Dry eye disease in keratoconus: etiology and medical treatment
DOI: 10.32364/2311-7729-2022-22-2-122-126
V.V. Averich
Scientific Research Institute of Eye Diseases, Moscow, Russian Federation
This paper reviews published data on the studies on keratoconus associated with dry eye disease (DED) presentations. Despite the lack of a direct correlation between DED and keratoconus, many studies have demonstrated that keratoconus is associated with DED in more than 80% of cases. The author describes major endogenous and exogenous (inflammatory, immune/allergic, mechanical, neuropathic) factors triggering the development and association of these conditions. Approaches to the medical treatment of disorders resulting from the association of these entities are discussed. The primary management strategy implies tear film and ocular surface protection with tear substitutes based on the sodium salt of hyaluronic acid. In the lack of the effect of tear substitutes or in rigid gas permeable contact lens wearers, gel-based dexpanthenol in high concentrations is recommended. This treatment significantly increases drug bioavailability and prolongs the ocular surface reparation. Scleral contact lenses ensuring intact corneal epithelium and high visual acuity in irregular astigmatism caused by keratoconus are also used for corneal protection and DED therapy.
Keywords: keratoconus, keratectasia, dry eye disease, epitheliopathy, tear film.
For citation: Averich V.V. Dry eye disease in keratoconus: etiology and medical treatment. Russian Journal of Clinical Ophthalmology. 2022;22(2):122–126 (in Russ.). DOI: 10.32364/2311-7729-2022-22-2-122-126.
About the author:
Veronika V. Averich — C. Sc. (Med.), junior researcher of the Division of Refractive Disorders, Scientific Research Institute of Eye Diseases; 11A, B, Rossolimo str., Moscow, 119021, Russian Federation; ORCID iD 0000-0001-5778-4123.
Contact information: Veronika V. Averich, e-mail: veronikky@mail.ru.
Financial Disclosure: the author has no a financial or property interest in any material or method mentioned.
There is no conflict of interests.
Received 02.03.2022.
Revised 29.03.2022.
Accepted 21.04.2022.
References
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11. Solomon A., Dursun D., Liu Z. et al. Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease. Invest Ophthalmol Vis Sci. 2001;42(10):2283–2292.
12. Perez V.L., Stern M.E., Pflugfelder S.C. Inflammatory basis for dry eye disease flares. Exp Eye Res. 2020;201:108294. DOI: 10.1016/j.exer.2020.108294.
13. Brzhesky V.V., Egorova G.B., Egorov E.A. Dry eye syndrome and ocular surface diseases: clinic, diagnosis, treatment. Moscow: GEOTAR-Media; 2016 (in Russ.).
14. Dogru M., Karakaya H., Ozçetin H. et al. Tear function and ocular surface changes in keratoconus. Ophthalmology. 2003;110(6):1110–1118. DOI: 10.1016/S0161-6420(03)00261-6.
15. Harrison R.J., Klouda P.T., Easty D.L. et al. Association between keratoconus and atopy. Br J Ophthalmol. 1989;73(10):816–822. DOI: 10.1136/bjo.73.10.816.
16. Rahi A., Davies P., Ruben M. et al. Keratoconus and coexisting atopic disease. Br J Ophthalmol. 1977;61(12):761–764. DOI: 10.1136/bjo.61.12.761.
17. Khor W.B., Wei R.H., Lim L. et al. Keratoconus in Asians: demographics, clinical characteristics and visual function in a hospital-based population. Clin Exp Ophthalmol. 2011;39(4):299–307. DOI: 10.1111/j.1442-9071.2010.02458.x.
18. Owens H., Gamble G. A profile of keratoconus in New Zealand. Cornea. 2003;22(2):122–125. DOI: 10.1097/00003226-200303000-00008.
19. Mostovoy D., Vinker S., Mimouni M. et al. The association of keratoconus with blepharitis. Clin Exp Optom. 2018;101(3):339–344. DOI: 10.1111/cxo.12643.
20. Pinto R.D.P., Abe R.Y., Gomes F.C. et al. Meibomian gland dysfunction and dry eye in keratoconus. Arq Bras Oftalmol. 2021:S0004–27492021005008209. (Online ahead of print.) DOI: 10.5935/0004-2749.20220056.
21. Feizi S., Javadi M.A., Alemzadeh-Ansari M. et al. Management of corneal complications in vernal keratoconjunctivitis: A review. Ocul Surf. 2021;19:282–289. DOI: 10.1016/j.jtos.2020.10.005.
