia after laser in situ keratomileusis: risk factors. J
Cataract Refract Surg. 2007;33(9):1530-8.
9. Caster AI, Friess DW, Potvin RJ. Absence of keratectasia after LASIK in eyes
with preoperative central corneal thickness of 450 to 500 microns. J Refract
Surg. 2007;23(8):782-8.
10. Amoils SP, Deist MB, Gous P, Amoils PM. Iatrogenic keratectasia after laser in
situ keratomileusis for less than 4.0 to 7.0 diopters of myopia. J Cataract Refract
Surg. 2000;26:967-977.
11. Coletta NJ, Watson T. Effect of myopia on visual acuity measured with laser
interference fringes. Vision Res. 2006;46(5):636-51
12. Machat JJ. Eximer laser refractive surgery; practice and principles. Thorofare,
NJ, Slack Inc, 1996;300.
13. Lee DH, Seo S, Jeong KW, Shin AC, Vukich JA. Early spatial changes in the
posterior corneal surface after laser in situ keratomileusis. J Cataract Refract
Surg. 2003;29:778-784.
14. Flanagan GF, Binder PS. The precision of flap measurements for laser in situ
keratomileusis in 4428 eyes. J Refractive Surg. 2003;19:113-123
15. Haw WW, Manche EE. Iatrogenic keratectasia after a deep primary
keratotomy during laser in situ keratomileusis. Am J Ophthalmol. 2001;132:920-
921.
16. Tervo TM. Iatrogenic keratectasia after laser in situ keratomileusis [letter]. J
Cataract Refract Surg. 2001;27:490-491.
17. Gatinel D, Hoang-Xuan T, Azar DT. Determination of corneal asphericity after
myopia surgery with the excimer laser: a mathematical model. Invest Ophthalmol
Vis Sci. 2001;42(8):1736-42.
18. Andreassen TT, Simonsen AH, Oxlund H. Biomechanical properties of
keratoconus and normal corneas. Exp Eye Res. 1980;31:435-441.

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Copyright 2015. All rights reserved. Reproduction in whole or in part in any form or
medium without expressed written permission of the Digital Journal of Ophthalmology is
prohibited.
The Effect of Lubricating Eye Drops on
Optical Coherence Tomography Imaging
of the Retina
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Digital Journal of Ophthalmology 2009


Volume 15, Number 2
May 30, 2009

Nicola G. Ghazi, MD | University of Virginia


Jason W. Much, MD | University of Virginia

ABSTRACT INTRODUCTION MATERIALS AND


METHODS RESULTS DISCUSSION REFERENCES

Abstract

Introduction: The goal of this study was to examine the potential value of
corneal lubrication in improving the quality of optical coherence tomography
(OCT) imaging of the retina.

Materials and Methods: This study is a consecutive series of 13 eyes of 11


patients in whom repeated attempts at OCT imaging failed to yield a good quality
study despite the absence of significant media opacity or inadequate pupil
dilation. Immediately following several poor quality scans, each eye received
lubricating eye drops. The quality of images before and after the administration of
drops was assessed.

Results: A statistically significant improvement in OCT image quality was


observed following the administration of eye drops in each case. The change in
mean signal strength (SS) was from 4.35 to 6.26 (p= 0.0002). The proportion of
scans with erroneous edge detection decreased from 41 to 13 percent.

Discussion: Lubricating drops appear to improve the quality and feasibility of


OCT imaging in selected cases.

Key Words: Corneal dryness, lubricating eye drops, optical coherence


tomography, OCT.

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Introduction

Optical coherence tomography (OCT) imaging has revolutionized the practice of


ophthalmology especially in the fields of glaucoma and retina. However, poor
image quality can lead to unreliable quantitative data, misdiagnosis, difficulty
with treatment decisions, and inability to follow the course of disease due to
limitations in reproducibility. OCT image quality has been shown to be adversely
affected by corneal drying.(1) Lubricating eye drops would be a simple and
inexpensive way to enhance image quality and reproducibility in selected
patients.

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Materials and Methods

Approval for this study was obtained from the Institutional Review Board at the
University of Virginia. This study is a consecutive series of 13 eyes of 11 patients
in whom repeated attempts at OCT imaging failed to yield a good quality study
despite the absence of significant media opacity or inadequate pupil dilation. All
scans were performed by a trained technician on the same OCT machine (OCT
Stratus, Third Generation, Model 3000, software 4.0, Carl Zeiss Ophthalmic
Systems, Dublin, CA, USA). For the purpose of this study, an OCT study was
considered of good quality if at least four of six (for fast macular imaging) or two
of three (for nerve fiber layer imaging) scans had correct edge detection and a
signal strength of greater than 6.0. Correct edge detection refers to the correct
identification of the inner and outer retinal or retinal nerve fiber layer boundaries
by the OCT software thus allowing accurate thickness measurements. Signal
strength is the proprietary OCT software parameter for image quality based on
signal-to-noise ratio and the uniformity of the signal across a scan.(2)
Immediately following 1 to 4 poor quality scans, each eye received a single
lubricating eye drop (Systane lubricant eye drops, Alcon) just before reattempting
image acquisition using the same OCT parameters.

The quality of images before and after the administration of eye drops was
assessed. Data recorded included retinal nerve fiber layer (RNFL) thickness,
macular thickness measurements, signal strength (SS), and the number of scans
with failed edge detection. Statistical analysis was performed using paired and
unpaired t-tests.

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Results

Patient demographics, ocular diagnoses and imaging details are listed in the
Table. Of the 11 patients, 6 were male, 5 were female, and the mean age was 61
years. One patient carried a diagnosis of dry eye syndrome, one patient had
blepharitis and was noted to have punctate epithelial erosions the day of the
scan, and another patient had map-dot-fingerprint corneal dystrophy. The other
patients had no documented tear film or corneal abnormalities that would place
them at risk for surface irregularity.

A statistically significant improvement in OCT image quality was observed


following the administration of eye drops in each case. In all but one eye, this
was possible on the first attempt following application of the lubricating drops.
The change in mean signal strength (SS) was from 4.35 to 6.26 dB (p= 0.0002)
(Figure 1). The proportion of studies with an average SS greater than 6 increased
from 1.1 percent before to 67 percent after eye drop application. Statistical
significance was maintained even when the scan with the best SS prior to eye
drop application was chosen for comparison. Six of 13 eyes had scans with
correct edge detection before drops despite poor signal strength. After drops, 12
of 13 eyes had scans with proper edge detection. The proportion of scans with
erroneous edge detection decreased from 41 to 13 percent (Figure 2A and 2B). In
the 7 eyes with edge detection error before drops, the average retinal nerve fiber
layer thickness in focal sectors (1/12 pie on the OCT report) affected by the error
was 12.4 micrometers. Following eye drop application and restoration of correct
edge detection, the average thickness in these areas increased to 48.25
micrometers (p=0.00004).

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Table
Patient demographics and results.

Figure 1
Change in mean optical coherence tomography signal
strength (SS) before and after lubricating eye drops. The
SS significantly increased in every case following the
application of drops.

Figure 2
Edge detection before (A) and after (B) lubricating eye
drops in the same eye undergoing optical coherence
tomography for retinal nerve fiber layer (RNFL) imaging.
Note image degradation with reduction in reflectivity of
the RNFL with associated failure of edge detection and
collapse of the border detection lines (A). Following
application of a single drop of artificial tears during the same imaging session,
improvement in signal strength and image quality (B) with associated proper edge
detection was noted at the first attempt at re-imaging.

