Pseudoexfoliation syndrome and meibomian gland dysfunction

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Pseudoexfoliation syndrome (PEX) is a relatively widespread generalized age-related disease of connective tissue. The condition of meibomian glands in patients with PEX was not evaluated yet. Aim. To evaluate the condition of meibomian glands in PEX. Methods. Overall, 132 eyes of 66 patients with PEX syndrome and 128 eyes of 64 patients without it were enrolled in this prospective study. Results. The signs of atonic changes in meibomian glands were similar in both groups. Meibomian glands dysfunction was significantly more expressed in patients with PEX (p < 0,05).

Pseudoexfoliation syndrome (PEX) is a local manifestation of a systemic disease characterized by the production and accumulation of pathological extracellular material on the intra- and extraocular structures. Thus, pseudoexfoliation material (PEM) accumulation has been found in the heart, lungs, kidneys, liver, gall bladder, and cerebral arteries [31, 32]. An association between PEX and cardio-cerebrovascular diseases was identified [7, 20, 27, 28]. According to the literature, PEX is most common in the Scandinavian countries, where it reaches 40.6% among patients older than 80 years [6, 15]. The lowest prevalence is observed in Australia [21] and in Asian countries [13, 16, 22]. The prevalence of PEX increases with age [6, 13, 15, 16, 21, 22].

A characteristic manifestation of PEX is the accumulation of white–gray flocculent material on the ocular structures of the anterior segment, mainly on the anterior capsule of the lens and on the pupillary border [1, 18, 24]. PEM was detected on the epithelium of the ciliary body, the corneal endothelium, and the trabecular meshwork, as well as in the tissues of the iris. The development of glaucoma, cataract, and spontaneous subluxation of the lens and the increased risk of intra- and postoperative complications of cataract surgery in PEX are associated with the involvement of these structures [9, 25, 26, 29-31].

With the use of electron microscopy and specific immunohistochemical markers, the accumulation of PEM in the conjunctiva was revealed [11, 12, 25]. According to H. Erdogan et al., it is the involvement of the conjunctiva that underlies the destruction of the ocular surface tissues in PEX [12].

PEX adversely affects the condition of the ocular surface tissues, which has been previously demonstrated in several studies [3, 5, 12, 19]. The tear film break-up time, evaluation of tear production, and severity of conjunctivochalasis were used as the main indicators of disease in these studies [3, 5, 12, 19]. We additionally analyzed the state of the conjunctival epithelium, the degree of conjunctivochalasis, and the index of damage to the eye surface. According to the data obtained, in PEX there is damage to the epithelium of the conjunctiva, advanced conjunctivochalasis, and the symptom complex of severe dry eye syndrome (DES) [5].

Subclinical chronic inflammation is common in DES and PEX [10]. In PEX, this is demonstrated by an increase in the content of oxidative stress markers and a decrease in the content of antioxidants in the anterior chamber [17]. Chronically occurring inflammation in PEX is likely to be associated with an increase in the concentration of free radicals in these tissues.

The ocular adnexa plays an important role in protecting the tissues of the ocular surface and providing clear vision [2, 4, 23]. The function of the meibomian glands in PEX has not been previously studied. Meibomian gland dysfunction leads to tear film instability, and excessive evaporation of tears; consequently, this aggravates damage to the ocular surface tissues.

The aim of our study was to assess the presence and extent of meibomian gland dysfunction in patients with PEX.


The study included 260 eyes of 130 patients admitted for the surgical treatment of cataracts in the Microsurgical department No. 5 of the City general hospital No. 2 from September 2015 to March 2016. The patients were divided into 2 groups. The study group consisted of 66 patients (132 eyelids) with clinically confirmed PEX, while the control group consisted of 64 patients (128 eyelids) without PEX. PEX was considered clinically confirmed when pseudoexfoliation material was detected on the anterior capsule of the lens or on the pupillary border.

The groups were equal in terms of sex and age (Table 1).


Table 1. Distribution of patients according to gender and age in studied groups (%, abs., n is the number of patients)

Таблица 1. Распределение пациентов по полу и возрасту в группах исследования (%, абс., n – количество пациентов)


Study group, n = 66

Control group, n = 64

Difference significance, р


75,95 ± 1,62

73,78 ± 2,12

> 0,05



12 (18,2%)

14 (21,9%)

> 0,05


54 (81,8%)

50 (78,1%)


The exclusion criteria were the presence of diseases leading to secondary meibomian dysfunction, including acne rosacea, atopic dermatitis, ocular cicatricial pemphigoid, Stevens–Johnson syndrome, and eyelid malposition.