22. Dienes L., Kiss H.J., Perényi K. et al. corneal sensitivity and dry eye symptoms in patients with keratoconus. PLoS One. 2015;10(10):e0141621. DOI: 10.1371/journal.pone.0141621.
23. Bubnova I., Surnina Z., Averich V., Sarkisova K. Effect of corneal collagen crosslinking on the corneal structure in keratoconus. Vestnik Oftalmologii. 2020;136(5):268–276 (in Russ.). DOI: 10.17116/oftalma2020136052268.
24. Avetisov S.E., Bubnova I.A., Surnina Z.V. et al. Changes in cornea structure after corneal collagen crosslinking in keratoconus. Meditsinskiy Sovet. 2022;16(6):226–233 (in Russ.). DOI: 10.21518/2079-701X-2022-16-6-226-233.
25. Lema I., Durán J.A., Ruiz C. et al. Inflammatory response to contact lenses in patients with keratoconus compared with myopic subjects. Cornea. 2008;27(7):758–763. DOI: 10.1097/ICO.0b013e31816a3591.
26. López-de la Rosa A., González-García M.J., Calonge M., Enríquez-de-Salamanca A. Tear inflammatory molecules in contact lens wearers: a literature review. Curr Med Chem. 2020;27(4):523–548. DOI: 10.2174/0929867326666190409152921.
27. Mazzotta C., Raiskup F., Baiocchi S. et al. crosslinking results and literature overview. management of early progressive corneal ectasia: Springer; 2017: 33–62.
28. Bubnova I.A., Egorova G.B., Averich V.V., Mitichkina T.S. Medical treatment for dry eye in patients with keratoconus after corneal cross-linking. Russian Journal of Clinical Ophthalmology. 2020;20(2):67–71 (in Russ.). DOI: 10.32364/2311-7729-2020-20-2-67-71.
29. Voronin G.V., Bubnova I.A., Averich V.V., Sarkisova K.G. Precorneal tear film after corneal collagen cross-linking in keratoconus (preliminary report). Vestnik Oftalmologii. 2021;137(5):224–230 (in Russ.). DOI: 10.17116/oftalma2021137052224.
30. Vastardis I., Gatzioufas Z., McLintock C. et al. Tear film parameters before and after intracorneal ring segment implantation in keratoconic eyes. Eur J Ophthalmol. 2021;31(5):2213–2218. DOI: 10.1177/1120672120958301.
31. Egorova G.B., Mitichkina T.S., Shamsudinova A.R. Corneal protection in contact lens users. Vestnik Oftalmologii. 2014;130(2):57–64 (in Russ.).
32. Aragona P., Papa V., Micali A. et al. Long term treatment with sodium hyaluronate — containing artificial tears reduces ocular surface damage in patients with dry eye. Br J Ophthalmol. 2002;86(2):181–184. DOI: 10.1136/bjo.86.2.181.
33. Johnson M.E., Murphy P.J., Boulton M. Effectiveness of sodium hyaluronate eyedrops in the treatment of dry eye. Graefes Arch Clin Exp Ophthalmol. 2006;244(1):109–112.
34. Nishida T., Nakamura M., Mishima H., Otori T. Hyaluronan stimulates corneal epithelial migration. Exp Eye Res. 1991;53:753–758. DOI: 10.1016/0014-4835(91)90110-z.
35. Egorova G.B., Fedorov A.A., Mitichkina T.S. et al. Influence of tear substitutes and corneoprotective therapy on a condition of ocular surface in patients with dry eye syndrome. Russian Journal of Clinical Ophthalmology. 2015;16(1):17–23 (in Russ.).
36. Jain S., Singh S., Nagar A. Brief communication: Dexpanthenol and its ophthalmic uses. J Clin Exp Ophthalmol. 2017;8(5):678. DOI: 10.4172/2155-9570.1000678.
37. Kobayashi D., Kusama M., Onda M., Nakahata N. The effect of pantothenic acid deficiency on keratinocyte proliferation and the synthesis of keratinocyte growth factor and collagen in fibroblasts. J Pharmacol Sci. 2011;115(2):230–234. DOI: 10.1254/jphs.10224sc.
38. Rybakova E.G., Egorova G.B., Kalinich N.I. Corneregel — new stimulator of reparative regeneration. Russian Journal of Clinical Ophthalmology. 2001;4:162 (in Russ.).