Discussion

Image quality is essential for the accurate interpretation of OCT test results.
Several studies have analyzed error and reproducibility of OCT measurements,(3-
6) but few have investigated the role of the tear film. Because OCT is a light-
based imaging system, image quality may be degraded secondary to the
scattering of light by the rough surface of a dry cornea. Stein et al. used eyelid
taping to demonstrate the effect of corneal drying on OCT image quality.(1) They
found a significant deterioration of image quality following induced corneal
exposure with lid taping; furthermore, image quality slowly recovered after
patients were allowed to blink.
The patients in our study demonstrated persistently decreased image quality
even in the absence of significant media opacity or poor pupillary dilatation.
Lubricating eye drops improved scan quality immediately after the drops were
applied. This is most likely due to the restoration of a smooth optical corneal
surface following drop application. Following application of eye drops, the
proportion of scans with erroneous edge detection placement decreased from 41
to 13 percent (Figure 2A and 2B). We believe this to be related to the associated
improvement in SS. When the SS is poor (Figure 2A), the OCT cross sectional
image may be degraded so that the retinal or retinal nerve fiber layer boundaries
may not be distinct enough for proper edge detection, leading to collapse of the
border detection lines (Figure 2) with subsequent decreased thickness
measurements and poor reproducibility of imaging studies.(1) Restoration of
proper edge detection can explain the statistically significant increase in focal
thickness measurements observed following drop application in some of our
patients.

The major limitations of our study include the lack of a control group and the
small sample size. Our study also had a high proportion of patients with thyroid
eye disease, most of whom received nerve fiber layer scans for suspected optic
neuropathy. Such eyes are predisposed to dry eyes, and in future studies, we
plan to analyze data regarding objective measures of dry eyes in these patients
such as Schirmers testing and tear break-up time. Another limitation in our study
is that we did not systematically measure pupil size at the time of imaging;
however, all eyes were clinically judged to be well-dilated. Moreover, the
significant improvement in image quality following drop application makes pupil
size an unlikely confounder.

This small series suggests that lubricating drops appear to improve the quality
and feasibility of OCT imaging in selected cases. Eyes with poor quality OCT
imaging of the fundus with no apparent cause may benefit from the
administration of lubricating drops just before image acquisition even in the
absence of dry eye syndrome. We currently keep a bottle of artificial tears
available on the OCT machine table for potential use in such cases.

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References
1. Stein DM, Wollstein G, Ishikawa H, et al. Effect of corneal drying on optical
coherence tomography. Ophthalmology 2006; 113:985-91.
2. Stein DM, Ishikawa H, Hariprasad R, et al. A new quality assessment
parameter for optical coherence tomography. Br J Ophthalmol 2006; 90:186-90.
3. Olmedo M, Cadarso-Suarez C, Gomez-Ulla F, et al. Reproducibility of optic
nerve head measurements obtained by optical coherence tomography. Eur J
Ophthalmol 2005; 15:486-92.
4. Polito A, Del Borrello M, Isola M, et al. Repeatability and reproducibility of fast
macular thickness mapping with stratus optical coherence tomography. Arch
Ophthalmol 2005; 123:1330-7.
5. Ray R, Stinnett SS, Jaffe GJ. Evaluation of image artifact produced by optical
coherence tomography of retinal pathology. Am J Ophthalmol 2005; 139;18-29.
6. Sadda SR, Wu Z, Walsh AC, et al. Errors in retinal thickness measurements
obtained by optical coherence tomography. Ophthalmology 2006; 113:285-93.

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Copyright 2015. All rights reserved. Reproduction in whole or in part in any form or
medium without expressed written permission of the Digital Journal of Ophthalmology is
prohibited.
Prevalence and Risk Factors of Diabetic
Retinopathy among Jordanian Patients
with Type 2 Diabetes
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Digital Journal of Ophthalmology 2008


Volume 14, Number 2
August 4, 2008

Rasmieh M. Al-Amer | University of Jordan


Yousef Khader | Jordan University of Science and Technology
Samer Malas | Jordan University Hospital
Nakhleh Abu-Yaghi | Jordan University Hospital
Muawyah Al-Bdour | Jordan University Hospital
Kamel Ajlouni | National Center for Diabetes, Endocrinology and Genetics

ABSTRACT INTRODUCTION MATERIALS AND


METHODS RESULTS DISCUSSION ACKNOWLEDGEMENTS REFERENCES

Abstract

Objective
To estimate the prevalence of diabetic retinopathy among patients with type 2
diabetes mellitus (DM) who attended the National Center of Diabetes,
Endocrinology and Genetics (NCDEG) in Jordan, and to determine the relationship
between duration of DM, hyperglycemia, smoking, hypertension, age, gender,
body mass index (BMI) and diabetic retinopathy.

Methods
This is a cross-sectional study that investigates a sample of 1000 diabetic
patients suffering from type 2 DM who attended the NCDEG between September
2006 and January 2007. Eye examination by an ophthalmologist under adequate
dilatation was performed in all patients. Socio-demographic, clinical and
laboratory data were obtained. Diabetic Retinopathy was defined according to the
International Clinical Diabetic Retinopathy Severity Scale adopted by American
Academy of Ophthalmology (AAO) and the International Council of
Ophthalmology (ICO). Statistical analysis was carried out using the Statistical
Package for Social Sciences (SPSS, version 11.5).
Results
Out of 1000 patients; 51 percent were male, 49 percent were female. The mean
age and duration of diabetes were 57.8 and 9.6 years, respectively. The
prevalence of diabetic retinopathy in patients was 34.1 percent. Non-proliferative
diabetic retinopathy was documented in 24.5 percent, while 9.6 percent had
proliferative diabetic retinopathy. Duration of DM and hyperglycemia, as
measured by HbA1C, were statistically significantly associated with diabetic
retinopathy.

Conclusion
Diabetic retinopathy is highly prevalent among Jordanian patients with type 2
DM. Serious national efforts should be directed towards increasing primary
prevention through regular ophthalmic examinations and strict glycemic control in
patients with type 2 DM.

Keywords
Diabetes mellitus, Proliferative diabetic retinopathy, Non-proliferative diabetic
retinopathy, Hyperglycemia.

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Introduction

Diabetes Mellitus (DM) is considered to be a major health problem that is


predicted to turn into a global epidemic. The adult prevalence of DM in developed
countries is about 5 percent.(1) The actual number may be twice as high
considering all the cases which have not yet been diagnosed.(2) The prevalence
of diabetes in developing countries, such as the Arab countries, varies from 3 to
35 percent.(3) In a recent study in Jordan, the age-standardized prevalence of
DM and impaired fasting glucose tolerance were 17.1 percent and 7.8 percent
respectively, confirming that the prevalence of DM in Jordan is high and
increasing.(4)

Diabetic patients are prone to develop diabetic retinopathy (DR). During the first
two decades of the disease, nearly all patients with type 1 diabetes and 60
percent of those with type 2 diabetes develop retinopathy.(5) Blindness due to
diabetes is becoming an ever greater problem in developing countries.(6) In a
hospital based study from Jordan, DR was the leading cause of blindness (7).
Another study indicated that the prevalence of DR among type 2 diabetics was 50
percent (8), while a more recent study in 2005 reported that the overall
prevalence of DR among Jordanian diabetics was 64.1 percent (9).

