At the completion of this CPD activity, optometrists will understand the clinical aspects of managing dry eye disease. Including:
- Developed a structured approach to dry eye disease
- Appropriately triage the most likely cause of dry eye for each, unique patient
- Understand the value of technology to image the eyes and document many facets of a patient’s eyes and tear film
- Recognise the need to implement a combination of therapies to address the multi-factorial causes of each individual case
of dry eye disease.
The new standard of care for dry eye requires a multifactorial approach – and it’s complicated. Tasmanian optometrist MARTIN ROBINSON’s dry eye strategy involves embracing the complexity of the disease and adopting a structured approach so he can go beyond symptom-management to address the underlying causes of each unique presentation.
Martin Robinson
BApp Sc(Optom)
Optometrist and Principal Owner, Martin’s Eyecare, Hobart, TAS
State President of the Cornea and Contact Lens Society of Australia TAS (CCLSA)
National Vice President CCLSA
It has been almost five years since the Tear Film and Ocular Surface Society (TFOS) released its Dry Eye Workshop II (DEWS II) report which included an updated internationally-recognised definition of Dry Eye Disease (DED): “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
Clinically, the signs of DED are often poorly correlated with symptoms, and studies have shown more than 40% of subjects showing positive signs of DED are actually asymptomatic.2
BEISTO
The key word in the TFOS’s definition of dry eye disease is “multifactorial”. It’s instructive to explore some practical cases and see how a structured approach to the multifactorial causes of DED can elicit a diagnosis and treatment path.
In the following examples, we will go through detailed examinations, drawing on ‘BEISTO’, a concept first coined by dry eye pioneer Dr Laura Periman. That is: Bugs/Bacteria, Enzymes, Inflammation, Statis, Temperature and Obstruction. When a sign of any of these BIESTO impediments is found, a different treatment pathway is required.
Case 1
A 69-year-old post-menopausal Caucasian female presented who had several pairs of spectacles made in the last nine months and was unhappy with all of them. Her case history revealed she was a retired from a long career of clerical paperwork and computer work – 40 hours a week for 40 years in air-conditioned offices.
She suffered from Crohn’s, Colitis, reactive airways dysfunction syndrome (RADS) and fibromyalgia. Twelve months before she presented at our clinic, she had a skin cancer removed from her nose bridge which was treated with a topical chemotherapy cream after removal. In this patient’s case history, there are many areas of possible influence of DED. Among them:
• Inflammatory bowel disease (IBD) including Crohn’s and Colitis. Ocular manifestations for IBD include iritis, episcleritis, optic neuritis, blepharitis and DED. Of these, blepharitis and DED are reported at rates of 24.6% and 57.4%, respectively. Reduced tear volume is the most reported sign.3
• RADS is associated with increased incidence of steroid-induced cataract.
• Fibromyalgia can cause dryness of the eyes and mouth, most associated with ocular pain.
• Chemotherapy often causes dry mouth and dry eyes; this is due, in part, to stem cell damage. Fast replicating stem cells like those in salivary glands, meibomian glands and limbal stem cells are often impacted. Meibomian gland shortening, obstruction and complete atrophy are all reported with systemic and topical chemotherapy.
• Changes to estrogen and androgens can cause DED.
• Administration and computer use can lead to poor blink habits, including incomplete blinking and more rapid blinking.
Examining the patient in a structured way can help to appropriately triage the most likely causes. I perform a Full Jenvis Pro dry eye exam using the Oculus Keratograph K5 device. This aides me in my diagnosis pathway.
Detailed photo/video documentation of this nature at initial examination is helpful to set a baseline to document any improvements or adverse events (AEs) after treatment. In addition, it is invaluable as a teaching tool to show patients DED signs and prove to them that behaviours such as incomplete blinking are present.
List of findings from initial keratography assessment
• Jenvis Pro examinations delivers a total score out of 100, with a lower score being abnormal. This patient’s scores were, OD: 40; OS:37. Ocular surface disease index score: 60 OSDI is scored out of 100 with the higher number being more symptomatic, above 13 is abnormal.
