Advertisement

PentaVision

Ophthalmology Management

Article

Medical Management of Dry Eye Disease

A look at the latest solutions to treat this growing health burden

By: ETHAN S. LINDGREN, BS, NEEL D. PASRICHA, MD
Ophthalmology Management April 1, 2023 Vol 27, Issue April 2023 Page(s): 20, 22, 24, 25

Dry eye disease (DED) is a multifactorial disease characterized by a loss of homeostasis in the tear film leading to tear film instability and hyperosmolarity, as well as ocular surface inflammation and damage.1 In the United States, an estimated 6.8% of adults (~16.4 million people) have a DED diagnosis, with a global prevalence as high as 54%, creating a $55 billion burden for the US economy annually.2,3 The purpose of this article is to provide an update on the medical solutions available to treat DED.

ENVIRONMENTAL, OCCUPATIONAL AND BEHAVIORAL MODIFICATIONS

DED is associated with sedentary, indoor occupations with high screen use as well as environmental factors such as low humidity, high temperature, high altitude and air pollutants.4,5 Individuals can mitigate some of these risk factors by using indoor humidifiers and avoiding aerosol consumer products such as hairspray or air freshener.5

For occupations that require high screen time, the “20-20-20 rule” is recommended — individuals look at an object that is 20 feet away every 20 minutes for 20 seconds.6 Behavioral modifications like blinking exercises, where patients close their eyes normally for 2 seconds, open their eyes normally for 2 seconds and then squeeze their eyelids shut for 2 seconds, were found to decrease self-reported symptoms of DED and increase tear break-up time.7

These strategies are more likely to be implemented if the patient understands the relationship between the screen use and/or environmental factors and DED.7 It is therefore essential for the clinician to inform them of these relationships.

LUBRICANTS

Ocular surface toxicity from the most common preservative in drops, benzalkonium chloride (BAK), has contributed to the adoption of preservative-free drops, which have been shown to decrease the severity of DED.8,9 One disadvantage of preservative-free drops is that they have traditionally required single-dose packaging to maintain sterility, making them more expensive.10

However, recent innovations have been employed to maintain sterility of preservative-free drops in multi-dose bottles.8 Hyaluronic acid, polyethylene glycol and carboxymethylcellulose sodium are present in many drops for their ability to promote healing of the ocular surface epithelium.11-14 Mineral oil and glycerin are notable for their ability to prolong tear retention time and improve tear volume, respectively (Table 1).15,16

TABLE 1. PRESERVATIVE-FREE ARTIFICIAL TEAR LUBRICANTS
TYPE NAME (SUPPLIER) COMPOSITION NOTES
Aqueous Dry Eye Therapy (TheraTears)
  • Carboxymethylcellulose sodium 0.25%
 Ionically balanced tears.
Dry Eye Therapy Extra (TheraTears)
  • Carboxymethylcellulose sodium 0.25%
  • Trehalose (inactive)
 Trehalose is a bioprotective agent.17,18
Refresh Classic (Allergan)
  • Polyvinyl alcohol 1.4%
  • Povidone 0.6%
 Polyvinyl alcohol prolongs drug’s retention time on the ocular surface without inducing ocular surface inflammation.19
Refresh Plus (Allergan)
  • Carboxymethylcellulose sodium 0.5%
  
Retaine CMC Lubricant Eye Drops (OCuSOFT)
  • Carboxymethylcellulose sodium 0.5%
  
Retaine HPMC Lubricant Eye Drops (OCuSOFT)
  • Hypromellose 0.3%
 Multidose (COMOD bottle). Hypromellose is shown to decrease the signs and symptoms of individuals with DED.20
Sterile Lubricant Eye Drops (Ivizia)
  • Povidone 0.5%
  • Trehalose (inactive)
  • Sodium hyaluronate (inactive)
 Povidone increases tear stability21
Oil Oasis Tears PF (Oasis Medical)
  • Glycerin 0.22%
 Multidose or single use
Oasis Tears PF Plus (Oasis Medical)
  • Glycerin 0.25%
 Multidose
Biotrue Eye Drops (Bausch + Lomb)
  • Glycerin 0.5%
 Multidose
Retaine MGD Emulsion Eye Drops (OCuSOFT)
  • Light mineral oil 0.5%
  • Mineral oil 0.5%
 Lipid replenishing formula uses electrostatic attraction to stabilize tear film.
Soothe XP Emollient Eye Drops (Bausch + Lomb)
  • Light mineral oil 1%
  • Mineral oil 4.5%
  
