Saturday, November 9, 2024

Dry eye: Patient identification, product formulation and therapy escalation

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At the completion of this article, the reader should be able to improve their management of patients requiring treatment for dry eye disease (DED), including:

  • Understand what a dry eye patient looks like, and how DED is often a combination of physical symptoms and environmental conditions, including recreational activities, that can lead to DED and/or exacerbation of the condition
  • Understand what to look for in terms of management options and how formulation matters when it comes to suitability for the ocular surface
  • Understand when and how to elevate DED treatment if artificial tears are not enough • Understand and manage DED patient expectations.

 

 

Image: Leigh Plowman.

Leigh Plowman
Optometrist
Otway Optical, Colac, Victoria

LEIGH PLOWMAN explores dry eye disease from a patient-identification perspective, discussing management options and highlighting the role of immunomodulators like topical ciclosporin in treatment escalation.

Dry eye disease (DED) is a common condition worldwide, with estimates ranging from 5% to 50% of the population, depending on location.1 It’s a complex, multifactorial disease related to disrupted tear film homeostasis accompanied by ocular symptoms such as itch, blurring and discomfort.2 In addition to its complex pathophysiology, DED can be a symptom of numerous diseases, and can also be a consequence of systemic medications.

Making matters more complex, DED is commonly self-treated, often sub-optimally, before the sufferer presents to an eyecare professional. This delay in professional diagnosis and treatment can have a significant impact on patient outcomes, including patient mental health.3

Once diagnosed, determining the optimal management for each individual patient can also be difficult. In this article, we will explore DED from a patient-identification perspective, offer advice on the management options available, identify when and how to escalate treatment, and explore a case study to provide a practical example of the treatment of DED.

Figure 1: Sequential pathway for the diagnosis of DED. Based on the findings of TFOS DEWS II.4

Identifying a DED patient:
Signs and symptoms

The Tear Film and Ocular Surface Society (TFOS) launched the Dry Eye Workshop II (DEWS II) in 2015, bringing together 150 of the world’s foremost experts in the field of dry eye. Their objective: to provide a deeper understanding of DED and how to treat it.

As a result of this massive undertaking, the seminal TFOS DEWS II report was published, offering practical advice and an algorithm to aid with patient identification.4 Essentially, the TFOS DEWS II report explains that diagnosis of DED depends on a sequence of three areas of investigation following the presentation of a patient with a dry eye complaint:

1.  triaging questions to determine differential diagnosis and potential comorbidities (and exclude conditions that can mimic DED)

2. risk factor analysis to determine likelihood of DED

3. diagnostic tests to confirm (Figure 1)

Triaging Questions

The TFOS DEWS II Diagnostic Methodology Report5 details the types of triaging questions that should be asked, and the basis for them, but in general, it’s important to explore the nature of the signs and symptoms presented to understand the likelihood of DED. For instance: assessing the presence, and level or duration, of pain may uncover underlying trauma, infection or ulceration that could explain symptoms that otherwise may be deemed to be DED. Knowing the types of questions to ask, and how to investigate the responses to them, will do a lot of the initial heavy lifting when trying to diagnose DED.

Risk Factor Analysis

Once satisfied that the symptoms presented are likely due to DED, the next step is to examine the patient’s risk factor profile. Broadly speaking, the risk factors can be broken into two groups: non-modifiable risk factors – such as age and gender – and modifiable risk factors, which include lifestyle, environment and current medications.

Knowing the risk factors – women are significantly more prone to suffering from DED than men, for example6 – can again go a long way in confirming the presence of DED before any testing is even done.

Figure 2: Diagnostic tests for DED and the baseline results required to determine the presence of DED. Based on the findings of TFOS DEWS II.7

Diagnostic Tests

The final step, according to TFOS DEWS II, in diagnosing DED is the use of validated diagnostic tests. These tests take the form of both quantitative and qualitative methodologies that, together, can confirm a diagnosis of DED. Qualitative tests include the validated DEQ-5 (Dry Eye Questionnaire) and OSDI (Ocular Surface Disease Index) questionnaires, while quantitative options include Ocular Surface Staining (OSS) and Tear Break Up Time (TBUT). An example of the criteria for each of these tests is in Figure 2.

Treatment options for DED

Treatment follows diagnosis, of course, and the options available will depend on numerous factors, including DED subtype, the presence of inflammation, severity and impact of disease and past treatments.

Subtypes of DED

There are three types of DED, each requiring a different approach to treatment.