- With the Jenvis Pro report, I find most people are satisfied when they score above 65 so for this patient we need a 40-60% improvement. WRT OSDI a 30% reduction is considered successful intervention, so we would aim for 40.
• Refraction was unstable, with especial trouble determining astigmatism axis and power.
• No symptoms of Posterior Subcapsular Cataract (PSCC), no iritis, no age-related macular degeneration (AMD) and no episcleritis were seen.
• Tear meniscus was normal and no dry mouth symptoms.
• No ocular pain was reported.
• Incomplete blinking was moderate with 20-30% of the cornea surface impacted.
• Blink rate was severe at over 20 blinks a minute. Normal for women is 12-14, so almost double.
• Non-invasive tear break up time (NITBUT) was reduced. It was shorter in the left eye than in the right eye (L>R).
• Meibomian gland shortening and drop-out seen worse nasally in both eyes.
• Lid margin uneven with capped MGs and excess lid biofilm present, but lashes were clean.
• Conjunctiva chemosed, injected and with some conjunctival chalasisalisis but very limited staining of the conjunctiva, and nil seen on the cornea.
• OSDI severe at 60. But areas of effect were all visual and wind/AC intolerant.
From the initial keratography findings, RADS is not a likely contributor. And as there is no ocular pain and tear volume is normal, fibromyalgia is also unlikely.
The patient’s lashes are clear with no collarettes, but she does have meibomian gland dysfunction so IBD could be a cause. However, her symptoms started 12 months ago, and her IBD is long standing. (10% of people that suffer IBD will experience eye problems in their life, so it is a prudent question to ask when you take the patient’s case history).
The patient’s years of working in offices with computers are likely contributors to the abnormal blinking rate and the incomplete blinking. Her MG changes could be age-related, menopause-induced or computer-use influenced. The nasal drop out could be caused though the topical chemotherapy use. The conjunctival changes are influenced by the abnormal lid margin combined with the increased blink rate. And the answers she provided to the OSDI questionnaire suggest an unstable normal volume tear film and leads us to a primary diagnosis of evaporative dry eye.
Treatments prescribed
• Manual lid debridement is indicated to remove the biofilm and clear abnormal epithelial overgrowth of the meibomian glands.
• Avenova hypochlorous acid spray once daily. Hypochlorous acid is useful to reduce the bacterial load on the eyelids, a common cause of the biofilm when makeup is not used.
• Blink training, including slow blinking – close, pause, pause, open, relax. Conjunctival chalasis is partly inflammatory and partly friction caused. If the patient can make full, complete blinks, we can reduce the number of blinks a day, reducing the friction. In addition, full closed eye blinks allow the meibomian gland acini to open, releasing oils.
• Lumenis M22 Intense Pulse Light (IPL) treatment. Four sessions to the periorbital region using the Epstein protocol, avoiding the bridge of the nose where the skin cancer was removed.
- IPL reduces the inflammation seen around the eyelids by eliminating pro-inflammatory blood vessels. Additionally, IPL pulses are photo bio-modulators, able to stimulate the stem cells of the meibomian glands and create smaller, healthier and more active acini.
• After the final IPL session, a Blephasteam and Mastrota eyelid expression will be performed. I prefer to clear any obstructions to meibomian glands with heat and expression, but only after the inflammation is reduced, this reduces the amount of pressure needed to clear the glands, resulting in a more comfortable procedure. In addition, I prefer to do a lid debridement first before performing Mastrota expression, again to allow more efficient clearance and reduce and discomfort.
Results
The combination of lid debridement, Avenova and blink training worked well. The patient reported an 80% reduction in symptoms in the first week.
We arranged a repeat refraction and new spectacles, and the patient is very happy. A dry eye success without eye drops. Historically we might have tried artificial tears, and these alone would have been unlikely to help in this case.
Discussion
I did not prescribe any eyedrops in this case, rather, I followed the signs and symptoms and explored the possible contributors. IBD is possibly a contributor, as are bacteria, her age and sex and her blink habits, but the timeline indicates a specific tipping point where homeostasis was lost. This occurred after the nose skin cancer treatment with topical chemotherapy.
