Pavlovskyi M. Optimization of the dry eye syndrome diagnosis in patients with hypothyroidism by cytological and biochemical changes in the ocular surface tissues (experimental and clinical study)

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number


Applicant for


  • 14.01.18 - Очні хвороби


Specialized Academic Board

Д 41.556.01

State Institution "The Filatov Institute of Eye Disease and Tissue Therapy of NAMS of Ukraine"


Object: dry eye syndrome. Purpose: to optimize the diagnosis of dry eye syndrome in hypothyroidism based on the study of cytological features and biochemical disorders in the bulbar conjunctiva, cornea and tear fluid (experimental-clinical study). Methods: general ophthalmological; special ophthalmological: determination of lacrimal production by Schirmer test, tear film rupture time by Norn test, corneal and conjunctival staining with fluorescein, LIPCOF test, ocular surface disease index (OSDI); cytological; biochemical (evaluation of lipid peroxidation (LPO) by the level of malonic dialdehyde (MDA) and diene conjugates (DC)); the level of oxidized and reduced glutathione; state of redox processes on the activity of enzymes lactate dehydrogenase (LDH), malate dehydrogenase (MDH); the state of lysosomal membranes by the activity of free and bound forms of the enzyme acidic phosphatase by spectrophotometry; statistical. DES is found in 39.5% of patients with primary hypothyroidism, among them, mild stage of DES is found in 23%, moderate stage – in 48.3% and severe stage – in 28.7% of patients. Differences between clinical manifestations of DES in patients with subclinical and manifest hypothyroidism have been established. The degree of clinikal signs, such as the discomfort in the eyeball area, degenerative changes in the conjunctival epithelium (fluorescein staining), the presence of inclusions in the tear film, are significantly higher in the manifest form of hypothyroidism. The tear film stability and tear production (test Shirmer I) are lower in the manifest form of hypothyroidism compared with subclinical: 6.1 (SD 5.4) mm and 5.04 (SD 2.0) s.; 9.4 (SD 5.9) mm and 5.84 (SD 2.2) s., respectively. The severe degree of DES was more commonly observed in manifest hypothyroidism (54.1%) compared with subclinical (10.0%) (χ2=20,22; р=0,00004). In patients with hypothyroidism and DES the impression cytology of the bulbar conjunctiva revealed: dystrophy and metaplasia of epithelial cells, decreased number of goblet cells. The described changes were more pronounced in patients with manifest form of hypothyroidism. In experimental hypothyroidism in rat’s conjunctival epithelium, cornea and tear the state of redox processes is disturbed, which manifested as: reduced activity of lactate dehydrogenase (LDG) and malate dehydrogenase (MDG) in the severe stage of hypothyroidism in cornea (by 29.2% and 23.7%) and conjunctiva (by 34.7% and 28.7% respectively), indicating a decreased intensity of redox processes; as well as increased activity of lactate dehydrogenase and malate dehydrogenase in the tear (by 40.1% and 24.6% respectively), which indicates destruction of the epithelium; increased concentrations of malondialdehyde and diene conjugates in the cornea (by 51.3% and 25.4%), conjunctiva (by 85.6% and 55.6%) and tear (by 101.3% and 31,2% respectively), especially in the severe stage, which indicates the activation of peroxidation processes. The concentration of reduced glutathione was decreased in the cornea and tear, indicating antioxidant reserves reduction; increased activity of acid phosphatase in the cornea (by 20.5% and by 28.1%) and tear (by 23.3% and by 39.8%) in the initial and severe stages, respectively, indicating destabilization of the epithelial cells’ lysosomes. The degree of enhancement of enzyme activity depends on the stage of the disease and is more pronounced in the later stage of the process. In the tear of patients with DES and hypothyroidism the most pronounced disorders of redox processes and stability of lysosome membranes were found in manifest disease: the activity of LDG and MDG in the manifest form increased by 64.1% and 30.9%, and in the subclinical form – by 15.7% and 28.4%, respectively, compared with patients with hypothyroidism without DES. In manifest form of hypothyroidism lactate dehydrogenase activity was 23.5% higher than in patients with subclinical hypothyroidism, which indicates that the membrane integrity of the epithelial cells is impaired; the level of malondialdehyde increased by 17.7% in subclinical and 32.2% in manifest forms of the disease, compared with patients with hypothyroidism without DES, which indicates increased lipid peroxidation in the eye surface tissues. In the tear of patients with hypothyroidism and DES the activity of acid phosphatase is increased, which indicates the damage of epithelium lysosomes. In subclinical form, it increased by 39% and in manifest form by 45.5%, in comparison with healthy patients, but did not differ significantly in patients with hypothyroidism without DES. The results of the work were introduced in the practical work of the SI "Filatov institute of eye diseases and tissue therapy of the NAMS of Ukraine”, LRC CNE "Lviv Regional State Clinical Treatment and Diagnostic Endocrinology Center" and ophthalmology department of LRC CNE "Lviv Regional Clinical Hospital". Scope - medicine, ophthalmology.


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