Blink Tears (Johnson & Johnson Vision)
  • Polyethylene glycol 400 0.25%
  
Systane Ultra PF (Alcon)
  • Polyethylene glycol 400 0.4%
  • Propylene glycol 0.3%
 Propylene glycol augments tear film stability.11
Systane Hydration PF (Alcon)
  • Polyethylene glycol 400 0.4%
  • Propylene glycol 0.3%
  • Sodium hyaluronate (inactive)
  
Refresh Optive (Allergan)
  • Carboxymethylcellulose sodium 0.5%
  • Glycerin 0.9%
  
Refresh Optive Advanced (Allergan)
  • Carboxymethylcellulose sodium 0.5%
  • Glycerin 1%
  • Polysorbate 80 0.5%
 Polysorbate 80 is used to mimic the lipid aspect of the tear film.22
Refresh Optive Mega-3 (Allergan)
  • Carboxymethylcellulose sodium 0.5%
  • Glycerin 1%
  • Polysorbate 80 0.5%
  • Flaxseed oil (inactive)
 Flaxseed oil, a short chain omega-3 fatty acid, reduces ocular surface inflammation.23
Gel Liquid Gel Nighttime Dry Eye Therapy (TheraTears)
  • Carboxymethylcellulose sodium 1%
  
Refresh Celluvisc (Allergan)
  • Carboxymethylcellulose sodium 1%
  
Refresh Optive Gel Drops (Allergan)
  • Carboxymethylcellulose sodium 1%
  • Glycerin 0.9%
  
Ointment Systane Nighttime (Alcon)
  • Mineral oil 3%
  • White petrolatum 94%
  • Lanolin 3%
  
Retaine PM (OCuSOFT)
  • Mineral oil 20%
  • White petrolatum 80%
  
Soothe Nighttime (Bausch + Lomb)
  • Mineral oil 20%
  • White petrolatum 80%
  
Refresh Lacri-Lube (Allergan)
  • Mineral oil 42.5%
  • White petrolatum 56.8%
  • Lanolin alcohols
 Lanolin alcohol is a potential allergen.24,25
Refresh PM (Allergan)
  • Mineral oil 42.5%
  • White petrolatum 57.3%
  • Lanolin alcohols
  

ANTERIOR BLEPHARITIS

Eyelid cleansers treat anterior blepharitis and improve overall ocular comfort (Table 2).26,27 Anterior blepharitis is characterized by inflammation where the eyelash attaches to the eyelid, leading to ocular discomfort and DED.28 This condition is recognizable by the presence of scurf (seborrheic blepharitis aka dandruff) or sleeves (Demodex mites) around the eyelash.29,30 Tea tree oil (TTO) is a natural oil that has demonstrated efficacy killing Demodex mites.31 Additionally, ivermectin 1% (Soolantra, Galderma) cream, an anti-parasitic and anti-inflammatory therapy, can eradicate Demodex mites and reduce inflammation when applied to the eyelash once weekly for 15 minutes.32 TP-03 (lotilaner ophthalmic solution 0.25%) is a promising therapeutic from Tarsus Pharmaceuticals in the clinical trial pipeline that has the potential to eradicate Demodex by inhibiting parasite specific GABA-Cl-channels.33

