The Choice of Dry Eye Therapy Depending on Ocular Surface Condition

Purpose: to develop approaches to differentiated substitution therapy in patients with dry eye (DE) of mild and moderate severity.

Patients and methods. We examined 86 DE patients (22–45 years old; 38 men, 48 women). Group-1 included 54 patients (54 eyes) with mild DE under conditions of combined lipid-mucose-deficiency, group-2 32 patients (32 eyes) with moderate DE against the background of combined lipid-aqua-mucose-deficiency. Conducted: DE symptoms registration (OSDI scale); Norn and Shirmer-1 tests; OCT meniscometry; assessment of the Bijsterveld xerosis index and ‘lid-vipers’ symptom identification; Norn’s compression test. To assessment the therapy effectiveness, patients in both groups were divided into subgroups. Patients of subgroup 1.1 (18 eyes) carried out ‘fat-water’ type emulsion instillations, subgroup 1.2 (18 eyes) — 0.15 % sodium hyaluronate instillation (Hylabak®), subgroup 1.3 (18 eyes) — 3.0 % trehalose (Thealoz®) — 1–2 drops, 4 times a day. All persons included in group-1 were additionally recommended to apply 5.0 % dexpanthenol gel at night. Patients of subgroup 2.1 (16 eyes) received 0.15 % sodium hyaluronate instillation (Hylabak®), patients of subgroup 2.2 (16 eyes) 0.15 % sodium hyaluronate (Hylabak®) and 3.0 % trehalose (Thealoz®) instillation — 4 times a day. All patients included in group-2 were additionally recommended to apply ointment with vitamin A at night. The main criterion for the therapy effectiveness was the tear film brake up time (TBUT, s) two months after the start treatment. Statistical processing included: calculation the mean and its standard deviation (M ± s); assessment of the significance of differences (Wilcoxon’s t-test, KruskalWallis test, Mann-Whitney U-test).

Results. In group-1 patients the following TBUT dynamics was recorded: in subgroup 1.1 — from 5.4 ± 0.5 to 6.2 ± 0.6 s (p < 0.05); in subgroup 1.2 — from 5.2 ± 0.4 to 6.6 ± 0.6 s (p < 0.05); in subgroup 1.3 — from 5.3 ± 0.5 to 7.1 ± 0.7 s (p < 0.05). The most pronounced TBUT increase was noted in subgroup 1.3 (trehalose instillation). In group-2, the increase in TBUT was: in subgroup 2.1 — from 3.5 ± 0.3 to 4.7 ± 0.3 s (p < 0.05); in subgroup 2.2 — from 3.4 ± 0.2 to 5.2 ± 0.4 s (p < 0.05). A significantly more pronounced TBUT increase was noted in subgroup 2.2 (sodium hyaluronate and trehalose instillation).

Conclusion. In our opinion, differentiated approaches to DE replacement therapy may be included: for mild DE in conditions of lipid-mucose-deficiency — instillation of bioprotector based on 3.0 % trehalose (Thealose®); in case of moderate DE against the background of lipid-aqua-mucose-deficiency — 0.15 % sodium hyaluronate (Hylabak®) instillation in combination with a bioprotector based on 3.0 % trehalose (Thealoz®). 

1. Craig J.P., Nelson J.D., Azar D.T., Belmonte C., Bron A.J., Chauhan S.K., de Paiva C.S., Gomes J.A.P., Hammit K.M., Jones L., Nichols J.J., Nichols J.S., Novak G.D., Stapleton F., Wilcox M.D.P., Wolffsohn J.S., Sullivan TFOS DEWS II Report Executive Summary. The Ocular Surface: 2017;XXX:1–11. DOI: 10.1016/j.jtos.2017.08.003

2. Stapleton F., Optom M.C., Alves M., Bunya V.Y., Jalbert I., Lekhanont K., Malet F., Na Kyung-Sun, Schaumberg D., Ushino M., Vehof J., Viso E., Vitale S., Jones L., Optom F.C. TFOS DEWS II Epidemiology Report. The Ocular Surface. 2017;15:334– 365. DOI: 10.1016/j.jtos.2017.05.003

3. Brzhesky V.V., Egorova G.B., Egorov E.A. Dry eye and ocular surface diseases. Moscow: GEOTARMedia; 2016. 448 p. (In Russ.).

