Increased steps – up to 10,000 steps a day – is the panacea to a better, healthier, and longer life. Science and medicine say so.1
But do the humans that possess the concern, motivation, and discipline to execute this daily routine also incorporate healthier eating, minimise stress, and perform weight-bearing exercises?
if the patient presents with additional signs and symptoms of allergy, it is clinically reasonable to initiate concurrent allergy treatment prior to considering other medium- to long-term DED measures
It stands to reason that there must be some overlap that compounds the 10,000-step mantra.
To paraphrase Sherlock Holmes, as he examined a case with his partner and confidant Dr Watson, “It’s not that elementary”.
The term ‘overlap’ is what I consider whenever a dry eye patient consults me for the first time.
History taking is the key. Is there an overlap with the medicines the patient has been prescribed that may contribute to dry eyes?
Is there an overlap with a co-morbidity, such as rosacea or thyroid disease, that may impact the anterior eye surface?2,3
Is it possible that the patient has a vitamin deficiency? A 2023 review by Rolando and Barabino even suggests that because of its positive effect in modulating the immune and inflammatory response, the systemic supplementation of vitamin D should be considered as a potentially effective therapeutic strategy in dry eye disease (DED).4
And critically, is there a dry eye overlap with allergy? Is the patient experiencing ‘itchy’ eyes in conjunction with their other dry eye symptoms?
Is there a history of eye rubbing, particularly in younger patients? After all, there is strong evidence of an increased risk factor for keratoconus with ‘eye-rubbers’.5,6
From here the history may extend to asking the patient if they have a known allergy to seasonal pollens, dust mites, pets, etc. Often they will respond inconclusively because they have never been investigated for these possibilities.
Objective examination may display signs of allergy, such as conjunctival chemosis and superior tarsal plate papillae.7 Patients with a mixed pathophysiology of DED and allergy usually do not display unequivocal signs of vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), or giant papillary conjunctivitis (GPC). Instead, their signs resemble features corresponding to seasonal allergic conjunctivitis (SAC) (Figure 1).8,9
Figure 1. Seasonal allergic conjunctivitis: Image Mark Roth.
Initial Therapies
Lubricants are the initial therapy for DED, as described by the TFOS DEWS II Report,10 and by nature, they also help with conjunctival and epithelial allergy.
However, if the patient presents with additional signs and symptoms of allergy, it is clinically reasonable to initiate concurrent allergy treatment prior to considering other medium- to long-term DED measures, such as oral tetracyclines, macrolides, punctual plugs, or intense pulsed light therapy.
The primary mediators of allergy in the eye are mast cells. Estimates of the number of mast cells in the human eye vary, but there is general agreement that there are more than 50 million and most are located closer to the conjunctival surface. As the eyes do not have the same protective barriers as other structures in the human body, the eyes are a common location for the allergic response.
After sensitisation and activation by an allergen, mast cells degranulate (Figure 2) and release histamine, chemotactic factors, and a diversity of other pro-inflammatory mediators. Apart from immunotherapy and / or avoidance of the potential allergen, ocular therapy targets histamine and other mediators released by mast cells (Figure 3).
Figure 2. Pathway inducing allergic mast cell degranulation.
Figure 3. Mast cell allergic cascade and management /treatment options. Modified by Mark Roth.
A coherent, methodical treatment plan may include the following:
Step One
Avoid any oral antihistamines.
Most of these medications, particularly the earlier generation of antihistamine drugs, can contribute to dry eyes by decreasing tear film production and quality.11
Step Two
Prescribe a lubricant of your choice, at least four times a day.
There is no clear evidence that one lubricant is significantly more effective than another. Frequency of dosing sometimes appears to be more significant than the lubricant selection itself. Ultimately, after multiple selections of eye drops, patient feedback and preference can dictate the selection.
Without any proprietary interests, my current go-to lubricants are Cationorm and Blink; both are preservative free. For very mild symptoms, I generally start with Blink, four times a day, and reduce that dosage as per examination review and changes to the patient’s symptomatology. Blink contains hyaluronate, which in my view is an undervalued feature.