TABLE 2. EYELID CLEANSERS
COMPOSITION NAME (SUPPLIER) COMMENT
Non-TTO liquid HypoChlor Liquid Spray (OCuSOFT) Electrochemically activated solution.
SteriLid Antimicrobial Eyelid Cleanser and Facial Wash (TheraTears) Improves eyelid inflammation and tear break-up time.34
Non-TTO foam Baby Shampoo (Johnson & Johnson)  
Lid Scrub Original Foaming Eyelid Cleanser (OCuSOFT)  
Lid Scrub Plus Foaming Eyelid Cleanser (OCuSOFT) Uses modified Ringer’s solution rather than water.
Lid Scrub Plus Platinum Foam (OCuSOFT) Contains an additional anti-inflammatory agent (PSG-2)
Non-TTO pad Lid Scrub Plus Pre-Moistened Pads (OCuSOFT)  
Systane Lid Wipes (Alcon)  
TTO liquid Oust Demodex Cleanser (OCuSOFT)  
TTO foam Cliradex Light Foam (Cliradex) Has higher concentrations of 4-Terpineol (T4O), which is the main component of TTO.
Tea Tree Cleanser – Gentle (Eye Eco) 1% TTO.
Tea Tree Cleanser – Advanced (Eye Eco) 2% TTO.
TTO pad Lid Scrub Allergy Eyelid Cleanser Pad (OCuSOFT) Contains an additional anti-inflammatory agent (PSG-2)
Cliradex Towelettes (Cliradex) Has higher concentrations of T4O.

OCULAR ROSACEA/MGD/POSTERIOR BLEPHARITIS

Ocular rosacea, often referred to as meibomian gland dysfunction (MGD) or posterior blepharitis, is a chronic inflammatory condition that involves the clogging of meibomian glands that can lead to evaporative DED.35 The lifestyle changes and eyelid hygiene discussed above can have positive impacts on ocular rosacea.35,36 Management includes warm compresses and anti-inflammatory topical and systemic therapies.35 Warm compresses are used to enhance the delivery of oil from the meibomian glands into the tear film, providing increased tear stability.37 Commercially available microwaveable warm compresses (eg, Bruder’s Moist Heat Eye Compress and USB-chargeable warm compresses (eg, Wizard Research’s electric heated Dry Eye Mask) are among the most popular.

Antibiotics are administered at lower doses to harness their anti-inflammatory properties in addition to their antimicrobial ones (Table 3).38 Low concentration topical tacrolimus ointment (0.03% or 0.1%) applied twice daily to the eyelids and eyes can be utilized to suppress the inflammatory responses on the ocular surface.39 Despite the DREAM study showing no significant improvement in DED with omega-3 supplementation, other studies suggest supplementation with omega-3 fatty acids ameliorate the signs and symptoms of DED.40,41

TABLE 3. ANTIBIOTIC ROSACEA MANAGEMENT
NAME COMMENT
Oral Doxycycline USP (Oracea, Galderma Laboratories) 40 mg (30 mg immediate release, 10 mg delayed release). Once daily Oracea reduced relapse rate and inflammatory lesions in individuals with rosacea.42,43
Oral Doxycycline monohydrate (generic) 50 mg daily dosing of doxycycline monohydrate for 3-6 months is more cost effective than doxycycline hyclate and leads to fewer GI symptoms due to reduced acidity.44
Oral Azithromycin 1 g weekly for 3 weeks in adults or 10 mg/kg weekly for 3-6 months in children led to improved symptoms and signs in patients with MGD and blepharokeratoconjunctivitis.45,46
Topical AzaSite (Azithromycin 1%) drop (Théa Pharma) Has BAK preservative. When administered twice daily for 2 days, and then once daily for 30 days, AzaSite significantly improved signs and symptoms of blepharitis.47
Topical Klarity-A (Azithromycin 1%) drop Preservative-free (ImprimisRx).
Topical Metronidazole 0.75% gel Twice daily application to the eyelids for 12 weeks significantly reduced ocular rosacea.48

ANTI-INFLAMMATORIES

Inflammation of the ocular surface is a significant component in both aqueous deficiency and evaporative DED.49 While there are many anti-inflammatory drugs in the clinical trials pipeline for DED, only four have been approved by the FDA to date. Both cyclosporine (Restasis, Allergan; Cequa, Sun Ophthalmics) and lifitegrast (Xiidra, Novartis) take several months to achieve maximum benefit, whereas loteprednol (Eysuvis, Kala Pharmaceuticals) is fast-acting but can only be used for up to 2 weeks (Table 4).50