The present study was conducted at the National Center for Diabetes
Endocrinology and Genetics (NCDEG) to estimate the prevalence of DR among
patients with type 2 DM and to describe the stages of DR among the study group.
The second aim of the study was to determine if there is any correlation between
DR and a number of independent variables including duration of DM,
hyperglycemia as measured by HbA1C level, smoking, hypertension, age, gender
and body mass index.

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Materials and Methods

A cross-sectional study format was adopted. It included 1000 patients with type 2
DM who attended the diabetic clinic at NCDEG located in Amman, Jordan between
September 2006 and January 2007. The study sample was selected randomly.
Pregnant women were excluded. The sample size was sufficient to provide 95
percent assurance that the margin of error in estimating the prevalence of DR
would not exceed 3 percent, assuming the most conservative estimate of
prevalence is 50 percent.

All patients underwent detailed eye examination by an ophthalmologist utilizing


slit-lamp biomicroscopy including fundus examination under adequate pupillary
dilatation with tropicamide 1 percent. Phenylephrine 10 percent was used in
patients who did not dilate with tropicamide. For the sake of staging DR, we
considered the eye with the most advanced stage. Data obtained included:
duration of DM, HbA1C level, smoking, hypertension, age, gender, body mass
index, and ophthalmic examination findings.

Ethical Considerations
The study was approved by the NCDEG ethics committee. Informed consent was
obtained from all patients included in the study.
Definition of variables
Diabetic retinopathy (DR)
The international clinical diabetic retinopathy severity scale adopted by the
American Academy of Ophthalmology (AAO) (10) and the International Council of
Ophthalmology (ICO) (11) were used to classify patients into non-proliferative
diabetic retinopathy (NPDR) versus proliferative diabetic retinopathy (PDR).

NPDR was subdivided into:


i. Mild NPDR: micro-aneurysms only;
ii. Moderate NPDR: more than just microaneurysms but less than severe;
iii. Severe NPDR: consisting of any of the following intra-retinal hemorrhage in
each of the four quadrants, venous beading in two or more quadrants, or
intraretinal microvascular abnormalities (IRMAs) in one or more quadrants AND
no signs of proliferative retinopathy.

PDR was defined as neovascularization at the optic disc (NVD) or elsewhere


(NVE).

Diabetic macular edema (DME) was present when any retinal thickening or hard
exudates were present in the macula.

Duration of DM
Duration of DM was defined as the time period between the age at diagnosis and
the time of examination. They were categorized into the following groups: Group
1 <5 years, Group 2 5-10 years, Group 3 11-15 years, and Group 4 >15 years.

Smoking
The WHO guidelines were used as follows:
i. Current smoker: a person who smokes cigarettes daily or occasionally;
ii. Past-smoker: a person who smoked in the past daily or at occasionally but quit
completely;
iii. Non Smoker: a person who had never smoked or who had smoked very
little in the past. (12)

HbA1c
Levels of HbA1C were assayed using high performance liquid chromatography
(HPLC) method (Bio-Rad). Glycemic control as measured by HbA1c was divided
into two groups according to the ADA (2007):
Group 1: controlled if HbA1c < 7% and
Group 2: uncontrolled if HbA1c 7%.(13)

Hypertension
Blood pressure was measured using standardized sphygmomanometer EN 1060
(RIESTER) with a cuff circumference of 24-32cm to cover 80 percent of the upper
arm. For obese patients, a larger cuff circumference was used (42-50cm). A
trained nurse measured the blood pressure while the subject was in a sitting
position with the arm at the level of the heart and after 5 minutes rest.

Subjects were categorized into two groups:


Group 1: hypertensive, if systolic blood pressure 130 mm Hg or diastolic blood
pressure 80 mm Hg or if the patient is currently using prescribed
antihypertensive drugs;(13)
Group 2: normotensive, if systolic blood pressure <130 mm Hg or diastolic blood
pressure <85 mm Hg.

Age/years
The participants' age was categorized into groups for reasons of comparison. The
categorization was as follows: Group 1 <45 years, Group 2 45-55 years, Group 3
56-65 years, and Group 4 >65 years.

Body mass index (BMI)


Subjects were categorized as normal if BMI was less than 25 kg/m2, overweight
if BMI was between 25-29.9 kg/m2, and obese if BMI was greater than or equal
to 30 kg/m2 (14)

Data management and statistical analysis


Statistical analysis was carried out using Statistical Package for Social Sciences
(SPSS, version 11.5). Frequencies were utilized for categorical variables; means
( standard deviations) were obtained for continuous variables. Chi-square
statistics were used to assess associations. Logistic regression analyses were
performed to estimate the odds ratio (OR) and 95 percent confidence interval
(CI) of selected variables on diabetic retinopathy and its related subdivisions.
Separate regression models were used for non-proliferative DR, proliferative DR,
and maculopathy. A p-value of less than 0.005 was considered statistically
significant.

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Results

Demographic and clinical characteristics of the study population


This study included 1000 patients (510 males, 490 females) with type 2 DM. The
mean age was 57.8 years (SD 9.9), ranging from 27 to 97. Over 40 percent of
patients were within the age group of 56 to 65 years of age. The mean duration
of DM was 9.6 years (SD7.6). Only 22.5 percent had HbA1C <7.0 percent.
About 23 percent were current smokers and 70.6 percent were hypertensive.
More than half of the subjects (56.8 percent) had DM for duration of less than 10
years. Fifty-four and eight tenths percent were obese, and 35.9 percent were
overweight.

Demographic and clinical characteristics of all participants are depicted in Table 1.


In this study, 1.1 percent of patients were treated with diet alone, 34.5 percent
used insulin, 93.1 percent were on oral hypoglycemic drugs, and 28.6 percent
were on a combination therapy of oral hypoglycemic drugs and insulin.

Prevalence of retinopathy
As shown in Table 2a and 2b, 34.1 percent (341) had some form of DR. Of the
total number of patients, 24.5 percent (245) had NPDR, and the type of NPDR
was distributed as follows: mild occurred in 12.1 percent (121), moderate in 7.1
percent (71), and severe in 5.3 percent (53). Seven and eight-tenths percent
(78) had maculopathy. There were no significant differences by gender in
prevalence of any diabetic retinopathy and maculopathy.

As shown in Figure 1, the prevalence of DR increased with age. Almost half of


patients with DM who were >65 years of age had diabetic retinopathy. Figure 2
shows the prevalence of all forms of NPDR according to age and gender. Patients
younger than 45 years old did not have the severe category of non-proliferative
diabetic retinopathy. Figure 3 shows the prevalence of proliferative diabetic
retinopathy according to age and gender. Proliferative diabetic retinopathy was
not noticed before the age of 45 years. For both men and women, PDR increased
with age. The prevalence of maculopathy was higher in men than women for all
age groups as shown in Figure 4.

