Original Article

Dermatological Findings in Glaucoma Patients:
Comparison Between Pseudoexfoliative and Primary

Open-angle Glaucoma

Farnaz Ahmadpour1, MD; Yalda Nahidi1, MD; Ramin Daneshvar2,3, MD, MS

1Department of Dermatology, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
2Eye Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, FL, USA

ORCID:
Farnaz Ahmadpour: https://orcid.org/0000-0001-8853-1348
Ramin Daneshvar: https://orcid.org/0000-0002-0884-0907

Abstract

Purpose: To compare the frequency of dermatological manifestations between
patients with pseudoexfoliative glaucoma and those with primary open-angle
glaucoma.
Methods: A cross-sectional study was done on all consecutive pseudoexfoliative
glaucoma (PEXG) and primary open-angle glaucoma (POAG) patients evaluated
in a tertiary eye hospital during the study period. Eligible patients were referred
to the dermatology department for complete skin, hair, nail, and mucosal
examinations.
Results: Twenty-one patients in the PEXG group and 26 patients in the POAG
group were included in this study. The most common skin manifestations in the
study were seborrheic dermatitis, dry skin, and cherry angioma. The frequency of
lentigines was significantly higher in the PEXG patients than in the POAG group (P
= 0.013). More than half of the study population had seborrheic dermatitis (57.1%
and 61.5% in the PEXG and POAG groups, respectively); however, the difference
between the groups was not statistically significant (P = 0.775). Similarly, the
frequencies of skin dryness, cherry angioma, nevus, psoriasis, contact dermatitis,
itching, seborrheic keratoses, notalgia paresthetica, and vitiligo in the two groups
were not statistically significantly different (P > 0.1 for all comparisons). There
was no significant association between the frequency of the investigated skin
manifestations and patients’ age, visual acuity, intraocular pressure, and cup-to-
disc ratio.
Conclusion: Integumentary system disorders are pervasive in glaucoma patients,
and dermatologic evaluation in glaucoma patients should be considered for
diagnostic and therapeutic purposes.

Keywords: Dermatitis; Dermatologic Finding; Glaucoma; Open-angle Glaucoma;
Pseudoexfoliation

J Ophthalmic Vis Res 2022; 17 (4): 479–485

© 2022 Ahmadpour et al. THIS IS AN OPEN ACCESS ARTICLE DISTRIBUTED UNDER THE CREATIVE COMMONS ATTRIBUTION LICENSE | PUBLISHED BY KNOWLEDGE E 479

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Dermatological Manifestations in Glaucoma Patients; Ahmadpour et al

INTRODUCTION

Pseudoexfoliation syndrome (PEXS) is a systemic
condition. Many organ involvements, including
lungs, heart, liver, gallbladder, kidneys, blood
vessels, meninges, ear, optic nerves, eye,
and eyelid skin have been reported in this
syndrome.[1–5] Histologic studies confirmed the
presence of pseudoexfoliative materials in various
tissues; nevertheless, the exact composition of
these materials and their pathogenesis are still
unknown. In ocular structures, these materials
manifest as a group of proteins in the form
of granular shells that resemble dandruff.[6, 7]
Build-up of these materials within the eye can
result in pseudoexfoliative glaucoma (PEXG),
the most common secondary type of open-
angle glaucoma.[8] Similar to the situation in the
eye, there is evidence that pseudoexfoliative
substances are also present in large areas of the
skin and viscera.[3, 9, 10] However, there is still a lack
of sufficient data about the characteristics of the
manifestations of PEXS in the skin.

On the other hand, primary open-angle
glaucoma (POAG) is the most common type of
glaucoma in general worldwide.[11] Treatment
with topical eye drops, which is usually the
first line of management for glaucoma patients,
can cause a wide range of systemic adverse
effects, including disseminated skin eruptions.[12]
Interestingly, skin involvement is among the most
common comorbidities in all forms of glaucoma.[13]
However, dermatologic disease and adverse
skin reactions caused by eye drops used in
treating glaucoma have not been described
sufficiently.[14] Medical management of POAG
and PEXG is usually the same, and one should
expect similar drug-related skin manifestations
in these two groups. As the pseudoexfoliative
substance in ocular structures has also been found