TABLE 4. FDA-APPROVED ANTI-INFLAMMATORY THERAPIES
NAME (SUPPLIER) COMPOSITION
Restasis (Allergan) Cyclosporine 0.05%
Cequa (Sun Ophthalmics) Cyclosporine 0.09%
Xiidra (Novartis) Lifitegrast 5%
Eysuvis (Kala Pharmaceuticals) Loteprednol 0.2%

TEAR PRODUCTION STIMULANTS

Varenicline tartrate solution 0.03 mg (Tyrvaya, Oyster Point Pharma) is a preservative-free nasal spray of the nicotinic acetylcholine receptor agonist varenicline 0.03 mg, the same compound used in the smoking cessation drug CHANTIX.51 Tyrvaya stimulates tear production and offers the convenience of an intranasal route.51 Study subjects administered one spray (0.05 ml) of Tyrvaya in both nostrils twice daily for 4 weeks had significantly improved basal tear production by Schirmer’s test compared to the vehicle group.52,53 Ocular surface ion transporters are promising therapeutic targets for pro-secretory or anti-absorptive DED therapies.54 Transporters such as cystic fibrosis transmembrane conductance regulator, calcium-activated chloride channels and epithelial sodium channel are a few examples, with activators and inhibitors in the clinical trial pipeline.54

TEAR SUBSTITUTES

Blood- and platelet-derived therapies are becoming increasingly common for the treatment of DED.55,56 One example, serum tears, are used to treat severe DED due to their tear-like osmolality and pH levels with both antibacterial and anti-inflammatory properties.57,58 Serum is collected from the patient (autologous) or donor (allogeneic). One commercially available option for autologous serum tears is Vital Tears.59 Plasma rich growth factor is an alternative treatment that promotes tissue repair and eliminates the concern for disease transmission or immune response.57

Amniotic membrane extract eyedrops (AMEED), such as the commercially available Regener-Eyes, have high levels of growth factors and may be safe and efficacious in reducing the signs and symptoms of severe ocular surface disease.60,61 A review of AMEED showed that they have the potential to reduce inflammation, yet clinical data for the use of these drops remains limited.60

SCLERAL LENSES

Patients with severe DED have benefitted from scleral lenses, a rigid contact lens that covers and hydrates the cornea.62 These lenses are 12-25 mm in diameter with a fluid reservoir between the lens and the cornea.63,64

Two scleral lenses are PROSE (Boston Foundation for Sight) and EyePrintPro (EyePrint Prosthetics). PROSE uses a precise computer-assisted design system, but PROSE lenses cost up to $7,000 per eye and are only accessible at 15 sites across the United States.65-67 EyePrintPro uses a non-toxic mold to take an impression of the eye. Then, it is analyzed using EyePrint Designer software to develop a custom scleral lens that costs up to $4,000 per eye.67-70 OM