Factors associated with diabetic retinopathy


Logistic regression analysis of factors associated with DR, NPDR, PDR and
maculopathy after adjustment for other confounders are shown in Table 3.
Diabetic retinopathy was significantly associated with duration of DM (OR=1.21
(95% CI: 1.16, 1.26)) and HbA1C (OR=1.40 (95% CI: 1.17, 1.68)). The odds of
having DR increased by 21% for an increase of one year in the duration of DM
and by 40 percent for each 1 percent increase in HbA1C. Nonproliferative
diabetic retinopathy was significantly associated with duration of DM (OR=1.11
(95% CI:1.07, 1.15)), age (OR=1.03 (95% CI:1.0, 1.6)) and HbA1C (OR=1.40
(95% CI:1.09, 1.6)). The odds of having NPDR increased by 11 percent for an
increase of one year in the duration of DM, 3 percent for each one year increase
in age and 30 percent for each one unit increase in HbA1C. Proliferative diabetic
retinopathy was significantly associated with duration of DM (OR=1.18 (95% CI:
1.12, 1.24)). The odds of having PDR increased by 18 percent for an increase of
one year in the duration of DM. Maculopathy was significantly associated with the
duration of diabetes mellitus (OR=1.08 (95% CI: 1.03, 1.13)). The odds of
having maculopathy increased by 8 percent for every increase of one year in the
duration of DM.

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Table 1
Demographic and important characteristics of 1000
patients with Diabetes Mellitus attending the National
Center for Diabetes Endocrinology and Genetics (NCDEG).

Table 2a
Prevalence of diabetic retinopathy among Jordanian
diabetics by demographic, clinical, other important
characteristics.
Table 2b
Prevalence of diabetic retinopathy among Jordanian
diabetics by demographic, clinical, other important
characteristics.

Figure 1
The prevalence of diabetic retinopathy according to age
and gender. (yrs - years)

Figure 2
The prevalence of all kinds of non-proliferative diabetic
retinopathy according to age and gender.

Figure 3
The prevalence of proliferative diabetic retinopathy
according to age and gender.

Figure 4
The prevalence of maculopathy according to age and
gender.
Table 3
Logistic regression analysis of factors associated with
diabetic retinopathy, non proliferative diabetic
retinopathy, proliferative retinopathy and maculopathy
after adjusting for other factors.

Discussion

The prevalence of DR in patients from the NCDEG using (AAO) (10) and (ICO)
(11) definitions was 34.1 percent. NPDR, PDR, and maculopathy had a prevalence
of 24.5 percent, 9.6 percent, and 7.8 percent, respectively, of the total number of
patients studied. Comparison among studies is difficult because the prevalence of
retinopathy has varied widely depending on the methodology and populations.
The prevalence of DR in this study is comparable to the WESDR.(15) In contrast,
Sparrow et al. (1993) (16) found a higher overall rate of retinopathy (52 percent
versus 34 percent in our study) but a similar prevalence of maculopathy (10
percent versus 7.8 percent in our study). Other studies also have shown similar
prevalence of DR.(17, 18, 19, 20) On the other hand, several studies show a
lower prevalence of DR (21, 22) including two earlier studies from Jordan (8, 9).
In 1999, Salem et al. found that the prevalence of diabetic retinopathy, non-
proliferative diabetic retinopathy, proliferative diabetic retinopathy, and
maculopathy among type 2 diabetics was 50, 38.8, 11.2 and 17 percent,
respectively.(8) The second study by Al Till et al. in 2005 reported the following
numbers: 64.1, 54.8, 9.3 and 30.8 percent, respectively.(9) Our study shows
lower prevalence of DR, NPDR, PDR and maculopathy of 34.1, 24.5, 9.6 and 7.8
percent, respectively. After comparison with the 2005 study, the differences can
be explained by the following possiblities:
i. A difference in the mean duration of DM (12 years in the 2005 study versus 9.5
years in our study);
ii. The exclusion of patients with DM diagnosed less than three years prior in the
2005 study;
iii. The inclusion of type 1 diabetics who are known to have a high incidence of
DR in the 2005 study.
The quality of referral may also impact the above numbers as more patients from
lower socioeconomic areas were included in the 2005 study.
The duration of the disease in the present study was strongly associated with the
frequency of retinopathy, as well as the occurrence of mild, moderate, and severe
non-proliferative diabetic retinopathy and of proliferative diabetic retinopathy.
The prevalence is related primarily to the duration of the disease. Aiello et al. (5)
reported that after 20 year of diabetes, more than 60 percent of type 2 DM will
have retinopathy regardless of diabetic control. This has been confirmed by
numerous other studies.(8, 9, 15, 16, 18-24)

Hyperglycemia (as measured by HbA1C) is considered an important risk factor


associated with DR, and it was significantly associated with retinopathy in our
study. This is consistent with other studies.(7, 9, 15-25) Many studies have
clearly demonstrated the benefits of improving glycemic control by reducing
HbA1C concentration, in decreasing the complication rate. The UKPDS reported
that patients with intensive glucose control had a reduction in retinopathy, a 25
percent drop in the overall microvascular complications, and for every 1 percent
decrease in HbA1C, a 35 percent reduction in risk for microvascular complications
was observed. The authors concluded that slowing the progression of retinopathy
with intensive control resulted in preservation of sight, decreased morbidity and
fewer interventions.(25)

Previous studies differ in relation to the importance of smoking as risk factors.


Multivariate analysis of smoking has not identified it as a risk factor in our
sample. This is similar to WESRD results.(26) On the other hand, some studies
indicated that smoking has been causally related to DR.(27, 28)

Most studies concerning diabetic changes within the eye show that high blood
pressure is significantly associated with diabetic retinopathy and consider
hypertension as an established risk factor for macular edema.(17, 18, 20, 34, 35)
Similarly, major epidemiological studies like WESDR II (15) and UKPDS (25)
report that high systolic blood pressure is significantly associated with
retinopathy. In this study, hypertension showed a significant association with DR
(Chi-square test, p-value < 0.005, see Table 2). However, the regression model
failed to sustain this significant association after multivariate adjustment (see
Table 3) bearing in mind that we depended on the new criteria which considers
systolic blood pressure 130 mm Hg or diastolic blood pressure 80 mmHg
(13). Thus, our results are more in line with the HDS study, which reported that
the frequency of retinopathy was not significant between hypertensive and
normotensive.(36)

The age of the patient was also related to the occurrence of non-proliferative
diabetic retinopathy. Concerning proliferative diabetic retinopathy and
maculopathy, the significance was not maintained after adjusting for the duration
of DM. However, some studies reported a significant association between DR and
age (8, 15). Other studies reported the opposite (20, 28).

Gender was not identified as a risk factor in our study, which agrees with a study
conducted by Janghorbani et al.(30) On the other hand, WESDR concluded that
the severity of DR was related to male sex.(15)

In the present study, BMI showed no significant association with DR and macular
edema. On the other hand, in a population-based cross sectional study by Van
Leiden et al. (2005) (31), the prevalence of DR was positively associated with
BMI. However, other studies reported that the severity of DR was inversely
correlated with BMI, with patients with DR having lower BMIs (32-35 kg/m2).

Limitations
A cross sectional design precludes definitive causal associations; thus, diabetic
retinopathy must be interpreted with caution. Mortality and survival bias is likely,
and a specialized center such as the NCDEG may over estimate the true
population prevalence.

Strengths
Nevertheless, the large database available at NCDEG provides complete data to
study this important problem at minimum time and cost. Using these data, we
answered all questions posed in the objectives.

Conclusion
This is a center-based study exploring the prevalence and risk factors of diabetic
retinopathy among patients attending the NCDEG, a tertiary diabetic center with
referrals from all over Jordan. Though this is not a national-based study, it
highlights the size of the problem. In light of high prevalence of DR, serious
national efforts to reduce DR and its associated vision threatening complications
are needed. These efforts are best directed toward increasing the awareness of
the necessity for regular eye examinations in patients with DM, early detection of
DR and strict glycemic control.