Correspondence to:

Ramin Daneshvar, MD, MS. Eye Research Center,
Khatam Anbia Eye Hospital, Ghareni Blvd., Mashhad
91959, Iran.
Email: radaneshvar@gmail.com
Received: 06-01-2022 Accepted: 28-04-2022

Access this article online

Website: https://knepublishing.com/index.php/JOVR

DOI: 10.18502/jovr.v17i4.12298

in skin, it seems reasonable to expect
some additional clinical manifestations on
dermatological evaluation of PEXG patients.
To the best of our knowledge, no study has
been published specifically on the clinical
dermatological manifestations of patients with
PEXS.

The primary purpose of this cross-sectional
study was to describe clinical findings in the
dermatologic evaluation of patients with PEXG and
to compare them with those patients with POAG.
Our working hypothesis was that the prevalence
of specific dermatological manifestations that
occur in the PEXG group might differ from
those that occur in the POAG group. As the
medical management is the same between
PEXG and POAG, any variations discovered
in dermatologic findings may highlight some
probable associations with underlying pathology.
Furthermore, as PEXG is highly prevalent in
the elderly population in Iran,[15] research on its
multiple clinical manifestations seems relevant.
We can better understand this syndrome and
its various clinical presentations by identifying
skin manifestations of PEXS patients. This
discovered correlation can also help with timely
diagnosis and management of the associated
glaucoma.

METHODS

This was a cross-sectional study in the
Ophthalmology and Dermatology Departments of
Mashhad University of Medical Sciences (MUMS),
Mashhad, Iran, between April and September 2019.
Consecutive patients with a clinical diagnosis of
PEXG or POAG were referred from the Glaucoma
Clinic of Khatam Anbia Eye Hospital to the
Dermatology Clinic of Emam Reza General Hospital
for a thorough dermatologic evaluation. The study
adhered to the tenets of the Declaration of Helsinki,

This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.

How to cite this article: Ahmadpour F, Nahidi Y, Daneshvar
R. Dermatological Findings in Glaucoma Patients: Comparison
Between Pseudoexfoliative and Primary Open-angle Glaucoma. J
Ophthalmic Vis Res 2022;17:479–485.

480 JOURNAL OF OPHTHALMIC AND VISION RESEARCH Volume 17, Issue 4, October-December 2022

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Dermatological Manifestations in Glaucoma Patients; Ahmadpour et al

and all included subjects provided written informed
consent before participation. The Medical Ethics
Committee at MUMS approved the study protocol
(IR.MUMS.fm.REC.1394.646).

All glaucoma diagnoses were made by a single
glaucoma-fellowship-trained ophthalmologist
(RD). The diagnosis of glaucoma was based on
characteristic optic nerve damage and/or visual
field defect in the presence of high intraocular
pressure (IOP) or a normal IOP with a history of
either IOP-lowering medications, laser procedures,
or surgeries. The PEXG was diagnosed based
on the presence of glaucoma with any of the
following findings: pseudoexfoliative material at
the edge of the pupil and/or anterior capsule
of the lens after complete mydriasis, atrophy
of the pupillary sphincter, Zentmeyer line on
the anterior lens capsule, or Sampaolesi line
in gonioscopy. In contrast, those with POAG
had a wide-open angle with normal angle
pigmentation on non-indentation gonioscopy
and without any finding of or underlying cause for
secondary glaucoma. Exclusion criteria comprised
any possible secondary causes of glaucoma,
including pseudoexfoliation, history of using
steroid medications or Cushing’s syndrome at any
time, history of trauma to the eye, history of retinal
vascular disease, history of radiotherapy, history
of uveitis, and history of intraocular surgery. Also,
we excluded patients with skin conditions known
as direct therapeutic side effects, such as allergic
contact dermatitis, due to glaucoma drops.

Patients were referred to Imam Reza General
Hospital for a complete skin examination. At
the Dermatology Clinic, all subjects underwent
a thorough dermatologic evaluation, including a
complete examination of the skin, hair, nails,
and mucosa by one expert dermatologist (YN).
If needed, a skin smear or biopsy was used
to confirm the diagnosis of cutaneous disease.
All findings were recorded with a particular
focus on the frequency and types of exfoliative
manifestations (such as psoriasis and seborrheic
dermatitis) in skin, hair, nails, and mucosa.