For greater than mild signs and symptoms, particularly if there is corneal epithelial punctate staining, I prescribe Cationorm emulsion. This lubricant is excellent because of its optimum viscosity and surface tension.
Additionally, there is good evidence that its hypotonic tonicity confers some osmocorrection, which can be beneficial in restoration of ocular surface homeostasis, and hence beneficial for re-epithelialisation and long-term management of DED.12
A DED questionnaire, such as the Ocular Surface Disease Index (OSDI)13 or the Standard Patient Evaluation of Eye Dryness (SPEED),14 may be useful for consideration of effectivity of treatment and/or dosage adjustments.
The Oculus Keratograph 5M is an advanced corneal topographer with a colour camera optimised for external imaging. Using the software, it is possible to grade the degree of conjunctival injection. The dry eye examination protocol includes a questionnaire and additional features that include examining the meibomian glands and non-invasive tear film break-up time, measuring the tear meniscus height, and evaluating the lipid layer.
These are all relevant features to help differentiate different forms of dry eye,10 and to highlight factors that are consistent with allergy.
Step Three
Prescribe antihistamine eye drops concurrently with lubricants.
It is quite uncommon to prescribe an H1-antihistamine eye drop alone.
More effectively, the drug of choice is a dual acting antihistamine and mast cell stabiliser. The antihistamine works rapidly to reduce symptoms of itching while the mast cell stabiliser works to prevent symptoms for a longer period of time. The available agents in Australia are Ketotifen (Zaditen) and Olopatadine (Patanol), prescribed twice a day. Both are excellent choices and again, there is no clear evidence that one is superior to the other.15
Step Four
Prescribe a topical steroid for manifest ocular surface inflammation.
The late phase of the allergic conjunctivitis cascade involves the synthesis of leukotrienes, prostaglandins, cytokines, and other chemotactic mediators.
If a patient has signs of significant conjunctival chemosis, and/or features related to limbal or corneal inflammation, and significant upper tarsal plate papillae, a short pulse dose of a topical steroid will do what antihistamines and lubricants cannot.
From a pathophysiological perspective, the pro-inflammatory mediators released by mast cells require an anti-inflammatory agent to quell the allergic cascade or the inflammatory component of DED.10 Flurometholone alcohol (FML) is an appropriate selection, but my preference is flurometholone acetate (Flarex), as it reduces the inflammation far more rapidly and has better penetration for conjunctival papillae. Using a more effective anti-inflammatory can shorten the overall treatment time of a steroid and eventually allow any other agents to work more effectively. Because it is a pulse dose, (e.g., every two hours on the first day, then four times a day for seven to 10 days) no dose tapering is required. However, it is not uncommon to leave the patient on one or two drops a day while other drugs have time to reach their therapeutic concentrations.
The use of steroids in this manner is incredibly safe and in the best interests of the symptomatic patient. The cumulative pulse dose of topical eye drop steroids is negligible in terms of potential for cataracts.
A regular intraocular pressure (IOP) check is mandatory if taking steroids for longer than one week. Topical steroids do not cause glaucoma. They are only a risk factor for ocular hypertension which, if left undiagnosed, can lead to progressive optic neuropathy, glaucoma. Regular IOP checks prevent that possible scenario.
Step Five
For longer term treatment, consider ciclosporin A.
It is generally accepted that ciclosporin A is an important ‘steroid-sparing’ immunomodulating drug for DED.10 It also has great efficacy in the setting of allergic eye disease, which makes it an ideal agent when DED and allergy exist concurrently. Ciclosporin A works by inhibiting t-cells by preventing their activation. Additionally, ciclosporin A stimulates lacrimal gland tear production and inhibits histamine release. If moderate signs and symptoms exist, it is common clinical practice to pulse dose with topical steroids followed by a longer therapy of ciclosporin A in conjunction with other treatments. Ikervis and Cequa are the two commercially-based drugs that are available without compounding. Their mechanism of action is similar, but Ikervis is a cationic emulsion, which has all the benefits consistent with Cationorm.16 This means the patient may experience less sting and greater comfort. Ikervis also has the advantage of once-a-day dosing. In mild-to-moderate dry eye and ocular allergy, the patient may not qualify for a Pharmaceutical Benefits Scheme (PBS) subsidy for these drugs, however it should not be excluded as an option due to costs without discussing advantages and disadvantages with the patient first. There are many examples in general health prescribing where a patient agrees to a non-PBS drug based on their symptomatology. Ciclosporin A has no side effects related to cataracts and IOP, which facilitates a great safety profile for long-term use.