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Acknowledgements

I would like to express my thanks to Professor Kamel Al-Ajlouni for his guidance,
support and above all him being a guardian to this study. He was a mentor
indeed. Special thanks go to Dr. Al-Bdour and Dr.Yousef Al-Kaood for supervising
this study; it would not have been the same without their patience and their
great belief in me. And I owe the team of Dr. Moawea Al-Bdour, especially Dr.
Nakhleh Elias and Dr. Samer Malas, for their cooperation in the ocular
examinations for the patients and the great work they have done which was one
of the main reasons I performed this study.

Sincere thanks go to all staff in the National Center of Diabetes, Endocrinology


and Genetics.
I am grateful to all individuals who participated in this study. I truly wish that the
priceless gift of sight they have wont be affected by diabetes. Thank you, indeed
because you have been the basis for this study.

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References

1. Shaw JE, Zimmet PZ, McCarty D, de Courten M. Type 2 diabetes world wide
according to the new classification and criteria. Diabetes care. 2000; 23 Suppl
2:B5-10.
2. Taylor HR, Keeffe JE. World blindness: a 21st century perspective. Br J
Ophthalmol. 2001; 85: 261-6
3. Linda A, Morton B, Adnan H, Sandra N, Nowak P, Qian Z, Anisa G.
Epidemiology of Diabetes among Arab Americans. Diabetes Care. 2003; 26:308-
13.
4. K. Ajlouni, Y.Khader, A. Batieha, H. Ajluni, M. EL-Khateeb: An increase
prevalence of diabetes mellitus in Jordan during ten years. Accepted for
publication at the Journal of diabetes and its complications.
5. Aiello LP. Gardiner TW, king GL, et al. Diabetic Retinopathy (technicale
review). Diabetes care.1998;21:143-156.
6. Tabbara K, Ross-Dogan D. blindness in Saudi Arabia. JAMA. 1986; 255:3378-
3384.
7. Al Bdour M, Al Till M, Abu Khader I. Causes of blindness among adult
Jordanian, A hospital-based study. Euro J Ophthalmol. 2002; 12(1): 5-10.
8. Salem M, Ajlouni K. Diabtic Retinopathy among Jordanians: It's Patterns,
Severity, and Some Associated Risk Factors. Diabbetologia Croatica. 1999;
28(1):17-23.
9. Al-Till MI, Al-Bdour MD, Ajlouni KM. Prevalence of blindness and visual
impairment among Jordanian diabetics. Eur J Ophthalmol. 2005; 15(1): 62-8.
10. American Academy of Ophthalmology: International Clinical Classification of
Diabetic Retinopathy Severity of Diabetic Macular Edema. Available at:
http://www.icoph.org/pdf/Macular-Edema-Detail.pdf. Accessed January 11, 2006.
11. International Councile of Ophthalmology. ICO international clinical
guideline:diabetic retinopathy (initial and follow up evaluation). Available as at:
http//www.icoph.org/:/guide/guidedi.htmlat. Accessed March 15, 2006.
12. Guideline for controlling and monitoring: the tobacco epidemic. Geneva:
World Health Organization 1998.
13. American Diabetes Association. Standards of Medical care in Diabetes
2007. Diabetes care.2007; 30(suppl 1): S4-S40.
14. World health organization. Physical status: The use and interpretation of
anthropometry: report of WHO expert committee. Technical report series 854.
Geneva: WHO, 1995.
15. Klein R, Klein BEK, Moss SE, et al. The Wisconsin epidemiolgic study of
diabetic retinopathy prevalence and risk of diabetic retinopathy when age at
diagnosis less than 30 years. Arch Ophthalmol. 1984;102:520.
16. Sparrow JM, McCleod BK, Smith TDW, Birch M, Rosenthal R. The prevalence
of diabetic retinopathy and maculopathy and their risk factors in the non insulin
treated diabetic patients of an English town. Eye. 1993; 7:158-63.
17. Kayani H, Rehan N, Ullah N. Frequency of retinopathy among diabetics
admitted in teaching hospital of Lahore. Ayub Med Coll
Abbottabad. 2003;15(4):53-6.
18. Aghadoost D, Sadr F. Prevalence and risk factor for diabetic retinopathy in
diabetic patients of Kashan Diabetic Center in 2002-2003. Feyz. Spring 2005;
33(13):115-20.
19. Abu El Asrar AM, Al-Rubeaan KA, Al-Amro SA, Kangave D, Moharram OA. Risk
factors for diabetic retinopathy among Saudi diabetics. Int Ophthalmol. 1999;
22:155-61.
20. El Haddad OA, Saad MK. Prevelance and risk factors for Diabetic Retinopathy
among Omani Diabetics. Br J Ophthalmol. 1998; 82:901-6.
21. Robyn J. Jonathan E. Alex H, et al. The prevalence of and factors associated
with diabetic retinopathy in the Australian Population. Diabetes care. 2003;
26(6):1731-37.
22. Al-Shammari F, Al-Meraghi O, Alfred N, Al-Otaibi S. The prevalence of
retinopathy and associated risk factors in type 2 diabetes Mellitus in Al-Naeem
area: Kuwait. Middle East journal of family medicine. 2005; 3(2):42-48.
23. Diabetes Control and Complications Trial Research Group. The effect of
intensive treatment of Diabetes on the development and progression of long-term
complications in Insulin-dependent DM.N Engl J Med. 1993; 329:977-86.
24. Segato T, Midena E, Grigoletto F et al. the epedimiology and prevalence of
diabetic retinopathy in the Veneto region of North East Italy. Veneto group for
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25. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of
macrovascular and microvascular complications in type 2 diabetes: UKPDS
38. BMJ. 1998;317:703-713; erratum 1999;38:29.
26. Moss SE ,KleinR,Klein BEK:Aassociation of cigarette smoking with diabetic
retinopathy. Diabetes Care. 1991:14:119.
27. Ballard DJ, Melton LJ, Dwyer MS, et al. Risk factor for diabetic retinopathy: A
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28. Paetkau ME, Boyd TAS, Winship B, Grace M. Cigarette smoking and diabetic
retinopathy.Diabetes. 1977;26:46-49.
29. Agarwal S, Raman R, Kumari R, et al. Diabetic retinopathy in type II diabetics
detected by targeted screening versus newly diagnosed in general practice: Ann
Acad Med Singapore. 2006; 35(8):531-5.
30. Janghorbani M, Amini M, Ghanbari H, Safaice H. Incidence of and risk factors
for diabetic retinopathy in Isfahan, Iran. Ophthalmic Epidemiol. 2003; 10:81-95.
31. Van leiden HA, Dekker JM, Moll AC, Nijpels G, Heine R, Bouter L, et al. Blood
pressure, lipid and obesity are associated with retinopathy: the hoom
study. Diabetes care. 2002;25(8):1320-5.
32. Klein R, Klein BEK, Moss SE, Davis M, Demetes D. The Wisconsin
epidemiologic study of diabetic retinopathy II. Prevalence and risk of diabetic
retinopathy when age at diagnosis 30 or more years. Arch
Ophthalmol. 1984;102:527-32.
33. Teruel M.C, Frenandez-Real JM, Ricart W, Valent Ferrer R, Valles Prats M.
Prevalence of diabetic retinopathy in the region of Girona study of related
factors. Arch Soc ESP Oftalmol. 2005; 80(2):85-91.
34. Metrreveli DS, Sudkhanishvili MZ, Margvelashvili MZ. The prevalence of
diabetic retinopathy in subjects with type 2 diabetes of one year and less
duration. Georgian Med News. 2006; 132: 64-8.
35. Leske MC, Wu SY, Hennis A, Hyman L, N emesure B, Yang L, et al.
Hyperglycemia, blood Pressure, and the nine year incidence of diabetic
retinopathy: the Barbados eye studies.Ophthalmology. 2005; 112 (5):799-805.
36. Hypertension in Diabetes Study (HDS): I. Prevalence of hypertension in newly
presenting type 2 diabetic patients and the association with risk factors for
cardiovascular and diabetic complications: The Hypertension in Diabetes Study
Group. J Hypertension;1993,11:309-317.

