Treatment aims to restore and maintain homeostatic ocular surface function and to improve quality of life.[1]Hakim FE, Farooq AV. Dry eye disease: an update in 2022. JAMA. 2022 Feb 1;327(5):478-9.
http://www.ncbi.nlm.nih.gov/pubmed/35103781?tool=bestpractice.com
Visual acuity and clinical findings usually support treatment efficacy and inform when next line or adjunct treatments should be started. Symptom resolution is difficult to achieve and interventions usually only reduce symptoms.[2]Amescua G, Ahmad S, Cheung AY, et al. Dry eye syndrome preferred practice pattern®. Ophthalmology. 2024 Apr;131(4):P1-49.
https://www.doi.org/10.1016/j.ophtha.2023.12.041
http://www.ncbi.nlm.nih.gov/pubmed/38349301?tool=bestpractice.com
Management is therefore aggressive, aiming to reduce or alleviate signs and symptoms (e.g., ocular irritation, redness, or mucus discharge), maintain or improve visual function, and reduce or prevent ocular surface damage (e.g., long-term sequelae such as vascularization).[2]Amescua G, Ahmad S, Cheung AY, et al. Dry eye syndrome preferred practice pattern®. Ophthalmology. 2024 Apr;131(4):P1-49.
https://www.doi.org/10.1016/j.ophtha.2023.12.041
http://www.ncbi.nlm.nih.gov/pubmed/38349301?tool=bestpractice.com
Long-term treatment is usually required and combines:
First-line treatment with topical lubricants
Second-line treatment with oral tetracyclines (in patients with meibomian gland dysfunction/blepharitis), topical ophthalmic corticosteroids, punctal plugs, and moisture chamber spectacles
Ongoing therapy with cyclosporine, autologous serum eye drops, scleral contact lenses, and permanent punctal occlusion.
At initial presentation
Topical lubricants are used as first-line treatments to help ocular surfaces regain their normal homeostatic states however, their clinical effect is poorly understood.[3]Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017 Jul;15(3):276-83.
https://www.sciencedirect.com/science/article/pii/S1542012417301192?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/28736335?tool=bestpractice.com
There are many lubricant preparations available commercially that vary in electrolyte concentration, preservative concentration, osmolarity, and viscosity. However, most formulations have similar efficacies.[38]Pucker AD, Ng SM, Nichols JJ. Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database Syst Rev. 2016 Feb 23;(2):CD009729.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009729.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/26905373?tool=bestpractice.com
Patients will usually try several preparations before finding one that suits them. Lubricant use is continued throughout treatment.
Patients often require several viscosity-enhancing agents to enhance lubrication and prolong retention times on the ocular surface. Treatment options may include carbomer (polyacrylic acid), carmellose (carboxymethylcellulose), dextran, hyaluronic acid/sodium hyaluronate, hydroxypropyl guar, hypromellose (hydroxypropyl methylcellulose), polyvinyl alcohol, polyvinylpyrrolidone, and polyethylene glycol. Availability varies between countries.
Mild symptoms: can usually be managed satisfactorily with lubricants and lipid tear eye drops, along with lifestyle changes. Treatment can be started with hypromellose (0.3% or 0.5%), moving onto carmellose (0.5%), and then carbomer (0.2%). In predominantly evaporative dry eyes a lipid tear supplement eye drop is added.
Moderate symptoms: may include blurred vision and light sensitivity and may restrict daily activities. They require more frequent use of tear supplements and/or use of a more viscous product. Treatment includes sodium hyaluronate (0.1%) and carmellose (1%).
Severe symptoms: present as more pronounced due to desiccation of the corneal epithelium. Regular use of tear supplements and more viscous and gel lubricants should be beneficial. Additional treatments may be required. Most patients in this group need combination treatment with sodium hyaluronate (0.2%), hydroxypropyl guar, and paraffin-based ointments.
Night time treatment with white soft paraffin and retinol palmitate, light liquid paraffin and wool fat, or other combinations containing white soft paraffin and mineral oil, can be used to support these treatments.