REFERENCES

  1. Craig JP, Nelson JD, Azar DT, et al. TFOS DEWS II Report Executive Summary. Ocul Surf. 2017;15(4):802-812.
  2. Farrand KF, Fridman M, Stillman IÖ, Schaumberg DA. Prevalence of Diagnosed Dry Eye Disease in the United States Among Adults Aged 18 Years and Older. Am J Ophthalmol. 2017;182:90-98.
  3. Yu J, Asche CV, Fairchild CJ. The economic burden of dry eye disease in the United States: a decision tree analysis. Cornea. 2011;30(4):379-387.
  4. Bazeer S, Jansonius N, Snieder H, Hammond C, Vehof J. The relationship between occupation and dry eye. Ocul Surf. 2019;17(3):484-490.
  5. Mandell JT, Idarraga M, Kumar N, Galor A. Impact of Air Pollution and Weather on Dry Eye. J Clin Med. 2020;9(11):3740. Published Nov 20, 2020.
  6. Tribley J, McClain S, Karbasi A, Kaldenberg J. Tips for computer vision syndrome relief and prevention. Work. 2011;39(1):85-87.
  7. Kim AD, Muntz A, Lee J, Wang MTM, Craig JP. Therapeutic benefits of blinking exercises in dry eye disease. Cont Lens Anterior Eye. 2021;44(3):101329.
  8. Walsh K, Jones L. The use of preservatives in dry eye drops. Clin Ophthalmol. 2019;13:1409-1425. Published Aug 1, 2019.
  9. Nasser L, Rozycka M, Gomez Rendon G, Navas A. Real-life results of switching from preserved to preservative-free artificial tears containing hyaluronate in patients with dry eye disease. Clin Ophthalmol. 2018;12:1519-1525. Published Aug 23, 2018
  10. Furrer P, Mayer JM, Gurny R. Ocular tolerance of preservatives and alternatives. Eur J Pharm Biopharm. 2002;53(3):263-280.
  11. Aguilar A, Berra M, Trédicce J, Berra A. Efficacy of polyethylene glycol-propylene glycol-based lubricant eye drops in reducing squamous metaplasia in patients with dry eye disease. Clin Ophthalmol. 2018;12:1237-1243. Published Jul 12, 2018
  12. Duan ZH, Tang YF. The clinical effects of sodium hyaluronate, polyethylene glycol, and dextran-70 eye drops in relieving dry eye after phacoemulsification. Medicine (Baltimore). 2021;100(25):e26358.
  13. Garrett Q, Simmons PA, Xu S, et al. Carboxymethylcellulose binds to human corneal epithelial cells and is a modulator of corneal epithelial wound healing. Invest Ophthalmol Vis Sci. 2007;48(4):1559-1567.
  14. Wysenbeek YS, Loya N, Ben Sira I, Ophir I, Ben Shaul Y. The effect of sodium hyaluronate on the corneal epithelium. An ultrastructural study. Invest Ophthalmol Vis Sci. 1988;29(2):194-199.
  15. Choi JH, Kim JH, Li Z, Oh HJ, Ahn KY, Yoon KC. Efficacy of the mineral oil and hyaluronic acid mixture eye drops in murine dry eye. Korean J Ophthalmol. 2015;29(2):131-137.
  16. Scifo C, Barabino S, De Pasquale G, Blanco AR, Mazzone MG, Rolando M. Effects of a new lipid tear substitute in a mouse model of dry eye. Cornea. 2010;29(7):802-806.
  17. Matsuo T, Tsuchida Y, Morimoto N. Trehalose eye drops in the treatment of dry eye syndrome. Ophthalmology. 2002;109(11):2024-2029.
  18. Ozek D, Kemer OE. Effect of the bioprotectant agent trehalose on corneal epithelial healing after corneal cross-linking for keratoconus. Arq Bras Oftalmol. 2018;81(6):505-509.
  19. Chen YZ, Chen ZY, Tang YJ, et al. Development of Lutein-Containing Eye Drops for the Treatment of Dry Eye Syndrome. Pharmaceutics. 2021;13(11):1801. Published Oct 27, 2021.
  20. Prabhasawat P, Ruangvaravate N, Tesavibul N, Thewthong M. Effect of 0.3% Hydroxypropyl Methylcellulose/Dextran Versus 0.18% Sodium Hyaluronate in the Treatment of Ocular Surface Disease in Glaucoma Patients: A Randomized, Double-Blind, and Controlled Study. J Ocul Pharmacol Ther. 2015;31(6):323-329.
  21. Oliverio GW, Spinella R, Postorino EI, Inferrera L, Aragona E, Aragona P. Safety and Tolerability of an Eye Drop Based on 0.6% Povidone-Iodine Nanoemulsion in Dry Eye Patients. J Ocul Pharmacol Ther. 2021;37(2):90-96.
  22. Garrigue JS, Amrane M, Faure MO, Holopainen JM, Tong L. Relevance of Lipid-Based Products in the Management of Dry Eye Disease. J Ocul Pharmacol Ther. 2017;33(9):647-661.
  23. Pinheiro MN Jr, dos Santos PM, dos Santos RC, Barros Jde N, Passos LF, Cardoso Neto J. Uso oral do óleo de linhaça (Linum usitatissimum) no tratamento do olhoseco de pacientesportadores da síndrome de Sjögren [Oral flaxseed oil (Linum usitatissimum) in the treatment for dry-eye Sjögren's syndrome patients]. Arq Bras Oftalmol. 2007;70(4):649-655.