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Copyright 2015. All rights reserved. Reproduction in whole or in part in any form or
medium without expressed written permission of the Digital Journal of Ophthalmology is
prohibited.
Keratouveitis Following A Contralateral
Herpes Zoster Ophthalmicus
Printer Friendly
Digital Journal of Ophthalmology 2007
Volume 13, Number 1
July 9, 2007

Mohamad Aziz Salowi | Selayang Hospital


Wan Zalina Zain | Selayang Hospital

ABSTRACT INTRODUCTION MATERIALS AND


METHODS RESULTS DISCUSSION REFERENCES

Abstract

Objective
To report a patient who had previous unilateral herpes zoster ophthalmicus
presenting with contralateral ocular involvement.

Methods
Case report

Results
A 47 year-old woman presented with a unilateral, painful, red eye preceded by a
painful rash over her contralateral forehead and nose. Examination revealed a
healed herpes zoster rash on the right forehead and tip of the nose associated
with left eye keratouveitis. Examination of the right eye did not reveal any
abnormality despite being on the same side with the facial scar. She was treated
with topical antiviral drops with subsequent topical steroid. After one week of
treatment, vision improved to 6/12. She had completely recovered one month
later. A faint corneal scar was present inferonasally that did not involve visual
axis. The final visual acuity in the left eye was 6/9.

Conclusion
We propose a careful ophthalmic examination in both eyes in patients with herpes
zoster ophthalmicus in view of the possibility of contralateral eye involvement.
Keywords
Contralateral, Herpes Zoster Ophthalmicus, Keratouveitis

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Introduction

Involvement of the ophthalmic branch of trigeminal nerve by herpes zoster can


cause various ocular complications. We report a patient who had unilateral herpes
zoster ophthalmicus presenting to us with contralateral ocular involvement.

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Materials and Methods

Case report

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Results

A 47 year-old woman was referred for unilateral painful red eye associated with a
decrease in vision. The symptoms were preceded by a painful rash over her
contralateral forehead and nose one week earlier. She was an otherwise healthy
lady with no known medical problems.

At presentation, there was a facial scar on the right forehead and the tip of nose
corresponding to the dermatomal distribution of the ophthalmic division of the
trigeminal nerve. The lids were spared. (Figure 1) Examination of the left eye
revealed vision of 6/60, with pinhole improvement to 6/36. The corneal sensation
was decreased. There were paracentral Descemets folds at the 5 oclock position,
measuring 3mm by 3mm with very mild stromal edema, endothelial bullae and
localized keratic precipitates. The anterior chamber showed mild inflammation.
The pupil was otherwise reactive and round. (Figure 2) The intraocular pressures
and ocular movement in both eyes were normal. Visual acuity in the right eye
was 6/9. The examination of the right eye did not reveal any abnormality despite
being on the same side with the facial scar.
The distribution of the facial scar was characteristic of herpes zoster ophthalmicus
(HZO) with a possible relation to the left eye keratouveitis. Topical antiviral
(Acyclovir) with subsequent topical steroid were prescribed. She was also given
analgesia for residual right sided facial pain. After one week of treatment, the
vision improved to 6/12 in the left eye. The corneal edema and striae were
markedly reduced and the bullae the on endothelium had completely resolved.

She completely recovered one month later. There was no more facial pain. A faint
corneal scar was present inferonasally that did not involve the visual axis. The
final vision in the eye left was 6/9.

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Discussion

Herpes zoster, commonly known as shingles, is caused by reactivation of latent


varicella-zoster virus (VZV) present in sensory ganglia after chicken pox
infection.(1) Any sensory ganglion may be involved but the dermatomes most
commonly affected, in order of frequency, are thoracic, cranial, cervical, lumbar
and sacral.(1, 2) Herpes Zoster Ophthalmicus (HZO) involves the dermatome
innervated by the ophthalmic division of the trigeminal nerve and accounts for
20% of all cases of Herpes Zoster.(3)

HZO differs from other types of herpes zoster because of the likely involvement
of the globe itself as opposed to herpes zoster in other dermatomes which is
typically limited to localized cutaneous disease. Corneal involvement may
complicate HZO in 34% of cases. It can manifest concurrently with the disease or
present later. One such example is keratouveitis which has a typical onset of
seven days after HZO.(1, 2, 4)

Nakanishi et al. reported a patient who developed acute retinal necrosis (ARN) in
the contralateral eye following HZO.(5) There was also a reported case of an
immunocompromised patient who had a unilateral HZO with ipsilateral ocular
blindness and subsequently developed encephalitis and antegrade spread of VZV
through the visual system resulting in bilateral blindness.(6) However, to the best
of our knowledge, keratouveitis in contralateral eye following HZO has not been
previously reported.

The possible explanation for corneal involvement in our patient is direct


cytopathic effect of the virus and corneal immune response to replicating viral
particles.(1, 2) The pathogenesis, however, for contralateral ocular involvement
is obscured. Our patient might have had a bilateral HZO with insufficient dermal
findings on the left side.

In most situations, diagnosis of HZO can be established from the characteristic


rash.(1) Invasive laboratory investigations are reserved only for those atypical
cases of HZO.(1) In our patient, they were obviously contraindicated in view of
the presence of a good visual potential and good response to treatment.
Apart from presenting early during the course of the disease, grave complications
such as ARN, meningitis, encephalitis and cerebral infarct may occur later hence
the need for an appropriate follow up for patients with HZO.(1, 5, 6)

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References

1. Krachmer, Mannis, Holland. Cornea and External Disease: Clinical Diagnosis


and Management. Cornea: Mosby, 1997:1225-1242.
2. Looney BD. Herpes Zoster Ophthalmicus. Clinical Eye and Vision Care
1997;9:203-211.
3. Rogazzino MW, Melton, Kurland LT. Population-based study on herpes zoster
and its sequela. Medicine 1982;61:310.
4. Marsh K, Cooper M. Ophthalmic herpes zoster. Eye 1993;7:350-370.
5. Nakanishi F, Takahash H, Ohara K. Acute Retinal Necrosis Following
Contralateral Herpes Zoster Ophthalmicus. Japanese Journal of Ophthalmology
2000;44(5):561-564.
6. Rostad SW, Olson K, McDougall J, Shaw C-M, Alvord EC. Transsynaptic spread
of varicella zoster virus through the visual system: A mechanism of viral
dissemination in the central nervous system. . Human Pathology
1989;20(2):174-179.