All patients underwent the standard ophthalmologic examination and meibomian gland evaluation.

The indicators of the state of meibomian glands were divided into several groups and evaluated on a grading system in accordance with the recommendations of the International Workshop on Meibomian Gland Dysfunction (2011; Table 2).


Table 2. Grading of meibomian gland dysfunction (in accordance with The International Workshop on Meibomian Gland Dysfunction, 2011)

Таблица 2. Балльная система оценки дисфункции мейбомиевых желёз (в соответствии с The International Workshop on Meibomian Gland Dysfunction, 2011)



I. Eyelid margin

Thickness of the lower eyelid margin, mm


Rounding of the posterior margin of the eyelid: +/–


Telangiectasia of the eyelid margin: +/–


The eyelid margin roughness: +/–


Eyelid malposition


Deplumation: +/–


Trichiasis/distichiasis: +/–


Anterior blepharitis: +/–


Mucocutaneous junction of the eyelid margin *:

а) forward shift +/–;

b) backward shift +/–;

с) junction irregularity +/–




II. Number of functioning meibomian glands (among 8 central)

0, all glands function; 1, 3–4 glands function; 2, 1–2 glands function; 3, no glands function


III. Condition of the orifices of meibomian glands

А. Pouting or plugging

B. Narrowed

С. Duct cicatrisation

D. Displaced backwards

Е. Vascularized






Width of the excretory ducts

1 — < 1 mm, 2 — ≥ 1–2 mm, 3 — ≥2 mm


IV. Characteristics of the discharge of meibomian glands

Quality of the discharge:

0, clear; 1, opaque; 2, granular; 3, congested


Quality: (0, clear; 1, cloudy; 2, granular; 3, toothpaste)


Expressibility: (1, light; 2, moderate; 3, heavy pressure)


* Normally, the mucocutaneous junction is located at the border of 2/3 of the anterior margin and the posterior margin of the 1/3 of the eyelid (The International Workshop on Meibomian Gland Dysfunction: Report of the Diagnosis Subcomittee, IOVS, Special Issue, 2011, Vol. 52, No 4


Statistical processing of data was performed using SPSS Statistics v22.0. The main statistical parameters were mean values, standard deviations, medians, and minimum and maximum values. The ratio of quantitative variables in two independent groups was estimated using a t-test. In conditions where p < 0.05, the differences were considered statistically significant. The statistical significance of the differences between the groups in terms of qualitative indicators was estimated using cross tables and Pearson’s χ2 test.


The assessment parameters of the state of meibomian glands were divided into 4 main sections.

In the first section, the state of the lower eyelid margin was studied (Table 3). The main evaluation indices were the thickness of the margin, rounding or roughness of the margin, presence of telangiectasias, malposition of the lower eyelid, and projection of the mucocutaneous junction.


Table 3. Assessment of condition of meibomian glands in the studied group (n, number of eyes)

Таблица 3. Оценка состояния мейбомиевых желёз в исследуемых группах (n — количество глаз)


Mean value in the study group, n = 132

Mean value in the control group, n = 128

Difference significance, р

Eyelid margin state, score

7.86 ± 0.24

5.52 ± 0.29

< 0.05

Number of functioning meibomian glands (of 8 central)

3.33 ± 0.25

5.30 ± 0.26

< 0.05

Condition of the excretory ducts, score

3.0 ± 0.16

2.77 ± 0.12

> 0.05

Characteristics of the discharge of meibomian glands, score

3.17 ± 0.23

1.5 ± 0.1

< 0.05


In patients of both groups, the eyelid margin was altered, but in the study group, the changes were significantly more prevalent (p < 0.05). The average thickness of the lower eyelid margin in the study group was 3.41 ± 0.08 mm, while in the control group it was 2.61 ± 0.09 mm (p < 0.05). Rounding and roughness of the eyelid margin was seen in the majority of patients of both groups (p > 0.05). Trichiasis and distichiasis were observed in some cases (p > 0.05). The incidence of anterior blepharitis was not significantly different: in the study group, it was seen in 37.9% of patients, while in the control group it was noted in 32.8% (p > 0.05). The mucocutaneous junction was displaced forward in majority of patients in both groups (p > 0.05).