  24. Higgins CL, Nixon RL. Periorbital Allergic Contact Dermatitis Caused by Lanolin in a Lubricating Eye Ointment. Australas J Dermatol. 2016;57(1):68-69.
  25. Om A, Yeung H, de la Feld S. Prevalence of Contact Allergens in Best-Selling Ophthalmic Products. Dermatitis. 2021;32(4):273-279.
  26. Aryasit O, Uthairat Y, Singha P, Horatanaruang O. Efficacy of baby shampoo and commercial eyelid cleanser in patients with meibomian gland dysfunction: A randomized controlled trial. Medicine (Baltimore). 2020;99(19):e20155.
  27. Jacobi C, Doan S, Pavel V, Chiambaretta F, Kärcher T. Different Approach to Manage Demodex Blepharitis - Initial and Maintenance Treatment. Curr Eye Res. 2022;47(3):352-360.
  28. Sung J, Wang MTM, Lee SH, et al. Randomized double-masked trial of eyelid cleansing treatments for blepharitis. Ocul Surf. 2018;16(1):77-83.
  29. Kemal M, Sümer Z, Toker MI, Erdoğan H, Topalkara A, Akbulut M. The Prevalence of Demodex folliculorum in blepharitis patients and the normal population. Ophthalmic Epidemiol. 2005;12(4):287-290.
  30. Koo H, Kim TH, Kim KW, Wee SW, Chun YS, Kim JC. Ocular surface discomfort and Demodex: effect of tea tree oil eyelid scrub in Demodex blepharitis. J Korean Med Sci. 2012;27(12):1574-1579.
  31. Gao YY, Di Pascuale MA, Li W, et al. In vitro and in vivo killing of ocular Demodex by tea tree oil. Br J Ophthalmol. 2005;89(11):1468-1473.
  32. Choi Y, Eom Y, Yoon EG, Song JS, Kim IH, Kim HM. Efficacy of Topical Ivermectin 1% in the Treatment of Demodex Blepharitis. Cornea. 2022;41(4):427-434.
  33. Tarsus. https://tarsusrx.com/pipeline/tp-03/ . Accessed March 9, 2023.
  34. Ngo W, Srinivasan S, Houtman D, Jones L. The relief of dry eye signs and symptoms using a combination of lubricants, lid hygiene and ocular nutraceuticals. J Optom. 2017;10(1):26-33.
  35. Oge' LK, Muncie HL, Phillips-Savoy AR. Rosacea: Diagnosis and Treatment. Am Fam Physician. 2015;92(3):187-196.
  36. Layton AM. Pharmacologic treatments for rosacea. Clin Dermatol. 2017;35(2):207-212.
  37. Nagymihályi A, Dikstein S, Tiffany JM. The influence of eyelid temperature on the delivery of meibomian oil. Exp Eye Res. 2004;78(3):367-370.
  38. Wladis EJ, Bradley EA, Bilyk JR, Yen MT, Mawn LA. Oral Antibiotics for Meibomian Gland-Related Ocular Surface Disease: A Report by the American Academy of Ophthalmology. Ophthalmology. 2016;123(3):492-496.
  39. Zhai J, Gu J, Yuan J, Chen J. Tacrolimus in the treatment of ocular diseases. BioDrugs. 2011;25(2):89-103.
  40. Dry Eye Assessment and Management Study Research Group, Asbell PA, Maguire MG, et al. n-3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease. N Engl J Med. 2018;378(18):1681-1690.
  41. Giannaccare G, Pellegrini M, Sebastiani S, et al. Efficacy of Omega-3 Fatty Acid Supplementation for Treatment of Dry Eye Disease: A Meta-Analysis of Randomized Clinical Trials. Cornea. 2019;38(5):565-573.
  42. Vernhardsdottir RR, Magno MS, Hynnekleiv L, et al. Antibiotic treatment for dry eye disease related to meibomian gland dysfunction and blepharitis - A review. Ocul Surf. 2022;26:211-221.
  43. Del Rosso JQ, Brantman S, Baldwin H. Long-term inflammatory rosacea management with subantibiotic dose oral doxycycline 40 mg modified-release capsules once daily. Dermatol Ther. 2022;35(1):e15180.
  44. Doxycycline hyclate vs monohydrate: which one is better for acne? https://miiskin.com/acne/medications/doxycycline-hyclate-vs-monohydrate/ . Accessed Feb. 15, 2023.
  45. Dohlman TH, Lertsuwanroj B, Ciralsky J. Management of Pediatric Blepharokeratoconjunctivitis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):986.
  46. Greene JB, Jeng BH, Fintelmann RE, Margolis TP. Oral azithromycin for the treatment of meibomitis. JAMA Ophthalmol. 2014;132(1):121-122.
  47. Utine CA. Update and critical appraisal of the use of topical azithromycin ophthalmic 1% (AzaSite) solution in the treatment of ocular infections. Clin Ophthalmol. 2011;5:801-809.
  48. Barnhorst DA Jr, Foster JA, Chern KC, Meisler DM. The efficacy of topical metronidazole in the treatment of ocular rosacea. Ophthalmology. 1996;103(11):1880-1883.