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Figure 1
Facial scar at the dermatomal distribution of ophthalmic
division of right trigeminal nerve

Figure 2
Left eye keratouveitis

Copyright 2015. All rights reserved. Reproduction in whole or in part in any form or
medium without expressed written permission of the Digital Journal of Ophthalmology is
prohibited.
Aqueous shunt to the ocular surface for
severe dry eye
Printer Friendly
Digital Journal of Ophthalmology 2005
Volume 11, Number 2
March 9, 2005

Claes Dohlman, M.D. | Massachusetts Eye and Ear Infirmary, Schepens Eye
Research Institute, Harvard University
Jan Dohlman, M.D. | East Boston Neighborhood Health Center, Boston University

ABSTRACT INTRODUCTION MATERIALS AND


METHODS RESULTS DISCUSSION ACKNOWLEDGEMENTS REFERENCES

Abstract

Objective
In very dry eyes from any etiology, there is a need for near-continuous fluid
supply to the ocular surface. Here is presented a patient with severe dry eyes
who had a double-tubed valve shunt implanted to divert the aqueous humor to
the lower lid fornix, thereby wetting the eye. Such arrangement has previously
been used in eyes with keratoprosthesis and glaucoma.

Methods
A 67 year old woman had been severely incapacitated with pain and photophobia
for many years. Tear menisci were virtually absent, Schirmer values were
repeatedly zero, and vision was reduced in one eye. Etiology seemed to be
scarring of lacrimal gland ductules caused by vernal catarrh.

Results
The shunt was implanted without complications, immediately resulting in wetting.
After 6 months the eye is totally quiet and comfortable, with 20/25 vision and
mild epiphora due to obstructed canaliculi. The tube in the lower fornix is rarely
felt. Antibiotic drops are given twice daily and no infection has occurred.

Conclusion
So far the patient has done well with a totally quiet and wet eye. The only
complication has been epiphora. If the long-term risks are low, this principle may
be of value in end-stage dry eyes such as in autoimmune diseases, chemical
burns, and trachoma.

Keywords
dry eye, aqueous shunt

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Introduction

Very severe dry eyes without any visible tear secretion are common in chronic,
end-stage inflammatory and scarring conditions of the ocular surface.
Autoimmune diseases, such as ocular cicatricial pemphigoid (OCP), Stevens -
Johnson syndrome (SJS), graft-versus-host disease (GVHD), as well as severe
chemical burns, can end up with totally dry keratinized corneas. In addition,
longstanding trachoma, vernal catarrh and other chronic inflammatory ocular
surface conditions common worldwide can likewise lead to severe dryness.
The cause of the surface dryness would be expected to be scar formation around
the lacrimal ductules from the lacrimal gland and accessory glands, obstructing
the flow from otherwise normal lacrimal gland tissue. This is in contrast to the
much more common situation in e.g. Sjgrens syndrome where the gland itself
becomes inflamed and dysfunctional but where the tear secretion rarely ceases
completely.

Therapeutic options to wet the ocular surface in the most severely dry eyes are
few. The canaliculi have usually already scarred close, obstructing outflow.
Tarsorrhaphy has limited value and scleral lenses are difficult to fit, expensive,
and only rarely successful in the long run. This leaves artificial tear solutions as
drops as the only practical alternative but with limited retention time and
effectiveness. Treatment of the inflammatory component of the underlying
disease has usually at this stage failed to prevent the final dryness. Therefore the
possibility of providing a continuous flow of fluid over the ocular surface in dry
eyes has intrigued ophthalmologists for decades. Thus spray pumps, attached to
spectacle frames, have been developed with increasing sophistication(1,2). Also,
pump systems leading fluid to the fornices via subcutaneously placed tubings
have been tested (3-5). Transposition of salivary gland ducts to the lower lid
fornix is surgically possible but the unevenness of the salivary secretion during
the day has been a problem (6). Autotransplantation of submandibular gland is a
more recent and promising approach (7).

Another principle for establishing continuous fluid delivery to the ocular surface
could be the diversion of aqueous humor to the lid formices. Some recent
developments in glaucoma shunt technology might accomplish such arrangement.
Standard glaucoma shunt plates can become enclosed by a dense capsule,
causing the intraocular pressure to rise to unacceptable levels. Diverting the
aqueous humor to nearby epithelialized cavities where a fibrous capsule is less
likely to form, has been shown to bypass the problem. Past research on this
principle has included experiments in monkeys(8) and a patented device (9).
More recently this concept has been tested in humans with severe glaucoma after
keratoprosthesis surgery (10-12). Thus valved tube shunts have been implanted
in patients, diverting the aqueous humor to a nasal sinus or to the lower lid
fornix. Only one very recent infection has occurred in 32 such patients (8 with
tubes to the fornix), with a follow-up time of up to 3 years (cumulatively 54
shunt years). This development opens the possibility of using such valve shunts
to the lid fornix in severe dry eyes as well. Here we describe the initial outcome
of such a procedure in a patient who for many years has suffered from
debilitating keratoconjunctivitis sicca.

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Materials and Methods

The patient is a 67 year old woman with a history of several decades of


increasingly severe irritation in both eyes (Fig. 1). The diagnosis of dry eyes was
made over 20 years ago. All puncta had been closed, the lower cauterized, and
the upper had plugs. The patient was at the time of examination so incapacitated
that she had to wear dark glasses and she used more than one bottle of artificial
tears per day for instillation which still gave her only momentary relief. She was
otherwise healthy and she had no symptoms of dry mouth or rheumatoid
arthritis. On examination visual acuity was found to be 20/70 in the right eye and
20/20 in the left. Intraocular pressures were 8 and 10 mm Hg respectively, by
applanation tonometry. Schirmer tests were repeatedly 0 mm/5 minutes, with
anesthesia, in both eyes. Slit lamp examination revealed virtual absence of tear
menisci (Fig 2). Fluorescein staining showed superficial punctate keratitis in the
right cornea, less in the left.

Examination of the tarsal conjunctivae suggested the etiology of the condition.


There was a whitish subepithelial sheen, indicating diffuse scarring from healed
vernal conjunctivitis (difficult to photograph). On further questioning, the patient
remembered severe eye problems for several years during her childhood.

The patient underwent examination by a rheumatologist (JGD). No history of


systemic connective tissue disease could be elicited and the patient appeared
healthy. Sedimentation rate was 15 mm, ANA screen negative, rheumatoid factor
was normal, SS antigens negative. The hematological profile was normal. There
was no history of dry mouth. On the basis of these findings, Sjgrens syndrome
appeared unlikely.

The possibility of implanting a valve shunt diverting aqueous to the lower lid
fornix, thereby wetting the ocular surface, was discussed in detail with the patient
who desired to have the operation done in her worse, right eye. Extensive
informed consent for the operation was obtained preoperatively and the
Institutional Review Board was consulted. The surgery consisted of implanting a
valve shunt which had been manufactured at our request by New World Medical,
Inc. (Rancho Cucamonga, CA). The shunt, previously described (11,12), consists
of a proximal fine tube of silicone to be inserted to the anterior chamber. It
connects to a valve similar to that of a standard Ahmed S-2 valve shunt, made
for an opening pressure of 10 12 mmHg. Our shunt did not have a plate but
rather the valve was enclosed by a silicone rubber housing. From the side of this
housing a distal tube emerges to be drawn up to the lower lid fornix (Fig. 3).