Chemotherapy reduces acini, reduces stem cell activity, and causes meibomian gland atrophy. The significant loss of her nasal meibomian glands matches this hypothesis. A detailed examination led to a structured treatment plan and an elimination of her symptoms.
Case 2
A 24-year-old Caucasian male presented on the advice of his dermatologist for a dry eye examination. He had been prescribed Roaccutane for bad acne nine months prior, and his dry eye symptoms started within the first few weeks. The symptoms steadily worsened, and he had seen another optometrist who prescribed Optimel 16% eye drops which he was using a few times a day, but they caused significant pain and did not seem to help much.
He described significant light sensitivity most of the time, but worst at night. Air conditioning was unbearable. Psychologically, he was stressed and frightened. A recent graduate from university, he was about to start his first job in a week, and he was frightened that he would not cope. The areas of preliminary diagnosis in his case are as follows:
• Optimel 16% eye drops are a recognised, effective treatment for signs and symptoms of DED.4 In studies the adverse events are listed as sting and increased injection after instillation, for a short time. This patient reports significant pain and no reduction in his signs or symptoms over some time.
• Acne vulgaris, the condition diagnosed and treated by his dermatologist is a possible cause of the DED. Both acne vulgaris and meibomian glands are influenced by androgenic hormone and strongly correlate with ocular dryness.
• Roaccutane – active ingredient isotretinoin is well documented in being the cause of significantly higher risk of ocular adverse events (AEs), even in the year after treatment cessation. These AEs include blepharoconjunctivitis, keratoconjunctivitis sicca, cutaneous photosensitivity and contact lens intolerance. In fact, Isotretinoin seems to inhibit the ability of the meibomian acinar cells to differentiate, while simultaneously stimulating the epithelial lining the ducts and acini to proliferate. 5
• Certain medications are known to cause photosensitivity.
The Jenvis Pro dry eye report and full eye examination revealed the following:
• OD 65 score OS 44, score OSDI 31.
• Patient and his girlfriend both deny any redness or irritation prior to starting Roaccutane, making acne vulgaris an unlikely cause.
• Excessive froth seen on his lid margins, and floating in the tear film indicating excess bacterial flora.
• Lid margin telangiectasia, meibomian glands capped and obstructed with no expression seen.
• Meibomian gland scan showed no shortening of glands but very pale ‘ghost like’ appearance
• Incomplete blinking severe >33% of eye not covered.
• OSDI 31 with light sensitivity, soreness and pain, and wind/AC intolerance worst results.
• NITBUT above average, no breakup seen in first test. Test repeated with a fan blowing in the room, NITBUT reduced to seven to eight seconds.
• Inferior staining on conjunctiva, nil staining on cornea
Diagnosis
From the findings we can safely eliminate simple pre-existing MGD from acne vulgaris, no evidence of any prior signs or symptoms. The level of reported pain from Optimel made me uncomfortable, combined with no apparent changes in signs or symptoms and inferior staining, I advised him to cease using it. He reported no other medications apart from the Roaccutane.
The most likely hypothesis is the isotretinoin has caused his current conditions and the appearance of the eyelids, meibomian gland scans, and other tests indicate a reduction in function and obstruction of at least the outer ducts of the meibomian glands. Isotretinoin has been demonstrated to cause a significant time and dose dependent effect on both the morphology and the proliferation of meibomian glands.
Treatment
• Cease Optimel, start Systane Hydration, a better lubricant for the rough lid margins and should help with the inferior staining.
• Blink training, slow blinking as in case 1 to develop improved blink behaviour.
• Ocusoft Hypochlor spray 1/day after a shower to reduce bacterial flora.
• Lumenis M22 IPL for four sessions to periorbital region using the Epstein protocol for 1st session, to reduce the inflammation
• Lid debridement after 1st IPL to remove the biofilm scurf.
• At second IPL, add additional Eyelid IPL using Cox2 metal shields and following the Periman Protocol for eyelids. This is done at lowest fluence and for three pulses per eyelid using a small crystal, for a double pass. This was due to the severe lid inflammation which I felt required more intense treatment.