Central tendency measures were used to
summarize the quantitative variables. Normal
distribution of data was examined using the
Shapiro–Wilk test and normality plots, and based
on that, either the student t-test or Mann–
Whitney U test was used to compare the two
groups. Qualitative data was presented by their
frequencies and percentages and compared

between the groups using the chi-square test.
All statistical analyses were performed with
SPSS software (Version 18, IBM SPSS Statistics,
IBM Corporation, Chicago, IL, USA). Statistical
significance was set at a P < 0.05 level, and the
significance level was adjusted for multiple
comparisons with Bonferroni correction as
appropriate.

RESULTS

In this study, a total of 47 subjects were enrolled,
including 21 PEXG and 26 POAG cases. Seven
patients in the PEXG group and 12 in the POAG
group were females (P = 0.551). Patients with POAG
were younger than those with PEXG (58.4 ± 15.2 vs
66.7 ± 8.3 years, P = 0.023). More POAG patients
were in the range of 30–50 years (8 vs 2 in PEXG);
however, the age distribution was almost similar
for the 51–70 years and 71–90 years age groups.
There was no significant difference in visual acuity
(VA), IOP, and cup:disc ratio (CDR) between the two
groups [Table 1].

All PEXG patients and 24 (92.3%) POAG patients
had at least one abnormal dermatological finding
(P = 0.495). The most common dermatological
manifestations in patients with PEXG were
seborrheic dermatitis, dry skin, and cherry
angioma. Other dermatologic manifestations
of these patients included idiopathic guttate,
hypomelanosis on the trunk and limbs, xeroderma
pigmentosome and severe aging, lentigo maligna,
and cafe au lait macules. In those with POAG,
the most common dermatological findings
were seborrheic dermatitis, cherry angioma,
and dry skin. Other specific manifestations
seen in these patients included androgenic
alopecia, telogen effluvium due to acetazolamide,
nail-biting, pityrosporum folliculitis, sebaceous
hyperplasia, nail fungal infection, alopecia areata,
photosensitivity, macular amyloidosis, lipoma, and
venous lake. Table 2 represents the frequency of
different dermatologic manifestations in the study
participants.

Moreover, 12 patients with PEXG and 16 with
POAG had seborrheic dermatitis (P = 0.775). One
patient in the PEXG group and two in the POAG
group had seborrheic findings on both head and
face.

Eleven patients in the PEXG group and seven
in the POAG group had dry skin manifestations,

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Dermatological Manifestations in Glaucoma Patients; Ahmadpour et al

Table 1. Baseline clinical characteristics of patients included in the study.

PEXG POAG P-value*

Number of subjects 21 26

Male: Female 14:7 14:12 0.551

Age, yr (Mean ± SD) 66.7 ± 8.3 58.4 ± 15.2 0.023
Age groups (yr) 30–50 2 8 0.150

51–70 9 11 0.970

71–90 10 7 0.146

VA, logMAR (Mean ± SD) OD 0.28 ± 0.29 0.21 ± 0.22 0.466
OS 0.18 ± 0.23 0.22 ± 0.23 0.452

IOP, mmHg (Mean ± SD) OD 15.7 ± 6.0 15.2 ± 4.1 0.838
OS 16.0 ± 6.1 14.2 ± 2.3 0.488

CDR (Mean ± SD) OD 0.72 ± 0.19 0.66 ± 0.22 0.330
OS 0.74 ± 0.22 0.67 ± 0.23 0.240

LP or NLP eyes 5 2 0.217

OD, oculus dexter (right eye); OS, oculus sinister (left eye); CDR, cup: disc ratio; IOP, intraocular pressure; PEXG,
pseudoexfoliative glaucoma; POAG, primary open-angle glaucoma; LP, light perception; NLP, no light perception; logMAR,
logarithm of minimum angle of resolution; SD, standard deviation
∗Significant P-value with Bonferroni adjustment is <0.004

Table 2. Frequency of dermatologic manifestations in the study groups.