Second-line treatment options
Options considered if patients remain symptomatic despite topical lubricants:[2]Amescua G, Ahmad S, Cheung AY, et al. Dry eye syndrome preferred practice pattern®. Ophthalmology. 2024 Apr;131(4):P1-49.
https://www.doi.org/10.1016/j.ophtha.2023.12.041
http://www.ncbi.nlm.nih.gov/pubmed/38349301?tool=bestpractice.com
[39]Shine WE, McCulley JP, Pandya AG. Minocycline effect on meibomian gland lipids in meibomianitis patients. Exp Eye Res. 2003 Apr;76(4):417-20.
http://www.ncbi.nlm.nih.gov/pubmed/12634106?tool=bestpractice.com
[40]Solomon A, Rosenblatt M, Li D, et al. Doxcycline inhibition of interleukin-1 in the corneal epithelium. Invest Ophthalmol Vis Sci. 2000 Aug;41(9):2544-57.
http://iovs.arvojournals.org/article.aspx?articleid=2162778
http://www.ncbi.nlm.nih.gov/pubmed/10937565?tool=bestpractice.com
[41]Tamago RJ, Bok RA, Brem H. Angiogenesis inhibition by minocycline. Cancer Res. 1991 Jan 15;51(2):672-5.
http://cancerres.aacrjournals.org/content/canres/51/2/672.full.pdf
http://www.ncbi.nlm.nih.gov/pubmed/1702361?tool=bestpractice.com
[42]Pflugfelder SC. Antiinflammatory therapy for dry eye. Am J Ophthalmol. 2004 Feb;137(2):337-42.
http://www.ncbi.nlm.nih.gov/pubmed/14962426?tool=bestpractice.com
[43]Liu SH, Saldanha IJ, Abraham AG, et al. Topical corticosteroids for dry eye. Cochrane Database Syst Rev. 2022 Oct 21;10(10):CD015070.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015070.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/36269562?tool=bestpractice.com
[44]Tost FH, Geerling G. Plugs for occlusion of the lacrimal drainage system.
Dev Ophthalmol. 2008;41:193-212.
http://www.ncbi.nlm.nih.gov/pubmed/18453770?tool=bestpractice.com
[45]Tuberville AW, Frederick WR, Wood TO. Punctal occlusion in tear deficiency syndromes. Ophthalmology. 1982 Oct;89(10):1170-2.
http://www.ncbi.nlm.nih.gov/pubmed/7155528?tool=bestpractice.com
[46]Ervin AM, Law A, Pucker AD. Punctal occlusion for dry eye syndrome. Cochrane Database Syst Rev. 2017 Jun 26;(6):CD006775.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006775.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/28649802?tool=bestpractice.com
[47]Tsubota K. The effect of wearing spectacles on the humidity of the eye. Am J Ophthalmol. 1989 Jul 15;108(1):92-3.
http://www.ncbi.nlm.nih.gov/pubmed/2750844?tool=bestpractice.com
[48]Shen G, Qi Q, Ma X. Effect of moisture chamber spectacles on tear functions in dry eye disease. Optom Vis Sci. 2016 Feb;93(2):158-64.
http://www.ncbi.nlm.nih.gov/pubmed/26704145?tool=bestpractice.com
Tetracycline antibiotics: have antimicrobial, anti-inflammatory, and antiangiogenic properties. Generally used for around 3 months, but this varies with patient response to treatment.
Topical ophthalmic corticosteroids: evidence suggests that short-term use may be beneficial; potential adverse effects should be discussed before treatment and monitored throughout (e.g., glaucoma and cataract).
Punctal plugs: absorbable and nonabsorbable punctal plugs have been shown to increase tear retention. Contraindications include sensitivity to plug insertion and chronic lacrimal sac inflammation.
Moisture chamber spectacles: efficacy has been reported, but their use is not particularly widespread.
Patients with underlying meibomian gland dysfunction are encouraged to perform regular lid hygiene and apply warm compresses in conjunction with the regular use of lubricants.[2]Amescua G, Ahmad S, Cheung AY, et al. Dry eye syndrome preferred practice pattern®. Ophthalmology. 2024 Apr;131(4):P1-49.
https://www.doi.org/10.1016/j.ophtha.2023.12.041
http://www.ncbi.nlm.nih.gov/pubmed/38349301?tool=bestpractice.com
However, poor compliance commonly undermines the effectiveness of these compresses. Various warm compression devices have been created to treat meibomian gland dysfunction.[3]Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017 Jul;15(3):276-83.