• Evaporative dry eye (EDE), characterised by excessive evaporation from the tear film

• Aqueous-deficient dry eye (ADDE), characterised by reduced secretion of tears

• Mixed dry eye (MDE), a combination of both EDE and ADDE2

While 86% of patients with DED suffer from increased evaporation,8 it is important to address all layers of the tear film, which will have a significant bearing on the initial choice of product used to treat DED, namely artificial tears.

Non-inflamed DED and Artificial tears

Artificial tears (ATs) have been the mainstay for the treatment of DED because they have the capacity to treat the key physiological issues of DED: increased evaporation and reduced tear secretion, or hydration of the ocular surface.1

Careful and diligent use of ATs can break the deleterious cycle of DED and prevent exacerbation of the condition or further damage of the ocular surface, but key to this is determining the correct choice of AT for the subset of DED.

Not all artificial tears are the same; some may be oil-based and lack an aqueous component, which will be suitable for EDE but does nothing to address the lack of hydration. Conversely, a water-based product may effectively hydrate the ocular surface but may be short-lived if there is no oil component to sit on top of the eye and prevent or reduce evaporation.

Which artificial tear?

Choosing the right type of AT – especially in such a crowded market – can be tricky, but a simple maxim that may help with this is: consider the formulation. Understanding the necessary features of an AT (namely that it addresses all layers of the tear film) can come from knowing, in very basic terms, the key components in the formulation:

• Does the AT contain a lipid layer stabiliser? (Hyaluronic acid products, for example, often do not).

• Is water and/or hydrating ingredients such as glycerin present?

• Does the formulation interact with the ocular surface in such a way that it will prolong contact time, without increasing viscosity and compromising patient acceptability?

• Is the formulation positively-charged? This important point is often overlooked. The ocular surface is negatively charged, so a positively-charged formulation has the best chance at remaining on the ocular surface by way of simple electrostatic attraction.

dry eyedry eye
Figure 3: PBS eligibility criteria for prescribing Ikervis (0.1% CsA). Please refer to PBS Schedule for full information. Image: CSL Seqirus.

Escalating therapy for DED

While ATs have the capacity to effectively treat DED, the presence of underlying pathologies such as inflammation often necessitates an escalation in therapy; in the case of inflammation to an anti-inflammatory agent such as topical ciclosporin (CsA).

Knowing when and how to escalate therapy can be tricky; TFOS DEWS II in their four-step DED treatment algorithm recommend topical CsA as a step two option to consider when step one treatment options such as ATs, lifestyle modification and lid hygiene are insufficient.5

Ikervis, a 0.1% CsA, for example is available in Australia and can be prescribed by optometrists and ophthalmologists for the treatment of severe keratitis in adult patients with DED which has not improved despite treatment with ATs. Crucially, there is no universal, clinical definition of severe keratitis and the decision to prescribe relies on the prescriber’s clinical judgement considering both signs (CFS grade), as well as symptoms (impact of DED on quality-of-life).

This is a particularly important point and should hopefully help when prescribers need to ascertain whether escalation to CsA is warranted. Ikervis is available to be prescribed as a PBS authority item for patients who meet specific CFS and OSDI requirements (Figure 3) and can be prescribed privately for patients who do not meet the PBS criteria.

A patient’s dry eye journey

Every individual experiencing dry eye has a distinct narrative and journey, influenced by a variety of factors such as their overall health, medication regimens, environmental conditions and lifestyle.

‘Ben’* first presented to Otway Optical in Colac, Melbourne, in 2018 complaining of a sore right eye following an injury with a fire curtain. He had a central traumatic epithelial defect in the right eye and used eye ointments overnight.

Ben had three episodes of recurrent corneal erosion (RCE) until early 2022. As such, he started using a bandage contact lens alongside a hyaluronic acid artificial tear.

Ben returned to the clinic in May of 2023 complaining that the right eye often felt gravelly overnight, gritty upon waking, and dry during the day. While RCE was an underlying issue, it was clear that there was also something else contributing to these signs and symptoms.

dry eyedry eye
Figure 4: Nasal lissamine staining of Ben’s eyes before and after treatment with Cationorm and Ikervis. Images: Leigh Plowman.

Using the TFOS DEWS II algorithm, Ben was first asked triaging questions to determine his history followed by a risk factor analysis.He had a history of dry nose and mouth, hay fever, anterior blepharitis, conjunctivochalasis, ocular rosacea and meibomian gland dysfunction, and he was taking systemic medications for reflux, arthritis and an anti-depressant, the latter of which may have been the cause of the dry nose and mouth.