PEXG (n = 21) POAG (n = 26) P-value*

Seborrheic dermatitis 12 (57.1%) 16 (61.5%) 0.775

Dry skin 11 (52.4%) 7 (26.9%) 0.130

Cherry angioma 8 (38.1%) 9 (34.6%) 0.990

Nevus 1 (4.8%) 3 (11.5%) 0.617

Psoriasis 1 (4.8%) 1 (3.8%) 0.990

Seborrheic keratosis 2 (9.5%) 1 (3.8%) 0.579

Lentigo 5 (23.8) 0 (0%) 0.013

Dermatitis 2 (9.5%) 1 (3.8%) 0.579

Pruritis 3 (14.3%) 4 (15.4%) 0.990

Vitiligo 0 (0%) 2 (7.7%) 0.495

Notalgia paresthetica 1 (4.8%) 1 (3.8%) 0.990

PEXG, pseudoexfoliative glaucoma; POAG, primary open-angle glaucoma
∗Significant P-value with Bonferroni adjustment is <0.005

mainly in their extremities. Although the frequency
of dry skin was almost twice in those with PEXG
compared to the POAG group, the difference failed
to reach the level of statistical significance (P =
0.130).

There was no significant difference in the
frequency of nevus and angiomas between the two
groups. However, lentigines were observed in five

PEXG patients, while none of the POAG patients
had this finding (P = 0.013).

In the subgroup analysis, there was no
association between gender or patients’ age
and the frequency of dermatologic manifestations
(P > 0.154 for all comparisons). Moreover, the
frequency of dermatologic findings was not

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Dermatological Manifestations in Glaucoma Patients; Ahmadpour et al

correlated with VA, IOP, or CDR (P > 0.142 for all
comparisons).

DISCUSSION

In this cross-sectional study, we reported the
frequency of skin manifestations in patients with
PEXG and POAG. Interestingly, all included PEXG
patients and most (92.3%) POAG subjects had at
least one dermatologic finding.

Glaucoma is the most common cause of
preventable, irreversible blindness in the world.[16]
With a prevalence of 1–5%, it was estimated that
almost 80 million people would be affected
by glaucoma in 2020.[17] Considering the
prevalence of the disease and its significant
health impact, investigation of the full range
of clinical manifestations of the disease and
its comorbidities, including skin manifestations,
seems to be highly relevant.[18]

While POAG is the most common form of the
disease, PEXG is the most common secondary
type of glaucoma.[19] PEXS is a multi-organ
systemic disease characterized by generalized
microfibrillopathy.[20] A mutation in the lysyl
oxidase-like-1 (LOXL1) gene can be a culprit initial
event;[21] however, different environmental factors,
including biological stress and free radicals,
infectious agents, and trauma, can initiate the
disease process.[22–25] In addition to glaucoma,
PEXS has a wide range of systemic comorbidities,
including but not limited to cardiovascular disease,
cerebrovascular disease, Alzheimer’s disease,
and sensorineural hearing loss.[26–29] Moreover,
precipitation of pseudoexfoliative materials has
been shown in different organ systems, including
viscera, blood vessels, skin, and ocular tissues.[1, 30]

Pseudoexfoliative material is a highly cross-
linked glycoprotein-proteoglycan complex, mainly
composed of elastic microfibrillar components,
such as fibrillin-1 and latent transforming growth
factor binding proteins (LTBP), as well as
chaperone molecules, such as clusterin, and
cross-linking enzymes, such as LOXL1 protein.[31]
In some reports, these materials were shown
to possess amyloid or amyloid-like features.[32]
In 1993, Schlötzer-Schrehardt and colleagues
examined eyelid skin biopsy specimens of 12
PEXS patients. They found pseudoexfoliative
material accumulations in the specimen of seven
patients, which was confirmed by electron

microscopy and immunological markers.[33]
Their findings are in line with other reports that
found pseudoexfoliative materials in extraocular
structures such as rectus and oblique muscles,
vortex vein, optic nerve sheath, and the skin
of the lateral canthus.[34]Their findings provide
first-hand data on dermatological involvement
in PEXS. Despite these clinicopathological
correlations, there is no published study on
clinical dermatological findings in PEXG patients.
Through the current research we are reporting a
broad group of skin disorders in these patients;
our findings can further support the possible
association between PEXS and skin disorders.