Results
Systane Hydration gave immediate improvement over Optimel with improved comfort and longer lasting relief, in addition there was no staining. The Hypochlor spray eliminated all froth, his blinking was slower and more complete. His eye redness was greatly reduced, the lid margins were also less injected and less thickened.
The meibomian glands have regained structure, definition and their production of meibum was restored, now easy to express with gentle pressure. He was no longer light sensitive, day or night, his stress levels were reported as significantly reduced, and he displayed what I would describe as a return to a self-confident young man. His use of Systane Hydration continued but only on random days where he had put in long hours on the computer.
Take home message
DED is a nuanced condition, multifactorial and complex. We can no longer take a simplistic view of DED, either in its diagnosis or treatment. Its inherent complexity requires multifactorial solutions. We all can do more when it comes to case histories, examinations, and diagnoses.
Our evolving understanding of DED has precipitated an escalation of the use of technology to treat the condition. I feel that technology is not only helpful, but essential to correctly document many facets of a patient’s eyes and tear film. And in many cases, only technology can offer the solutions needed to address the patient’s symptoms of DED.’
I urge all practising eyecare providers to rethink their approach to DED. It will help their practice, improve their bottom line and most importantly, provide the best outcomes for their patients.
SIDEBAR: Cosmetics as a contributing cause of DED
The presence of DED strongly correlates to our patient’s levels of stress, their mental health, and self-esteem; it also affects females more than males. In the past we have been quick to blame hormones for this sex-linked discrepancy, but recent studies have started looking at beauty products, make-up, cosmetics, lotions and wipes, their ingredients, and their impact on the ocular surface.
Cosmetics all contain preservatives; this is essential to limit the growth of bacteria and funguses in cosmetics. However, many preservatives used like benzalkonium chloride, and formaldehyde (FA)-releasing preservatives are toxic to the ocular surface. FA releasing chemicals are also present in many adhesives used to apply the ever more popular eyelash extensions. Studies have shown the dose-dependent effects of these chemicals on MGs, corneal and conjunctival cells, and there is concern about longer term cumulative dose impacts.7
If a patient is using make-up, or lash extensions or skin care products in general, this may add several layers of complexity to a DED assessment.
References
- Jennifer P Craig 1, Kelly K Nichols 2, Esen K Akpek et al. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017 Jul;15(3):276-283. doi: 10.1016/j.jtos.2017.05.008. Epub 2017 Jul 20.
- Bron AJ, Tomlinson A, Foulks GN, Pepose JS, Baudouin C, Geerling G, Nichols KK, Lemp MA. Rethinking dry eye disease: a perspective on clinical implications. Ocul Surf. 2014 Apr;12(2 Suppl):S1-31. doi: 10.1016/j.jtos.2014.02.002. Epub 2014 Feb 13. PMID: 24725379.
- Lee HJ, Song HJ, Jeong JH, Kim HU, Boo SJ, Na SY. Ophthalmologic manifestations in patients with inflammatory bowel disease. Intest Res. 2017;15(3):380-387. doi:10.5217/ir.2017.15.3.380
- Li AL, Li SL, Kam KW, et al Randomised assessor-masked trial evaluating topical manuka honey (Optimel) in treatment of meibomian gland dysfunction. British Journal of Ophthalmology Published Online First: 08 January 2021. doi: 10.1136/bjophthalmol-2020-317506
- Neudorfer M, Goldshtein I, Shamai-Lubovitz O, Chodick G, Dadon Y, Shalev V. Ocular Adverse Effects of Systemic Treatment With Isotretinoin. Arch Dermatol. 2012; 148 (7): 803–808. doi:10.1001/archdermatol.2012.352
- Juan Ding, Wendy Kam, David Sullivan; Influence of Isotretinoin on Human Meibomian Gland Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2012; 53 (14): 598.
- Xiaomin Chen, David A. Sullivan, Amy Gallant Sullivan, Wendy R. Kam, Yang Liu. Toxicity of cosmetic preservatives on human ocular surface and adnexal cells, Experimental Eye Research, Volume 170, 2018, Pages 188-197, ISSN 0014-4835, https://doi.org/10.1016/j.exer.2018.02.020.
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