39. Wilson C.G., Zhu Y.P., Frier M. et al. Ocular contact time of a carbomer gel (GelTears) in humans. Br J Ophthalmol. 1998;82(10):1131–1134. DOI: 10.1136/bjo.82.10.1131.
40. Kukhtenko G.P., Popova T.V., Gladukh Ie.V., Kukhtenko A.S. Comparative analysis of carbomer polymers for pharmaceutical and cosmetic practice Zaporozhye medical journal. 2020;22(3):431–436 (in Russ.).
41. Anurova M.N., Bakhrushina E.O., Lapik I.V., Krechetov S.P. The determination of the rheological optimum of ophthalmic gels. Modern aspects of the ophthalmic dosage forms development. Drug development & registration. 2017;(4):64–70 (in Russ.).
42. Rajoria G. Gupta A. In-Situ Gelling System: A Novel Approach for Ocular Drug Delivery. Am J Pharm Tech Res. 2012;2(4):24–53.
43. Gross D., Tekster A. Report on biological assessment and clinical evaluation of the drug PARIN-POS. Edition 005. Translation from English and German. 2015 (in Russ.).
44. Egorova G.B., Mitichkina T.S., Shamsudinova A.R. Evaluation of Restasis usage in contact lens wearers with dry eye syndrome. Russian Journal of Clinical Ophthalmology. 2014;14(4):198–202 (in Russ.).
45. Shorter E., Harthan J., Nau A. et al. Dry eye symptoms in individuals with keratoconus wearing contact lenses. Eye Contact Lens. 2021;47(9):515–519. DOI: 10.1097/ICL.0000000000000802.
46. Fedotova K., Grabovetsky V.R., Novikov S.A., Ezugbaya M. Miniscleral lenses in the treatment of patients with dry eye syndrome (first own experience). Ophthalmology Journal. 2019;12(1):5–12 (in Russ.). DOI: 10.17816/OV1215-12.
47. Listratov S.V., Bakalova N.A., Averich V.V. OKVision® SMARTFIT™ scleral contact lens manufacturing technology. The EYE GLAZ. 2021;23(2):47–52 (in Russ.). DOI: 10.33791/2222-4408-2021-2-47-52.
2. Constantin M.M., Corbu C., Potop V. et al. Evaluation of Dry Eye Symptomatology at Patients with Keratoconus. Revista de Chimie. 2019;70(1):92–95. DOI: 10.37358/RC.19.1.6858.
3. Bubnova I.A., Averich V.V. Status of precorneal tear film in keratoconus Sovremennye tekhnologii v oftal’mologii. 2020;(4):319–320 (in Russ.). DOI: 10.25276/2312-4911-2020-4-319-320.
4. Carracedo G., Recchioni A., Alejandre-Alba N. et al. Signs and symptoms of dry eye in keratoconus patients: a pilot study. Curr Eye Res. 2015;40(11):1088–1094. DOI: 10.3109/02713683.2014.987871.
5. Rattan S.A., Anwar D.S. Comparison of corneal epithelial thickness profile in dry eye patients, keratoconus suspect, and healthy eyes. Eur J Ophthalmol. 2020;30(6):1506–1511. DOI: 10.1177/1120672120952034.
6. Craig J.P., Nichols K.K., Akpek E.K. et al. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017;15(3):276–283. DOI: 10.1016/j.jtos.2017.05.008.
7. Loh I.P., Sherwin T. Is keratoconus an inflammatory disease? The implication of inflammatory pathways. Ocul Immunol Inflamm. 2022;30(1):246–255. DOI: 10.1080/09273948.2020.1780271.
8. Lema I., Durán J.A. Inflammatory molecules in the tears of patients with keratoconus. Ophthalmology. 2005;112(4):654–659. DOI: 10.1016/j.ophtha.2004.11.050.
9. Lema I., Sobrino T., Durán J.A. et al. Subclinical keratoconus and inflammatory molecules from tears. Br J Ophthalmol. 2009;93(6):820–824. DOI: 10.1136/bjo.2008.144253.
10. D’Souza S., Nair A.P., Sahu G.R. et al. Keratoconus patients exhibit a distinct ocular surface immune cell and inflammatory profile. Sci Rep. 2021;11(1):20891. DOI: 10.1038/s41598-021-99805-9.
11. Solomon A., Dursun D., Liu Z. et al. Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease. Invest Ophthalmol Vis Sci. 2001;42(10):2283–2292.