  49. O'Neil EC, Henderson M, Massaro-Giordano M, Bunya VY. Advances in dry eye disease treatment. Curr Opin Ophthalmol. 2019;30(3):166-178.
  50. Mukamal R. Improved Dry Eye Drugs for 2022 and Beyond. American Academy of Ophthalmology. 2021. https://www.aao.org/eye-health/tips-prevention/new-dry-eye-treatments-ocular-surface-disease . Accessed Feb. 15, 2023.
  51. Frampton JE. Varenicline Solution Nasal Spray: A Review in Dry Eye Disease. Drugs. 2022;82(14):1481-1488.
  52. Wirta D, Torkildsen GL, Boehmer B, et al. ONSET-1 Phase 2b Randomized Trial to Evaluate the Safety and Efficacy of OC-01 (Varenicline Solution) Nasal Spray on Signs and Symptoms of Dry Eye Disease. Cornea. 2022;41(10):1207-1216.
  53. Wirta D, Vollmer P, Paauw J, et al. Efficacy and Safety of OC-01 (Varenicline Solution) Nasal Spray on Signs and Symptoms of Dry Eye Disease: The ONSET-2 Phase 3 Randomized Trial. Ophthalmology. 2022;129(4):379-387.
  54. Lindgren ES, Cil O, Verkman AS, Pasricha ND. Ocular Surface Ion Transport and Dry Eye Disease. Curr Ophthalmol Rep. 2022;10(4):188-197.
  55. Burnouf T, Goubran HA, Chen TM, Ou KL, El-Ekiaby M, Radosevic M. Blood-derived biomaterials and platelet growth factors in regenerative medicine. Blood Rev. 2013;27(2):77-89.
  56. López-García JS, García-Lozano I, Rivas L, Martínez-Garchitorena J. Aplicaciones del suero autólogo en oftalmología [Use of autologous serum in ophthalmic practice]. Arch Soc Esp Oftalmol. 2007;82(1):9-20.
  57. Anitua E, Muruzabal F, Tayebba A, et al. Autologous serum and plasma rich in growth factors in ophthalmology: preclinical and clinical studies. Acta Ophthalmol. 2015;93(8):e605-e614.
  58. Drew VJ, Tseng CL, Seghatchian J, Burnouf T. Reflections on Dry Eye Syndrome Treatment: Therapeutic Role of Blood Products. Front Med (Lausanne). 2018;5:33. Published Feb 23, 2018.
  59. Shtein, RM, Shen, JF, Kuo, AN, Hammersmith, KM, Li, JY, Weikert, MP. Autologous Serum-Based Eye Drops for Treatment of Ocular Surface Disease OTA. American Academy of Ophthalmology. 2019. https://www.aao.org/ophthalmic-technology-assessment/autologous-serum-based-eye-drops-treatment-of-ocul . Accessed Feb. 15, 2023.
  60. Murri MS, Moshirfar M, Birdsong OC, Ronquillo YC, Ding Y, Hoopes PC. Amniotic membrane extract and eye drops: a review of literature and clinical application. Clin Ophthalmol. 2018;12:1105-1112. Published Jun 18, 2018.
  61. Pérez ML, Barreales S, Sabater-Cruz N, Martinez-Conesa EM, Vilarrodona A, Casaroli-Marano RP. Amniotic membrane extract eye drops: a new approach to severe ocular surface pathologies. Cell Tissue Bank. 2022;23(3):473-481.
  62. Weiner G. Update on Scleral Lenses. American Academy of Ophthalmology. 2018. https://www.aao.org/eyenet/article/update-on-scleral-lenses. Accessed Feb. 15, 2023.
  63. DeNaeyer G, Sanders DR. sMap3D Corneo-Scleral Topographer Repeatability in Scleral Lens Patients. Eye Contact Lens. 2018;44 Suppl 1:S259-S264.
  64. Harthan JS, Shorter E. Therapeutic uses of scleral contact lenses for ocular surface disease: patient selection and special considerations. Clin Optom (Auckl). 2018;10:65-74. Published Jul 11, 2018.
  65. BOSTONSIGHT PROSE. https://www.bostonsight.org/patients/patient-prose-treatment/ . Accessed Feb. 15, 2023.
  66. Bhattacharya P, Mahadevan R. Quality of life and handling experience with the PROSE device: an Indian scenario. Clin Exp Optom. 2017;100(6):710-717.
  67. Mukamal R. 12 Devices for Treating Dry Eyes. American Academy of Ophthalmology. 2020. https://www.aao.org/eye-health/tips-prevention/how-to-treat-dry-eye-devices . Accessed Feb. 15, 2023.
  68. EyePrintPro. https://eyeprintpro.com/process/ . Accessed Feb. 15, 2023.
  69. Nguyen MTB, Thakrar V, Chan CC. EyePrintPRO therapeutic scleral contact lens: indications and outcomes. Can J Ophthalmol. 2018;53(1):66-70.
  70. van der Worp E, Bornman D, Ferreira DL, Faria-Ribeiro M, Garcia-Porta N, González-Meijome JM. Modern scleral contact lenses: A review. Cont Lens Anterior Eye. 2014;37(4):240-250.
Ethan S. Lindgren, BS, is a staff research associate in the Department of Ophthalmology at the University of California San Francisco. Mr. Lindgren investigates novel pro-secretory therapies for DED. Email him at ethan.lindgren@ucsf.edu.