The proximal tube to the anterior chamber was inserted beneath a half-depth 4
mm scleral flap, entering into the anterior chamber through a 23 g needle track
of the limbus. The tube extended approximately 3 to 4 mm into the anterior
chamber and was positioned anterior to the iris (Fig. 4). The valve housing was
sutured to the sclera in the lower nasal quadrant with two 9-0 nylon sutures, in a
manner similar to the attachment of a standard S-2 shunt plate. The distal tube
was tied to a 4-0 silk suture and the needle was passed temporally under the
conjunctiva to about midpoint of the fornix where it was exited upwards, and the
tube was pulled through. The tube was cut so that it was allowed to lie flat in the
fornix, extending for about one centimeter. Two 10-0 nylon sutures were placed
to temporarily keep the tube flat at the bottom of the fornix. Aqueous could
immediately be seen trickling out of the tube opening. A soft contact lens (Kontur
16.0 mm diameter, 9.8 mm base curve, plano, Kontur Kontact Lens Co, Inc.,
Richmond, CA 94801) was finally placed on the eye. It was kept for 2 weeks in
order to keep the patient more comfortable.

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Figure 1.
67-year old female with many years of marked discomfort
from very dry eyes.

Figure 2.
Virtual absence of tear menisci (fluorescein staining).
Schirmer values repeatedly 0 mm /5 minutes. Superficial
punctate keratitis. Vision 20/70.

Figure 3.
Valved tube shunt. The short tube is inserted into the
anterior chamber. The valve is totally enclosed in silicone
rubber and is attached to the sclera in the lower nasal
quadrant. The long tube is drawn temporally through the
conjunctiva, shortened and left at the bottom of the lower
lid fornix. Aqueous is then delivered continuously to the
fornix and distributed over the surface of the eye by blinking.
Figure 4.
Post-operative appearance. Since puncta and canaliculi
had been obliterated earlier, the lower lid tear meniscus is
voluminous and there is mild epiphora. The corneal
epithelium has healed and the vision is restored. The
intraocular tube is visible in the 5 oclock meridian.

Figure 5.
The distal tube is visible at the bottom of the lower lid
fornix where it is rarely felt. The eye is quiet and there is
no conjunctival reaction.

Results

Postoperatively the patient did well with a minimum discomfort for a few days. In
fact, she felt instantaneous relief when the lower tear meniscus welled up (Fig.
4). She reported occasional epiphora (the puncta had been left closed). Schirmer
tests postoperatively varied from 5 mm to 17 mm in 5 minutes, with anesthesia.
After one month visual acuity had increased to 20/25. The intraocular pressure
has been measured at between 5 mm and 9.5 mm by applanation tonometry.
There has been no shallowing of the anterior chamber, hypotony maculopathy, or
other complications of hypotony.

The patient initially received vancomycin (14 mg/ml), moxifloxacin 0.5 % and
prednisolone acelate 1 %, all topically four times daily. This regimen was over a
month lowered to twice a day. Three weeks postoperatively an attempt was made
to open the right upper punctum to relieve the epiphora. Dissection under local
anesthesia by an ophthalmic plastic surgeon, Dr. Peter Rubin, resulted in removal
of the plug stem but the caniliculus remained scarred and obliterated. A re-
canalization procedure is planned for the future.

Later in the minor operating room under topical anesthesia, the tube was
shortened to about 5 mm exposed length. An additional 10-0 nylon suture was
placed to keep the tube at the bottom of the fornix (Fig. 5). The patient has
during the follow-up period of 6 months felt substantial relief in the operated eye
and she is, so far, satisfied with the outcome.

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Discussion

The encouraging aspect of this patients short-term follow-up is not only that the
aqueous humor wets the external eye surface so well but also that the eye rapidly
became very quiet without irritation. The relief was almost instantaneous after
the operation. Also, the exit tube is very rarely felt at the bottom of the lower lid
fornix, only if the eye is rubbed. This was expected from our experience with fluid
delivery via a subcutaneous tube to the lower lid fornix(3,4).

The only, fortunately minor, side effect has been epiphora, due to the obliterated
canaliculi. In severely dry eyes, such as in end-stage autoimmune diseases, the
puncti and canaliculi are usually completely scarred down. Surgical recanalization
is very difficult in these cases and epiphora may be the price to pay for the
continuous wetting of the eye. On the other hand, if the canaliculi are open, it has
been our experience that glaucoma patients with fornix shunt do not report
epiphora during the day. Occasionally they describe some wetness on the pillow
when they wake up in the morning. This is probably explained by the fact that
aqueous is secreted continuously around the clock (2 uL/min(13)). Tear
production during the day has similar value but the night-time secretion is
markedly reduced (14). Thus the slight epiphora during the night is likely due to
uninterrupted aqueous secretion and absence of blink pump during sleeping
hours.

What are the potential long-term risks in this technique of diverting aqueous to
the lid fornix? First, there must be the usual risks of glaucoma shunts such as
tube or valve erosion and exposure, intraocular tube damage to the corneal
endothelium, intraocular obstruction of the tube, or, rarely, infection. Then the
added risk of infection due to the connection with the conjunctival surface must
be considered. However, based on previous experience with valve shunts ending
in the nasal sinuses or lower lid fornix, the risk of endophthalmitis seems low. In
more than 50 cumulative shunt years only one recent infection has occurred.
These valved tube shunts seem to have unidirectional flow, thus fluid cannot in
vitro be forced from the distal end to exit through the proximal tube opening. It is
unlikely that the low dose prophylactic antibiotics (vancomycin plus a
fluoroquinolone once or twice a day) which are given routinely after
keratoprosthesis (with or without shunt), could prevent infection if a bacterial
bolus managed to reach the inside of the eye. This suggests that it is the
unidirectional flow of the aqueous that reduces the risk of infection.

There could still be the risk of infection around the stoma in the conjunctiva
where the distal tube exits into the fornix. After all, the normal conjunctiva is the
host of a number of bacteria such as Staphylococcus epidermidis and
Corynebacteria species, as well as Haemophilus, Moraxella, Proprionobacterium
acnes, etc (15). Again no infection has occurred in the tissues around the tube
exit in altogether 9 cases of valve shunt to the lower fornix, followed for up to 20
months. Here it is quite possible that the routinely given topical antibiotics do
manage to suppress bacterial colonization and infection. Clearly a future step in
the development of this shunt-to-fornix method will have to be trying to minimize
use of antibiotics.

The described principle of wetting the ocular surface with aqueous is technically
feasible. It may find some application in the end-stage autoimmune diseases
where epithelial inflammation may be the basis for the disease process but where
lack of fluid may also play a large role.

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Acknowledgements

Presented at the International Symposium on Lacrimal Gland, Tear Film, and Dry
Eyes 4, held in Puerto Rico November 2004.

Supported by a grant from Alcon Research Institute.

Corresponding author:
Claes H. Dohlman, M.D., Ph.D
Massachusetts Eye and Ear Infirmary
243 Charles Street
Boston, MA 02114
Tel: (617)573-3240
Fax: (617)573-4369
Email: Claes_Dohlman@meei.harvard.edu

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References

1. Flynn F, Schulmeister A: Keratoconjunctivitis Sicca and new techniques in its


management, Med J Austral 1967; 1:33-41

2. Bertera JH, Dohlman CH, Ma JK Programmable microdroplet dispenser


functions as an artificial lacrimal gland. (ARVO abstract). Invest Ophthalmol Vis
Sci 2003;2451.

3. Dohlman CH, Doane MG, Reshmi CS: Mobile infusion pumps for continuous
delivery of fluid and therapeutic agents to the eye. Ann Ophthalmol 1971;3:126-
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