At the completion of this article, the reader should improve their management of dry eye disease, including:
- Recognise the importance of personalised treatment strategies for DED patients, considering the
complexity of disease subtypes and individual variations in symptoms and responses to treatment - Evaluate the advantages of preservative-free eye drops in reducing adverse ocular surface effects and
improving outcomes in patients with DED - Understand how distinct subclassifications of DED necessitate different treatment approaches and the tailored use of aqueous-based versus lipid-based lubricating drops
Aidan Quinlan
BOptom (Hons), TPA Endorsed
Bay Eye Care, Tauranga, New Zealand
Optometrist AIDAN QUINLAN explains his own protocols for subclassifying dry eye, provides his own insights for accurate diagnosis and management, and highlights the benefits of preservative-free lubricating drops tailored to each patient’s symptoms.
In the complicated and conflicting world of dry eye disease (DED), the Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) reports serve as a pillar for clinical decision making. The group’s updated, internationally-recognised definition of DED was established in 2017: “Dry eye is a multifactorial disease of the ocular surface characterised by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.”1
Two important components of this definition stand out.
First, the multifactorial aspect of DED demonstrates a complex disease with varying aetiologies. It also alludes to the multitude of treatment modalities available. And second: homeostasis; which is defined as “a self-regulating process by which biological systems maintain stability while adjusting to changing external conditions”.2 With dry eye, the loss of homeostasis implies that the body has lost the ability to maintain a state of equilibrium. This results in tear hyperosmolarity, instability of the tear film and resulting associated sequelae (increased osmolarity, inflammation, neuropathy and reduced function).
Dry eye categories
The consensus in dry eye research and clinical practice has been established around two key diagnostic labels: 1) Evaporative DED, which is excessive evaporation of the tear film due to meibomian gland dysfunction (MGD); and 2) aqueous deficient dry eye (ADDE), which is reduced tear lacrimal gland production.
It’s generally accepted that rather than representing two separate categories, most patients suffer from a combination of both abnormal meibomian gland physiology which results in evaporative DED and tear underproduction which results in aqueous deficient DED.3
Estimates of overlap between the two groups span from 30% to 70%.3 One published research article found evaporative dry eye was three times more likely to be sub-classified compared to aqueous deficient dry eye. (Interestingly, over 30% of patients were found to have both types of DED).4
Case reports
Recognition of complexity is essential for management of DED. However, regardless of the underlying causes, appropriate daily lubricant eye drops play a critical role in managing dry eye symptoms and ocular health. The patients in the following case reports had different subclassifications of DED, each necessitating a distinct treatment approach, each reliant on lubrication drops, but of different classes.
While the first patient benefits from using a watery, aqueous-based drop, the second requires an oil-based, lipid drop. Each type of drop is crucial in improving hydration, nourishing the ocular surface and mimicking the natural meibum to improve tear stability. As these case reports show, NovaTears, Hylo Fresh and Hylo Forte were essential in relieving symptoms and improving the quality of life for these patients.
Case report 1
Mrs L* is a retiree with a love of painting and a caregiver of her husband and disabled daughter. She is bothered by constantly dry, sore and irritable eyes which are worse while painting or reading. Mrs L has a prior diagnosis of Sjögren’s syndrome. Her McMonnies questionnaire gave a score of 24 (suggestive of dry eye), and her OSDI survey score was 63/100 (suggesting severe dry eye). Unaided vision was reasonable in each eye at 6/7.5+.
Our initial overview photos (Figures 1 and 2) show diffuse conjunctival redness, lid margin telangiectasia, and a low Tear Meniscus Height (TMH). Measurement of TMH with Medmont Meridia showed R 0.13 mm and L 0.13 mm below the value of <0.2 mm that could be indicative of dysfunction of the lacrimal gland.5
An additional phenol red thread test (PRTT) agreed with the above finding. TearLab osmolarity testing results were R 330 mosmol/L and L 340 mosmol/L – well above the threshold for abnormal at >308 mOsm/L.6 It is important to remember that the magnitude of tear osmolarity is significantly correlated with dry eye signs as measured by corneal staining, conjunctival staining, TBUT and Schirmer’s test.7 This relationship is well documented in this case.
Non-Invasive Tear-Break Up Time (NIBUT) showed an almost constant disruption of placido rings with NIBUT for three to four seconds on both eyes. Corneae showed significant superficial punctate keratitis (SPK) and punctate epithelial erosions (PEE) staining with NaFl. It was largely distributed in the inferior half of cornea showing the impact of incomplete blinking habits and indicated possible nocturnal exposure during sleep.
With infrared meibography, Mrs L’s meibomian glands showed mild shortening and disorganisation. Meibum was flowing with mild cloudiness and thickness of deeper oils expressed with a two-pronged meibomian gland expressor.