12. Perez V.L., Stern M.E., Pflugfelder S.C. Inflammatory basis for dry eye disease flares. Exp Eye Res. 2020;201:108294. DOI: 10.1016/j.exer.2020.108294.
13. Brzhesky V.V., Egorova G.B., Egorov E.A. Dry eye syndrome and ocular surface diseases: clinic, diagnosis, treatment. Moscow: GEOTAR-Media; 2016 (in Russ.).
14. Dogru M., Karakaya H., Ozçetin H. et al. Tear function and ocular surface changes in keratoconus. Ophthalmology. 2003;110(6):1110–1118. DOI: 10.1016/S0161-6420(03)00261-6.
15. Harrison R.J., Klouda P.T., Easty D.L. et al. Association between keratoconus and atopy. Br J Ophthalmol. 1989;73(10):816–822. DOI: 10.1136/bjo.73.10.816.
16. Rahi A., Davies P., Ruben M. et al. Keratoconus and coexisting atopic disease. Br J Ophthalmol. 1977;61(12):761–764. DOI: 10.1136/bjo.61.12.761.
17. Khor W.B., Wei R.H., Lim L. et al. Keratoconus in Asians: demographics, clinical characteristics and visual function in a hospital-based population. Clin Exp Ophthalmol. 2011;39(4):299–307. DOI: 10.1111/j.1442-9071.2010.02458.x.
18. Owens H., Gamble G. A profile of keratoconus in New Zealand. Cornea. 2003;22(2):122–125. DOI: 10.1097/00003226-200303000-00008.
19. Mostovoy D., Vinker S., Mimouni M. et al. The association of keratoconus with blepharitis. Clin Exp Optom. 2018;101(3):339–344. DOI: 10.1111/cxo.12643.
20. Pinto R.D.P., Abe R.Y., Gomes F.C. et al. Meibomian gland dysfunction and dry eye in keratoconus. Arq Bras Oftalmol. 2021:S0004–27492021005008209. (Online ahead of print.) DOI: 10.5935/0004-2749.20220056.
21. Feizi S., Javadi M.A., Alemzadeh-Ansari M. et al. Management of corneal complications in vernal keratoconjunctivitis: A review. Ocul Surf. 2021;19:282–289. DOI: 10.1016/j.jtos.2020.10.005.
22. Dienes L., Kiss H.J., Perényi K. et al. corneal sensitivity and dry eye symptoms in patients with keratoconus. PLoS One. 2015;10(10):e0141621. DOI: 10.1371/journal.pone.0141621.
23. Bubnova I., Surnina Z., Averich V., Sarkisova K. Effect of corneal collagen crosslinking on the corneal structure in keratoconus. Vestnik Oftalmologii. 2020;136(5):268–276 (in Russ.). DOI: 10.17116/oftalma2020136052268.
24. Avetisov S.E., Bubnova I.A., Surnina Z.V. et al. Changes in cornea structure after corneal collagen crosslinking in keratoconus. Meditsinskiy Sovet. 2022;16(6):226–233 (in Russ.). DOI: 10.21518/2079-701X-2022-16-6-226-233.
25. Lema I., Durán J.A., Ruiz C. et al. Inflammatory response to contact lenses in patients with keratoconus compared with myopic subjects. Cornea. 2008;27(7):758–763. DOI: 10.1097/ICO.0b013e31816a3591.
26. López-de la Rosa A., González-García M.J., Calonge M., Enríquez-de-Salamanca A. Tear inflammatory molecules in contact lens wearers: a literature review. Curr Med Chem. 2020;27(4):523–548. DOI: 10.2174/0929867326666190409152921.
27. Mazzotta C., Raiskup F., Baiocchi S. et al. crosslinking results and literature overview. management of early progressive corneal ectasia: Springer; 2017: 33–62.
28. Bubnova I.A., Egorova G.B., Averich V.V., Mitichkina T.S. Medical treatment for dry eye in patients with keratoconus after corneal cross-linking. Russian Journal of Clinical Ophthalmology. 2020;20(2):67–71 (in Russ.). DOI: 10.32364/2311-7729-2020-20-2-67-71.
29. Voronin G.V., Bubnova I.A., Averich V.V., Sarkisova K.G. Precorneal tear film after corneal collagen cross-linking in keratoconus (preliminary report). Vestnik Oftalmologii. 2021;137(5):224–230 (in Russ.). DOI: 10.17116/oftalma2021137052224.