The second section was devoted to calculating the number of functioning meibomian glands (see Table 3). For patients of the older age group, a decrease in the number of functioning meibomian glands is characteristic. A significantly greater decrease was observed in the patients of the study group: 3.33 ± 0.25 in patients with PEХ and 5.30 ± 0.26 in patients without PEХ (p < 0.05).

The main aim of the third section was to study the excretory ducts state of the meibomian glands (see Table 3). Narrowing of the excretory ducts was noted in 72.4% patients in the study group and in 90.6% in the control group (p < 0.05). The excretory ducts were predominantly displaced backwards in 57.6% patients in the study group and 61.7% in the control group, which is likely due to the characteristic forward shift of the mucocutaneous junction in patients of the older age group (p > 0.05).

The fourth section included the study of meibomian gland discharge (see Table 3). The defined indicators were the quality of the discharge, the presence of foamy discharge, and the necessary force required to express contents of the meibomian glands. Secretion of glands decreases with age, but with meibomian dysfunction, an increase in viscosity and loss of transparency of the discharge is observed. An opaque content of meibomian glands was found in 72.7% patients in the study group and in 23.4% in the control group (p < 0.05). For expressing the contents of the meibomian glands in the study group, a moderate compression force was required; in the control group, a weak force was required (p < 0.05). Foamy discharge was observed in single cases (p > 0.05).

Thus, in patients of both groups, involutional changes in meibomian glands were observed, such as thickening, roughness, rounding of the lower eyelid margin, forward shifting of the mucocutaneous junction, narrowing of the excretory ducts of meibomian glands, and reduction in the number of functioning glands. Nevertheless, in patients with PEХ, most of the changes were significantly more prevalent.

The main manifestations of dysfunction of meibomian glands include obstruction of the duct and the presence of an opaque and viscous discharge [8]. In 72.7% of patients with PEХ, an opaque discharge was observed, whereas it was observed in only 23.4% patients without PEХ (p < 0.05). The obstruction of the ducts was determined by the force necessary for expressing contents of the meibomian glands. In the study group, 72.7% patients required a moderate squeezing force, while in 67.9% of patients in the control group the force required was weak, which indicates a more pronounced obstruction in the study group patients.


PEХ undoubtedly affects ocular adnexa. PEM has been found in conjunctiva, orbital septum, and connective tissues of the orbit and extraocular muscles [12, 19, 25].

Meibomian glands play an important role in ensuring stability of the tear film as well as preventing damage to the ocular surface tissues. Meibomian glands are subject to age-related changes. The main involutional changes are hyperkeratosis, rounding, roughness, eyelid margin vascularization, and mucocutaneous junction displacement [2, 14]. The main manifestations of meibomian gland dysfunction include a decrease in the number of functioning glands, obstruction or atrophy of the ducts, and an opaque and/or congestive nature of the discharge.

According to the data obtained, the involutional changes were equally prevalent in patients of both groups, whereas manifestations of meibomian gland dysfunction (MGD) were significantly more pronounced in patients with PEХ. Thus, a clinical association between MGD and PEХ is identified. However, exact mechanisms of the interaction are unknown.

Previously, we found a clinical association between PEХ and an atonic change in the supporting structures of the ocular adnexa [12]. Thus, atony of the Riolan muscle, which surrounds the excretory ducts of meibomian glands, is one of the possible mechanisms for MGD development in PEX.

Another cause of MGD development in PEX is a characteristic forward shift of the mucocutaneous junction, which leads to a decrease in the area of the lipid-moistened skin and an increase in the area of the water-moistened mucous membrane; accordingly, there is an instability of the tear film due to increased tears evaporation. The latter causes an increase in tear film osmolarity; this leads to a decrease in the number of goblet cells. This further aggravates the damage to the ocular surface tissues, which takes place during MGD.

The potential causal relationship and the clinical significance of this association should be studied in more detail. Patients with PEX require more thorough examination and observation of both ocular tissue involvement as well as ocular adnexa involvement.

Vitaly V Potemkin

Author for correspondence.
FSBEI HE I.P. Pavlov SPbSMU MOH Russia
Russian Federation

PhD, assistant professor. Department of Ophthalmology

Elena V Ageeva
FSBEI HE I.P. Pavlov SPbSMU MOH Russia
Russian Federation

resident. Department of Ophthalmology

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