https://www.sciencedirect.com/science/article/pii/S1542012417301192?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/28736335?tool=bestpractice.com
Long-term treatment
Ongoing therapies are generally used in conjunction with initial treatments (e.g., topical lubricants, lid hygiene/warm compresses for meibomian gland dysfunction/blepharitis).[2]Amescua G, Ahmad S, Cheung AY, et al. Dry eye syndrome preferred practice pattern®. Ophthalmology. 2024 Apr;131(4):P1-49.
https://www.doi.org/10.1016/j.ophtha.2023.12.041
http://www.ncbi.nlm.nih.gov/pubmed/38349301?tool=bestpractice.com
Autologous serum eye drops: the fluid component of postclotted blood can be produced from unpreserved blood preparations. One meta-analysis reported that there may be some improvement in symptoms compared with artificial tears in the short term only (first 2 weeks of treatment).[49]Pan Q, Angelina A, Marrone M, et al. Autologous serum eye drops for dry eye. Cochrane Database Syst Rev. 2017 Feb 28;(2):CD009327.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009327.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/28245347?tool=bestpractice.com
Further large, high-quality, randomized controlled trials (RCTs) are warranted to confirm the effect.[49]Pan Q, Angelina A, Marrone M, et al. Autologous serum eye drops for dry eye. Cochrane Database Syst Rev. 2017 Feb 28;(2):CD009327.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009327.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/28245347?tool=bestpractice.com
[50]Shtein RM, Shen JF, Kuo AN, et al. Autologous serum-based eye drops for treatment of ocular surface disease: a report by the American Academy of Ophthalmology. Ophthalmology. 2020 Jan;127(1):128-33.
https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0161642019319463
http://www.ncbi.nlm.nih.gov/pubmed/31561880?tool=bestpractice.com
Temporary vision blurring may occur. Autologous serum eye drops are time-consuming to prepare. Other biologic tear substitutes such as allogeneic serum, umbilical cord serum, and autologous platelet lysate drops may also be used to improve dry eye disease (DED).[49]Pan Q, Angelina A, Marrone M, et al. Autologous serum eye drops for dry eye. Cochrane Database Syst Rev. 2017 Feb 28;(2):CD009327.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009327.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/28245347?tool=bestpractice.com
Scleral contact lenses: used to protect and hydrate corneal surfaces. Evidence suggests they may help with the healing of persistent corneal epithelial defects secondary to dry eye.[3]Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017 Jul;15(3):276-83.
https://www.sciencedirect.com/science/article/pii/S1542012417301192?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/28736335?tool=bestpractice.com
Permanent punctal occlusion: an option if patients notice significant improvement with therapeutic trials of absorbable/nonabsorbable punctal plugs.[51]Geerling G, Tost FH. Surgical occlusion of the lacrimal drainage system. Dev Ophthalmol. 2008;41:213-29.
http://www.ncbi.nlm.nih.gov/pubmed/18453771?tool=bestpractice.com
The primary concern with permanent occlusion is irreversible epiphora.
There are various adjuncts to ongoing treatments.[2]Amescua G, Ahmad S, Cheung AY, et al. Dry eye syndrome preferred practice pattern®. Ophthalmology. 2024 Apr;131(4):P1-49.
https://www.doi.org/10.1016/j.ophtha.2023.12.041
http://www.ncbi.nlm.nih.gov/pubmed/38349301?tool=bestpractice.com
Antibiotics: evidence suggests that long-term adjunctive treatment with topical antibiotics (e.g., erythromycin ophthalmic gel, azithromycin ophthalmic drops) or low-dose oral doxycycline is effective for patients with chronic meibomian gland dysfunction/blepharitis.[52]Yoo SE, Lee DC, Chang MH. The effect of low-dose doxycycline therapy in chronic meibomian gland dysfunction. Korean J Ophthalmol. 2005 Dec;19(4):258-63.
http://www.ncbi.nlm.nih.gov/pubmed/16491814?tool=bestpractice.com
Thermal pulsation (e.g., LipiFlow®) and intense pulsed light treatments: limited evidence supports both of these approaches to meibomian gland dysfunction.[3]Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017 Jul;15(3):276-83.