Further, Ben is a volunteer with the CFA as a bushfire instructor, renovates homes in his community, and is a target shooter. These risk factors, combined with his history, meant that dry eye was likely. His DEQ-5 score was 12 while TBUT was less than 10 seconds, confirming the diagnosis according to TFOS DEWS II Diagnosis Criteria. Ben was then started on Cationorm eye drops, prescribed to instil every three hours.

Within two weeks, Ben felt that his eyes had improved a little yet were still a little dry overnight. Digging deeper, I found that Ben had mild lissamine staining, indicating aqueous-deficient dry eye, but the fact that his dry eye symptoms hadn’t improved adequately with an AT told me that keratitis was an issue.

This was the pivotal moment in Ben’s treatment, and it was clear that treatment needed to be escalated to an immunomodulator. While Ben did not meet the specific criteria for PBS, Ikervis was prescribed privately every evening, alongside Cationorm four times a day.

The key to ensuring compliance with treatment was to educate Ben on the journey; irritation is likely when CsA is being used to treat keratitis, but this is common and usually temporary, and the fact that CsA can be used consistently without the need to limit treatment time (as with steroids) means that treatment can have a lasting positive impact. Managing expectations with patients is one of the most crucial components of successful treatment.

By June of 2023, Bens DEQ-5 score had dropped to 9, there was a significant improvement in his nasal lissamine staining and conjunctival hyperaemia (Figure 4), he hadn’t experienced dryness, grating or gravelly sensations, and had been doing what he loved (renovating and target shooting) without issue. In Ben’s words, “my eyes have never felt so comfortable”.

Summary

As this experience in the clinic shows, it’s hard to overstate the importance of a comprehensive approach to dry eye management – including proper diagnosis, risk factor analysis and patient education.

Ben’s case demonstrates how escalating treatment to include an immunomodulator, alongside appropriate counselling, led to significant improvement in his symptoms and quality-of-life.

By sharing these clinical experiences, I hope to offer some insights into the complexity of dry eye and the importance of individualised treatment plans

Ultimately, when a patient is diagnosed with dry eye, a responsibility emerges for the eye care provider, as well as the patient, which requires a dedication to the ongoing monitoring of the condition, and the willingness to adjust the treatment strategies when or if those conditions change. 

*Name changed to protect patient confidentiality

NOTE: This article was developed with the support of CSL Seqirus.

More reading

Considerations for low-dose atropine for myopia control in a non-Asian population

Insights from an Australian gonioscopy workshop – Part 2

Gonioscopy primer: Insights from a gonioscopy workshop (Part 1)

References
1. Stapleton F, Alves M, Bunya VY, Jalbert I, Lekhanont K, Malet F, Na KS, Schaumberg D, Uchino M, Vehof J et al (2017). TFOS DEWS II Epidemiology Report. Ocul Surf. 15 (3): 334–365. doi: 10.1016/j.jtos.2017.05.003.
2. Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK et al (2017). TFOS DEWS II Definition and Classification Report. Ocul Surf. 15 (3): 276-283. doi: 10.1016/j.jtos.2017.05.008.
3. He Q, Chen Z, Xie C, Liu L, Yang H, Wei R (2022). Relationship Between Dry Eye Disease and Emotional Disorder: The Mediating Effect of Health Anxiety. Front Public Health. 10: 771554. doi: 10.3389/fpubh.2022.771554.
4. Craig JP, Nelson JD, Azar DT, Belmonte C, Bron AJ, Chauhan SK et al (2017). TFOS DEWS II Report Executive Summary. Ocul Surf. 15 (4): 802-812. doi.org/10.1016/j.jtos.2017.08.003
5. Wolffshon JS, Arita R, Chalmers R, Djalilian A, Dogru M, Dumbleton K et al (2017). TFOS DEWS II Diagnostic Methodology Report. Ocul Surf. 15 (3): 539-574. doi: 10.1016/j.jtos.2017.05.001.
6. Matossian C, McDonald M, Donaldson KE, Nichols KK, MacIver S, Gupta PK (2019). Dry Eye Disease: Consideration for Women’s Health. J Womens Health (Larchmt). 28 (4): 502-514. doi: 10.1089/jwh.2018.7041
7. Craig JP, Nelson JD, Azar DT, Belmonte C, Bron AJ, Chauhan SK et al (2017). TFOS DEWS II Report Executive Summary. Ocul Surf. 15 (4): 802-812. doi.org/10.1016/j.jtos.2017.08.003
8. Lemp MA, Crews LA, Bron AJ, Foulks GN, Sullivan BD (2012). Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study. Cornea. 31 (5): 472-478. doi: 10.1097/ICO.0b013e318225415a

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