Approach

Treatment aims to restore and maintain homeostatic ocular surface function and to improve quality of life.[1] 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] 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]

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] There are many lubricant preparations available commercially that vary in electrolyte concentration, preservative concentration, osmolarity, and viscosity. However, most formulations have similar efficacies.[38] 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][39][40][41][42][43][44][45][46][47][48]

  • 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] However, poor compliance commonly undermines the effectiveness of these compresses. Various warm compression devices have been created to treat meibomian gland dysfunction.[3]

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]

  • 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] Further large, high-quality, randomized controlled trials (RCTs) are warranted to confirm the effect.[49][50] 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]

  • 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]

  • Permanent punctal occlusion: an option if patients notice significant improvement with therapeutic trials of absorbable/nonabsorbable punctal plugs.[51] The primary concern with permanent occlusion is irreversible epiphora.

There are various adjuncts to ongoing treatments.[2]

  • 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]

  • Thermal pulsation (e.g., LipiFlow®) and intense pulsed light treatments: limited evidence supports both of these approaches to meibomian gland dysfunction.[3][53][54] One Cochrane review concluded that LipiFlow® performs similarly to commonly used treatments for DED.[54] An earlier Cochrane review concluded that there is a scarcity of RCT evidence for intense pulsed light therapy.[53]

  • Adjunctive secretagogues (cholinergic agonists): used for patients with Sjögren syndrome-associated keratoconjunctivitis sicca.[55]

  • Cyclosporine eye drops: approved for use in patients with chronic dry eyes and repressed tear production.[3] One Cochrane review concluded that the evidence for cyclosporine eye drops in the management of DED is inconsistent.[56] Published trials were short-term; larger and longer-term clinical trials are required to establish therapeutic efficacy and safety.[56] 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][57] Dry eye surgery is highly specialized and patient selection is made on an individual basis.

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