Step Six
Prescribe nasal sprays.
Long-standing evidence suggests that nasal allergy treatments applied topically to the nose may positively affect ocular allergy symptoms. The parasympathetic nasal-ocular neural reflex pathway is involved in the stimulation of allergic responses in the eye.17,18
Interestingly, nasal spray treatment was shown to reduce symptoms more in the evening than in the morning.19 Additionally, a different study showed that a combination nasal steroid-antihistamine was more effective than either agent alone. Nasal spray agents can be accessed by patients as S3 drugs ‘over the counter’, however providing a patient with a prescription tends to avoid confusion and aid compliance.
Many brands of intranasal preparations are available in Australia. Olopatadine has a rapid onset of action. As with oral antihistamines, intranasal antihistamines (INAHs) target the H1-receptor, but olopatadine also has a dual action of inhibiting mast cell degranulation.18
Intranasal corticosteroids, such as beclomethasone (Beconase), have excellent anti-inflammatory properties that reduce symptoms of sneezing, itching, rhinorrhea, and congestion. It can also reduce allergic eye symptoms, such as itching, tearing, and redness via the parasympathetic pathway.19
In summary, it would be reasonable to prescribe an antihistamine nasal spray once a day in the morning and a steroid nasal spray once a day in the evening.
Step Seven
Consider a referral to a private or public allergist.
A consultation with an allergist may be of great long-term benefit. Specific allergens to that patient may be identified and hence allergy immunotherapy (AIT) becomes an option. AIT, also known as allergen desensitisation, is a method to develop a state of tolerance to an agent responsible for an allergic or hypersensitive reaction.20
Clinical Tips
Punctate Epithelial Staining
At times a particular eye drop, or a combination of drops, may result in conjunctival or corneal compromise. Wherever possible, use preservative free drops. Review the patient’s compliance and frequency of drops used, to ensure they are not using more drops than the prescribed recommendation.
Consider reviewing the medications without compromising your diagnosis or the requirements of that particular agent. Additional lubricants before and after medicated drops, but not at same time, may be helpful.
Treating Children
The Australian Medicines Handbook (AMH) suggests children over 12 years of age are eligible for the same dosage as adults. For younger patients, suitability and contraindications should be assessed using one of the many reference guides to medicines, such as the AMH, MIMS or Australian Prescriber.
Drugs During Pregnancy
Because the evidence on drugs used in pregnancy is unclear, my default position is to avoid medications wherever possible.
For the duration of the pregnancy, the patient may be more symptomatic than with optimised therapy. Copious lubricating eye drops and saline nasal sprays like Fess may be the best option. Fess is a non-medicated saline solution that facilitates nasal passage moisture and can help clear excess mucus and allergens.22 However, each patient needs to be assessed individually and some harmacotherapy may be required. In these cases, communication with the patient’s general practitioner and their obstetrics and gynaecology specialists is essential.
Conclusion
Patients who present with concurrent allergy and dry eyes can be challenging to treat.
This is an opportunity to be flexible according to the patient’s needs, and to use a wide variety of treatment options. Often the patient will have consulted multiple practitioners and randomly used, or been prescribed, multiple eye drops with no significant or prolonged improvement. Patients will be grateful for the time and expertise spent on managing their dry eye and allergy disease with a strategic plan to achieve an optimum range of agents to improve their eyes and quality of life.
Associate Professor Mark Roth FAAO OAM BSc Pharmacology (Monash University) BAppSc Optometry (Queensland University of Technology) also has a Post Graduate Diploma in Ocular Therapeutics (New England College of Optometry, Boston), and a Graduate Certificate of Education (The University of Melbourne). He practises as a clinical optometrist in Armadale, Victoria. He is a Clinical Associate Professor at The University of Melbourne and a Fellow of the American Academy of Optometry.
Declaration of interest: Nil
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