Ethan S. Lindgren, BS, is a staff research associate in the Department of Ophthalmology at the University of California San Francisco. Mr. Lindgren investigates novel pro-secretory therapies for DED. Email him at ethan.lindgren@ucsf.edu.

Neel D. Pasricha, MD, is an assistant professor of ophthalmology in the Cornea, External Disease and Refractive Surgery Division in the Department of Ophthalmology at the University of California San Francisco and Francis I. Proctor Foundation. Dr. Pasricha’s lab discovers and advances drug candidates to promote tear fluid secretion from ocular surface epithelial cells. Email him at neel.pasricha@ucsf.edu. Disclosure: Dr. Pasricha is a named inventor on patent applications on ocular surface potential difference measurements owned by the University of California San Francisco and is a consultant for Vanda Pharmaceuticals.

Neel D. Pasricha, MD, is an assistant professor of ophthalmology in the Cornea, External Disease and Refractive Surgery Division in the Department of Ophthalmology at the University of California San Francisco and Francis I. Proctor Foundation. Dr. Pasricha’s lab discovers and advances drug candidates to promote tear fluid secretion from ocular surface epithelial cells. Email him at neel.pasricha@ucsf.edu. Disclosure: Dr. Pasricha is a named inventor on patent applications on ocular surface potential difference measurements owned by the University of California San Francisco and is a consultant for Vanda Pharmaceuticals.

What to Read Next