30. Vastardis I., Gatzioufas Z., McLintock C. et al. Tear film parameters before and after intracorneal ring segment implantation in keratoconic eyes. Eur J Ophthalmol. 2021;31(5):2213–2218. DOI: 10.1177/1120672120958301.
31. Egorova G.B., Mitichkina T.S., Shamsudinova A.R. Corneal protection in contact lens users. Vestnik Oftalmologii. 2014;130(2):57–64 (in Russ.).
32. Aragona P., Papa V., Micali A. et al. Long term treatment with sodium hyaluronate — containing artificial tears reduces ocular surface damage in patients with dry eye. Br J Ophthalmol. 2002;86(2):181–184. DOI: 10.1136/bjo.86.2.181.
33. Johnson M.E., Murphy P.J., Boulton M. Effectiveness of sodium hyaluronate eyedrops in the treatment of dry eye. Graefes Arch Clin Exp Ophthalmol. 2006;244(1):109–112.
34. Nishida T., Nakamura M., Mishima H., Otori T. Hyaluronan stimulates corneal epithelial migration. Exp Eye Res. 1991;53:753–758. DOI: 10.1016/0014-4835(91)90110-z.
35. Egorova G.B., Fedorov A.A., Mitichkina T.S. et al. Influence of tear substitutes and corneoprotective therapy on a condition of ocular surface in patients with dry eye syndrome. Russian Journal of Clinical Ophthalmology. 2015;16(1):17–23 (in Russ.).
36. Jain S., Singh S., Nagar A. Brief communication: Dexpanthenol and its ophthalmic uses. J Clin Exp Ophthalmol. 2017;8(5):678. DOI: 10.4172/2155-9570.1000678.
37. Kobayashi D., Kusama M., Onda M., Nakahata N. The effect of pantothenic acid deficiency on keratinocyte proliferation and the synthesis of keratinocyte growth factor and collagen in fibroblasts. J Pharmacol Sci. 2011;115(2):230–234. DOI: 10.1254/jphs.10224sc.
38. Rybakova E.G., Egorova G.B., Kalinich N.I. Corneregel — new stimulator of reparative regeneration. Russian Journal of Clinical Ophthalmology. 2001;4:162 (in Russ.).
39. Wilson C.G., Zhu Y.P., Frier M. et al. Ocular contact time of a carbomer gel (GelTears) in humans. Br J Ophthalmol. 1998;82(10):1131–1134. DOI: 10.1136/bjo.82.10.1131.
40. Kukhtenko G.P., Popova T.V., Gladukh Ie.V., Kukhtenko A.S. Comparative analysis of carbomer polymers for pharmaceutical and cosmetic practice Zaporozhye medical journal. 2020;22(3):431–436 (in Russ.).
41. Anurova M.N., Bakhrushina E.O., Lapik I.V., Krechetov S.P. The determination of the rheological optimum of ophthalmic gels. Modern aspects of the ophthalmic dosage forms development. Drug development & registration. 2017;(4):64–70 (in Russ.).
42. Rajoria G. Gupta A. In-Situ Gelling System: A Novel Approach for Ocular Drug Delivery. Am J Pharm Tech Res. 2012;2(4):24–53.
43. Gross D., Tekster A. Report on biological assessment and clinical evaluation of the drug PARIN-POS. Edition 005. Translation from English and German. 2015 (in Russ.).
44. Egorova G.B., Mitichkina T.S., Shamsudinova A.R. Evaluation of Restasis usage in contact lens wearers with dry eye syndrome. Russian Journal of Clinical Ophthalmology. 2014;14(4):198–202 (in Russ.).
45. Shorter E., Harthan J., Nau A. et al. Dry eye symptoms in individuals with keratoconus wearing contact lenses. Eye Contact Lens. 2021;47(9):515–519. DOI: 10.1097/ICL.0000000000000802.
46. Fedotova K., Grabovetsky V.R., Novikov S.A., Ezugbaya M. Miniscleral lenses in the treatment of patients with dry eye syndrome (first own experience). Ophthalmology Journal. 2019;12(1):5–12 (in Russ.). DOI: 10.17816/OV1215-12.
47. Listratov S.V., Bakalova N.A., Averich V.V. OKVision® SMARTFIT™ scleral contact lens manufacturing technology. The EYE GLAZ. 2021;23(2):47–52 (in Russ.). DOI: 10.33791/2222-4408-2021-2-47-52.
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