Several issues contributed to the patient’s ocular surface disease:
• Moderate aqueous deficient DED because of decreased lacrimal gland function from underlying Sjögren’s syndrome;
• Mild meibomian gland dysfunction (severe due to the poor meibum quality and degree of lid margin inflammation) with secondary evaporative DED;
• Probable nocturnal ocular surface exposure, and;
• Poor blink technique
It’s vital to hone in on each component of the patient’s ocular surface disease for best symptomatic and clinical improvement.
• In order to manage her aqueous deficient dry eye and to improve lubrication and hydration, I inserted short-duration punctal plugs to retain vital aqueous in the eye.
• We tackled her meibomian gland dysfunction with the use of an anti-inflammatory dose of oral azithromycin tablets (500 mg on the first day, then 250 mg once a day for four more days). Research suggests azithromycin had a better clinical response when treating meibomian gland dysfunction compared to oral doxycycline, with fewer side-effects and a shorter course.8 Mrs L was also encouraged to take omega-3 supplements as they help improve meibomian gland function and decrease ocular inflammation.
• A sustained heat was applied across the glands for 10 minutes followed by gentle digital massage to further improve meibum flow and gland function. VitA-POS ointment applied into the lower fornix before sleep was prescribed to protect the eye from probable nocturnal exposure. In addition, blink exercises were used to improve blink technique and ensure complete blinks.
• Finally, I prescribed a non-preserved lubricating drop in the form of Hylo-Fresh (containing sodium hyaluronate 1 mg/mL).
Hylo-Fresh, containing the active ingredient sodium hyaluronate 1 mg/mL, is a great option for patients with aqueous deficient dry eye. Sodium hyaluronate is used in artificial tear supplements to increase viscosity and provide enhanced lubrication effects to the ocular surface. Several research studies have demonstrated its ability to bind to ocular surface cells and promote wound healing.3 HyloFresh and its alternative HyloForte (with sodium hyaluronate 2 mg/mL, leading to increased viscosity) are both preservative- and phosphate-free. I will touch on the importance of this on the next page.
Case report 2
Mr M* is a keen surfer that has trouble with sore, stinging eyes throughout the day that was exasperated from salt water. He also has a scratchy lower lid with misdirected lashes and history of left inferior lid melanoma removal. Mr M was currently using hydrating lubricating tears which he picked up at the local pharmacy and has used hot compressions for several months. The results from his OSDI questionnaire showed gritty and painful eyes all the time over the last week.
TearLab chemistry testing showed osmolarities of right 320 mosmol/L and L 334 mosmol/L. An abnormal reading in terms of magnitude and >8 mOsm/L difference between the two eyes.6
My anterior health assessment and ocular surface workup showed several causes of Mr M symptoms. Mr M’s left lower lid showed moderate trichasis with three to four lashes touching the inferior bulbar conjunctiva and cornea. He has moderate inferior SPK associated with the lashes. Assessment of the meibomian glands showed minimal meibum expressibility even with firm pressure with forceps indication hyposecretory meibomian gland dysfunction.
A main cause of this condition was revealed with infrared meibography with the Medmont Merida. It showed frank atrophy of 60-70% of inferior meibomian glands due to chronic dysfunction and prior surgery of the inferior left lid.
Several components are involved in Mr M’s ocular surface disease and help us understand some of his prior troubles with different management:
• Moderate hyposecretory meibomian gland dysfunction with 50-60% atrophy of glands L>R. In turn, leading to moderate evaporative DED.
• Inferior trichiasis L>R causing irritation, scratchiness and SPK on inferior cornea.
• A small indication of potential nocturnal ocular surface exposure causing morning irritation and soreness.
I find in these cases the best option is to begin with patient education and improving patient understanding of the ocular disease conditions. It can be helpful to use grading scales to further improve patient awareness of limitations to different management.
In this case, Mr M was educated regarding his meibomian gland atrophy and inferior lid trichiasis. He was able to understand why the left eye was more symptomatic than the right eye and many months of hot compressions were rather unhelpful for his overall condition. Although, due to lower rates of atrophy of the right and superior glands, an anti-inflammatory dose of oral azithromycin tablets (500 mg on the first day, then 250 mg once a day for four more days) was still used to improve remaining gland function.
The troublesome inferior left lashes were removed with fine tweezers and Mr M was instructed to return once they regrow for removal. He was educated on the option of electrolysis, which is a safe and effective process that uses a high-frequency electric current to destroy the hair follicle. VitApos ointment applied into the lower fornix before sleep will improve symptoms of nocturnal exposure.