4. Baudouine C., Messmer E., Aragona P., Geerling G., Akova Y.A., Benitez-delCastilio J., Boboridis K.G., Merayo-Lloves J., Rolando M., Labetoulle Revisiting the vicious circle of the dry eye disease: focus on the pathophysiology of meibomian gland dysfunction. Br. J. Ophthalmol. 2016;100(3):300–306. DOI: 10.1136/bjophthalmol-2015-307415

5. Sakhnov S.N., Yanchenko S.V., Malyshev A.V. Dry eye epidemiology in patients before refractive operations. Ophthalmology in Russia = Oftalmologiya. 2018:15(1):92–101 (In Russ.). DOI: 10.18008/1816-5095-2018-1-92-101

6. Sakhnov S.N., Yanchenko S.V., Malyshev A.V. Dry eye epidemiology in patients before cataract surgery. Ophthalmology in Russia = Oftalmologia. 2020;17(2):281–289 (In Russ.). DOI: 10/18008/1816-5095-2020-2-281-289

7. Donnenfeld E. Dry eye after LASIK. Cataract & Refractive Surgery Today. 2011;5:31–33.

8. Shtein R.M. Post-LASIK dry eye. Expert. Rev. Ophtalmol. 2011;6(5):575–582. DOI: 10.1586/eop.11.56

9. Shoja M.R., Besharati M.R. Dry eye after LASIK for myopia: incidence and risk factors European Journal of Ophthalmology. 2007;17(1):1–6. DOI: 10.1177/112067210701700101

10. Berk T.A., Schlenker M.B., Campos-Moller X., Pereira A.M., Ahmed I.K. Visual and refractive outcomes in manual versus femtosecond laser-assisted cataract surgery: a single-centre retrospective cohort analysis of 1838 eyes. Ophthalmology. 2018:6. PII: S0161-6420(17)33311-0:1172–1180. DOI: 10.1016/j.ophtha.2018.01.028

11. Guo N., Puhlev D., Brown D.R., Mansbridge J., Levine F. Trehalose expression confers desiccation tolerance in human cells. Nature Biotechnology. 2000;18(2):168– 171. DOI: 10.1038/72616

12. Hill-Bator A., Misiuk-HojBo M., Marycz K., Crzesiak J. Trehalose-based eye drops preserve viability and functionality of cultured human corneal epithelial cells during desiccation. Hindawi Publishing Corporation BioMed. 2014;Article ID 292139. DOI: 10.1155/2014/292139

13. Matsuo T. Trehalose protects corneal epithelial cells from death by drying. Br.J.Ophth. 2001;85(5):610–612. DOI: 10.1136/bjo.85.5.610

14. Shpak A.A. Issues of the statistical analysis in the Russian ophthalmic journals. The Fyodorov Journal of Ophthalmic Surgery = Oftalmohirurgiya. 2016;1:73–77 (In Russ.). DOI: 10.25276/0235-4160-2016-1-73-77

15. Bijesterveld O.P. Diagnostic tests in the sicca syndrome. Arch. Ophthalmol. 1969;82:10–14. DOI: 10.1001/archopht.1969.00990020012003

16. Korb D.R. The tear film — its role today and in future. In The Tear Film, structure, function and examination. Butterworth — Heimann. 2002. 254 p.

17. Nichols K.N., Foulks G.N., Bron A.J., Glasgow B.J., Dogru M., Tsubota K., Lemp M.A., Sullivan D.A. The International Workshop on Meibomian Gland Dysfunction: Executive Summary IOVS, Special Issue. 2011;52(4):1923–1929. DOI: 10.1167/iovs.10-6997a

18. Sakhnov S.N., Yanchenko S.V., Malyshev A.V. Optimization of therapy for dry eye syndrome in patients before refractive interventions. Russian ophthalmological journal = Rossiyskiy oftal’mologicheskiy zhurnal. 2018;11(4):87–94 (In Russ.). DOI: 10.21516/20720076-2018-11-4-87-94

19. Guillon M., Maissa C., Wong S. Symptomatic relief associated with eyelid hygiene in anterior blepharitis and MGD. Eye and contact lens. 2012;38(5):306–312. DOI: 10.1097/ICL.0b013e3182658699

20. Peral A., Alonso J., Garsia-Garsia C., Nino-Rueda C., Calvo del Bosque P. Importance of lid hygiene before ocular surgery: qualitative and quantitative analysis of eyelid and conjunctiva microbiota. Eye and contact lens. 2016;42(6):366–370. DOI: 10.1097/ICL.0000000000000221

21. Yanchenko S.V., Malyshev A.V., Sakhnov S.N., Fedotova N.V., Orehova O.Y. Eye lid hygiene in chronic allergic blepharoconjunctivitis patients before laser refractive surgery. Annals of Ophthalmology = Vestnik oftal’mologii. 2016;5:83–88 (In Russ.). DOI: 10.17116/oftalma2016325