We observed a high prevalence of skin
manifestations in all glaucoma patients in the
present study. The most common dermatological
manifestations in both groups were seborrheic
dermatitis, dry skin, and cherry angioma. Erb et
al reported skin diseases, including dry skin, as
one of the most common comorbidities seen
in all glaucoma patients.[13] Their results are in
line with our findings; however, they did not
describe multiple types of skin lesions in their
study. In addition, skin reactions were described
in association with the use of anti-glaucoma eye
drops.[14] There was no significant difference
between our study groups in terms of glaucoma
severity and management; however, we excluded
patients with apparent allergic dermatitis from
topical glaucoma medication, as investigating the
possible role of topical medications was beyond
the scope of this study with its cross-sectional
design.

Seborrheic dermatitis was the most common
dermatological finding in both PEXG and POAG
patients. Several studies reported a prevalence
of 1–15% for seborrheic dermatitis in the general
population,[35–37] which is much lower than the
observed frequency (57.1–61.5%) in our patients.
This difference in prevalence can be either due to
an association between the seborrheic dermatitis
and glaucoma or the presence of dermatological
issues due to lower hygiene and skincare in
glaucoma patients. There is evidence that
patients with advanced glaucoma may have poorer
socioeconomic conditions than those with mild
glaucoma.[38] As a counterhypothesis, glaucoma
may be secondary to primary dermatological
disease. Of note, glaucoma has also been reported
following the use of topical corticosteroids
to treat eyelid dermatitis, such as seborrheic

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Dermatological Manifestations in Glaucoma Patients; Ahmadpour et al

and atopic dermatitis.[39] The eyelid’s chronic
inflammatory processes like seborrheic dermatitis
and meibomian gland dysfunction may also lead
to glaucoma. It has been proposed that regular lid
hygiene could prevent or treat glaucoma.[40]

Our study had several limitations. As this
was a cross-sectional study, we could only
report on possible associations, and no causal
relationship could be speculated based on our
findings. Moreover, we had a limited sample
size. Indeed, the lack of statistical significance in
many comparisons could be merely because of
insufficient statistical power. For example, twice
higher frequency of dry skin in PEXG patients
than in POAG patients did not reach statistical
significance; on the other hand, although PEXG
patients were almost a decade older than POAG
patients, we did not find any effect of age on
the frequency of skin manifestations. One can
acceptably argue that the higher frequency of
dry skin in PEXG was because they were older,
and we ’failed’ to demonstrate the effect of age
on this association. However, in the subgroup
analysis, we had the same number of elderly
subjects in both groups, which can decrease the
effect of age on the observed difference in the
frequency of dry skin. Finally, we did not have
a healthy control group with matched age, sex,
and socioeconomic status, which was a major
study limitation. Presence of that group could
further help to clarify the possible association
of dermatological findings with glaucoma versus
other confounding factors like age, job, and
socioeconomic condition.

Despite these limitations, to the best of our
knowledge, the current study is the first one that
investigated the dermatologic manifestations
in glaucoma patients. Future studies with
larger sample sizes, more diverse glaucoma
patients, and a healthy control group can
shed light on this less investigated aspect of
glaucoma.

In summary, we noticed a wide range of
dermatologic findings in POAG and PEXG
patients. We recommend ophthalmologists
and dermatologists to collaborate by referring
these types of patients to each other for more
comprehensive evaluation and management
of such possible comorbidies. This can help
diagnose and treat glaucoma patients earlier and
shift the focus from a merely ocular condition to a
multi-system disorder.

Acknowledgments

The authors would like to thank Dr Saeed Shkoohi
Rad (Associate Professor of Ophthalmology,
Mashhad University of Medical Sciences) for
helping with recruiting eligible patients.

Financial Support and Sponsorship

The study was supported by a research grant (No.
941297) from the Vice-Chancellor of Research at
Mashhad University of Medical Sciences.

Conflicts of Interest

The authors declare no potential conflicts of
interest for this article’s research, authorship, and
publication.

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