I prescribed NovaTears, an oil-containing lubricating eye drop with active ingredient perfluorohexyloctane 100% v/v to be used four times a day. The efficacy and safety of perfluorohexyloctane ophthalmic solution in patients with dry eye due to meibomian gland dysfunction was assessed in the GOBI study.9 NovaTears demonstrated statistically significant and clinically meaningful improvements in the signs and symptoms of DED. Several other studies have also shown improvements in tear stability, corneal staining, and OSDI scores with perfluorohexyloctane containing lubrication drops.10
A key aspect to prescribing lubricating drops in these cases – and in part all DED cases – is considering the use of preservatives. Several preservatives are used in ophthalmic preparations for DED, the most common and widely studied in benzalkonium chloride (BAK). BAK has been shown to cause disruption of tear stability, cellular damage of both the corneal and conjunctival epithelium, and induce inflammatory changes on the ocular surface.10
Other studies of symptomatic ocular surface disease where patients were switched from preserved to preservative-free treatments showed astounding results. Incidence of irritation, burning, dry eye and foreign body sensation, tearing and itching reduced by two-thirds, with the incidence of conjunctival hyperaemia, staining, and blepharitis dropping by half.10 In some cases, patients can be apprehensive to switch to preservative-free topical lubricates due to preservative-free preparations being supplied in single-dose units leading to handling issues, increased cost and increased packing waste.
Products such as HyloFresh and HyloForte come in specialised multi-dose bottles which make preservative-free sterility possible. It is the unique COMOD multi-dose application system which adjusts airflow and prevents the solution from coming into contact at any time with the surrounding air eliminating the potential for contamination. It means that patients such as Mrs M can confidently use these drops frequently to nourish the ocular surface and improve symptoms without adverse effects of preservatives.
Mr M, on the other hand, is using a lubricating drop with a semifluorinated alkane medium which bacteria cannot live in. It means that preservative-free NovaTears is ideal for regular use. NovaTears is suitable for patients like Mr M where significant improvement in the underlying disease mechanism is not expected due to the dense atrophy of meibomian glands.
Patient education about the targeted use of drops such as NovaTears which stabilise their tear-film is helpful. In this case, I instructed Mr M to insert drops before going out for a surf, on cold mornings or prior to a walk in windy weather. It is important that patients know about the smaller volume drop of NovaTears and the ‘warm’ or ‘soft’ feel of the low-surface tension drop when it hits the eye – vastly different to the drops they may have previously been using.
An often complex and varied condition, DED can be tackled using a rational and well-reasoned series of assessments. Hopefully this article aids in making the diagnosis of your patient’s condition(s) more straight-forward, improves your management discussions and leads to appropriate treatment and management strategies. In a quest for patient satisfaction and positive ocular health outcomes.
*Patient names changed for anonymity.
NOTE: The author received a monetary honorarium from AFT Pharmaceuticals for providing this article.
More reading
Optometrists going back to the future on dry eye disease
What space travel teaches us about dry eye
An Australian ophthalmologist’s take on low light level therapy for dry eye
References
1.Jennifer P Craig 1, Kelly K Nichols 2, Esen K Akpek et al. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017; 15 (3): 276-283. doi: 10.1016/j.jtos.2017.05.008.
2. Billman GE. Homeostasis: The Underappreciated and Far Too Often Ignored Central Organizing Principle of Physiology. Front Physiol. 2020 Mar 10; 11: 200. doi: 10.3389/fphys.2020.00200.
3. Jones L, Downie LE, Korb D, Benitez-Del-Castillo JM, Dana R, Deng SX, Dong PN, Geerling G, Hida RY, Liu Y, Seo KY, Tauber J, Wakamatsu TH, Xu J, Wolffsohn JS, Craig JP. TFOS DEWS II Management and Therapy Report. Ocul Surf. 2017; 15 (3): 575-628. doi: 10.1016/j.jtos.2017.05.006.
4. Lemp MA, Crews LA, Bron AJ, Foulks GN, Sullivan BD. Cornea 2012;31(5):472e8.
5. Arita, R., Itoh, K., Maeda, S., et al., Efficacy of diagnostic criteria for the differential diagnosis between obstructive meibomian gland dysfunction and aqueous deficiency dry eye. Jpn J Ophthalmol. 2010; 54 (5), 387–391 DOI: 10.1007/s10384-010-0858-1.
6. Wolffsohn JS, Arita R, Chalmers R, et al. TFOS DEWS II diagnostic methodology report. Ocul Surf. 2017; 15: 539–574.
7. Greiner JV, Ying GS, Pistilli M, Maguire MG, Asbell PA; Dry Eye Assessment and Management (DREAM) Study Research Group. Association of Tear Osmolarity with Signs and Symptoms of Dry Eye Disease in the Dry Eye Assessment and Management (DREAM) Study. Invest Ophthalmol Vis Sci. 2023; 64 (1) :5
8. Kashkouli, M.B., Fazel, A.J., Kiavash, V., et al, Oral azithromycin versus doxycycline in meibomian gland dysfunction: a randomised double-masked open-label clinical trial. Br J Ophthalmol. 2015; 99 (2): 199–204. DOI: doi.org/10.1136/bjophthalmol-2014-305410.
9. Tauber J, Berdy GJ, Wirta DL, et al, GOBI Study Group. NOV03 for Dry Eye Disease Associated with Meibomian Gland Dysfunction: Results of the Randomized Phase 3 GOBI Study. Ophthalmology. 2023; 130 (5): 516-524.
10. Walsh K, Jones L. The use of preservatives in dry eye drops. Clin Ophthalmol. 2019; 13: 1409-1425.