https://www.sciencedirect.com/science/article/pii/S1542012417301192?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/28736335?tool=bestpractice.com
[53]Cote S, Zhang AC, Ahmadzai V, et al. Intense pulsed light (IPL) therapy for the treatment of meibomian gland dysfunction. Cochrane Database Syst Rev. 2020 Mar 18;3(3):CD013559.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013559/full
http://www.ncbi.nlm.nih.gov/pubmed/32182637?tool=bestpractice.com
[54]Pucker AD, Yim TW, Rueff E, et al. LipiFlow for the treatment of dry eye disease. Cochrane Database Syst Rev. 2024 Feb 5;2(2):CD015448.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015448.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/38314898?tool=bestpractice.com
One Cochrane review concluded that LipiFlow® performs similarly to commonly used treatments for DED.[54]Pucker AD, Yim TW, Rueff E, et al. LipiFlow for the treatment of dry eye disease. Cochrane Database Syst Rev. 2024 Feb 5;2(2):CD015448.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015448.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/38314898?tool=bestpractice.com
An earlier Cochrane review concluded that there is a scarcity of RCT evidence for intense pulsed light therapy.[53]Cote S, Zhang AC, Ahmadzai V, et al. Intense pulsed light (IPL) therapy for the treatment of meibomian gland dysfunction. Cochrane Database Syst Rev. 2020 Mar 18;3(3):CD013559.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013559/full
http://www.ncbi.nlm.nih.gov/pubmed/32182637?tool=bestpractice.com
Adjunctive secretagogues (cholinergic agonists): used for patients with Sjögren syndrome-associated keratoconjunctivitis sicca.[55]Tsifetaki N, Kitsos G, Paschides CA, et al. Oral pilocarpine for the treatment of ocular symptoms in patients with Sjogren's syndrome: a randomized 12 week study. Ann Rheum Dis. 2003 Dec;62(12):1204-7.
http://ard.bmj.com/content/62/12/1204.long
http://www.ncbi.nlm.nih.gov/pubmed/14644860?tool=bestpractice.com
Cyclosporine eye drops: approved for use in patients with chronic dry eyes and repressed tear production.[3]Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017 Jul;15(3):276-83.
https://www.sciencedirect.com/science/article/pii/S1542012417301192?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/28736335?tool=bestpractice.com
One Cochrane review concluded that the evidence for cyclosporine eye drops in the management of DED is inconsistent.[56]de Paiva CS, Pflugfelder SC, Ng SM, et al. Topical cyclosporine A therapy for dry eye syndrome. Cochrane Database Syst Rev. 2019 Sep 13;9(9):CD010051.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010051.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/31517988?tool=bestpractice.com
Published trials were short-term; larger and longer-term clinical trials are required to establish therapeutic efficacy and safety.[56]de Paiva CS, Pflugfelder SC, Ng SM, et al. Topical cyclosporine A therapy for dry eye syndrome. Cochrane Database Syst Rev. 2019 Sep 13;9(9):CD010051.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010051.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/31517988?tool=bestpractice.com
Cyclosporine eye drops are typically given as a second-line or adjunctive treatment and can be used in combination with any other treatment. However, practice varies and topical cyclosporine may be used earlier.
Maintenance therapies should be continued until symptoms improve or disappear; however, this will depend on the patient and treatment is often lifelong.
Surgery
Surgery is rarely performed. However, small numbers of patients with end-stage dry eye may be suitable for certain surgical approaches. End-stage dry eye may be defined as dry eye with continued ocular surface damage despite maximal medical treatment.
Surgical treatments include amniotic membrane transplantation, lid tarsorrhaphy, and, more rarely, transplantation of salivary gland tissue onto the ocular surface.[2]Amescua G, Ahmad S, Cheung AY, et al. Dry eye syndrome preferred practice pattern®. Ophthalmology. 2024 Apr;131(4):P1-49.
https://www.doi.org/10.1016/j.ophtha.2023.12.041
http://www.ncbi.nlm.nih.gov/pubmed/38349301?tool=bestpractice.com
[57]Geerling G, Sieg P. Transplantation of the major salivary glands. Dev Ophthalmol. 2008;41:255-68.
http://www.ncbi.nlm.nih.gov/pubmed/18453774?tool=bestpractice.com
Dry eye surgery is highly specialized and patient selection is made on an individual basis.