Since the Dry Eye Workshop’s 2007 definition of dry eye disease (DED)¹ became public, it has become common parlance to discuss the disease as a multifactorial condition. However, it is far less common for ophthalmologists to treat DED in accord with a multifactorial strategy. Most physicians are comfortable with a pharmacologic, anti-inflammatory approach, including prescription drops and Omega-3 supplementation, yet display a reluctance to incorporate alternate methods of anti-inflammatory control, such as devices.

Why should there be reluctance on the part of ophthalmologists to apply anti-inflammatory modalities of therapy to DED beyond pharmacology? Multiple-modal therapy is already occurring in the setting of glaucoma in which physicians accept three general strategies to lower IOP — pharmacology, the use of lasers and surgery. As part of a comprehensive approach to treating DED, perhaps it is time to emulate our approach to glaucoma, and expand our offerings to include devices as an integral part of the strategy.

BORROWING FROM DERMATOLOGY

When many of us chose a career in ophthalmology, we understood that, in many ways, we would remain isolated from our colleagues in other fields of medicine. Most physicians outside of eye care received little training in ophthalmology, cannot: perform a basic eye exam; use any ophthalmic equipment, understand a hand-written ophthalmology consult; decipher what we even mean by “OD” and “OS”. Thus we often find ourselves on a metaphoric medical island. However, perhaps we can build bridges to our colleagues in other fields of medicine, via DED, and in particular, dermatology.

Historically, perhaps the most well-known synergy between ophthalmology and dermatology was the application of botulinum toxin, previously used for strabismus and blepharospasm, for the treatment of forehead lines and wrinkles. An equally significant overlap is the connection between facial rosacea and meibomian gland disease. An 85% association has been identified between the two conditions.² Intense pulsed light (IPL) has been used by dermatology for many years as an effective method of treating facial rosacea. Is there a lesson for ophthalmology?

IPL, EXPLAINED

IPL is a treatment that uses broad-based light, mostly within the visible spectrum, that has been filtered to allow only select wavelengths to pass into tissues. The wavelengths have been chosen to interact with target chromophores. For example, in the setting of IPL use for the removal of unwanted skin pigmentation, the target chromophore is melanin. In the setting of meibomian gland disease, the target is oxyhemoglobin, a molecule present within the endothelial cells of the telengectatic vessels that characterize MGD. By selectively absorbing the wavelengths of filtered light, the targeted blood vessels may be coagulated, thereby reducing their leaky contribution of inflammatory mediators to the ocular surface. MGD has been found to occur in 86% of DED patients.³ By improving the inflammatory nature of the lid disease, we may be simultaneously improving the inflammatory DED state as well.

Numerous other mechanisms of action are under consideration to harness the efficacy of IPL in treating ocular surface disease — one example is photomodulation, the process by which light in the visible and infrared portions of the electromagnetic spectrum induces intracellular changes.⁴ In this context, electron transport chain activity within mitochondria may be enhanced by improving cellular ATP levels and increasing Ca ion influx. This could improve production of the protein collagen, which is vital for vascular function.⁵

Furthermore, evidence exists that IPL might be an effective way to eradicate Demodex. It is well-known that Demodex flourish in the setting of rosacea, possibly due to the perivascular edema common in rosacea that creates a Demodex-favorable environment. The pigmented exoskeleton of Demodex appears to absorb the energy of IPL leading to their destruction.⁶

IPL may exert its effect through other mechanisms including the modulation of both pro- and anti-inflammatory molecules. In skin fibroblasts, IPL has been demonstrated to reduce MMP levels.⁷ Finally, early evidence suggests IPL may modify reactive oxidative species, potentially providing yet another explanation for IPL’s effects.⁸

A growing body of evidence exists within the peer-reviewed literature validating the efficacy of IPL treatments. In 2015, a prospective, placebo-controlled study demonstrated statistically significant improvements in tear film quality and symptoms by 45 days after treatment.⁹ In a separate, 3-year retrospective study, 68 of 78 patients showed improved tear-breakup time while 93% of patients reported satisfaction post-treatment.¹⁰

In 2016, a multicenter study demonstrated significant improvements in lid margin edema and vascularity, facial telangiectasia, meibum viscosity and oil flow. Overall, no serious adverse events were reported in any of these studies.¹¹

THE LOGISTICS OF IPL

One unique advantage of treating DED patients with IPL is the ease-of-use this technology provides for doctors as well as the ease-of-treatment for patients. In general, a series of four to six treatments, separated by a month, are recommended for patients, with each treatment taking 10 minutes or less. Patients are advised to avoid exposure to the sun immediately following their treatment but, otherwise, have no additional restrictions. Patients with higher levels of skin pigmentation (Fitzpatrick level 4 or higher) should be advised to avoid IPL due to the risk of pigmentation changes.

In my practice, metallic, laser-grade corneal shields are inserted under the eyelids, after which the periocular region is treated, including the lid margins. Patients experience minimal discomfort; minimal erythema is noted immediately following treatment. Meibomiam gland expression may be performed following treatment, but does not appear to be mandatory. Mostly, meibomiam gland expression provides diagnostic value as a metric to measure improvement in meibum quality from treatment to treatment.

We are using the Lumenis M22 with Optima IPL system. It offers a few potential advantages. The device’s optimal pulse technology ensures an even, homogenous delivery of energy with each pulse. It has a contact cooling tip, providing greater comfort to the patient. Furthermore, the device offers two different sized tips, including a small tip, perfect for the contours of the peri-ocular region. The system also comes with interchangeable wavelength filters to allow the operator to treat varied facial lesions, such as cherry hemangiomas and sun spots.

WHY DEVICES?

Like glaucoma patients who often require multiple modalities of treatment, so too do our DED patients. Devices such as IPL offer an alternate anti-inflammatory option to pharmacology and neutraceuticals. With devices, we find a drug-free option that avoids unwanted side effects, drug-drug interactions and systemic contraindications. IPL can be used as an adjunct to other treatments, becoming part of a comprehensive strategy to treat a multifactorial disease. Alternately, IPL can be used as an effective strategy in recalcitrant DED, nonresponsive to traditional therapies. It can be efficiently administered by the doctor, providing a unique opportunity to expand the quality of the doctor-patient relationship, a component of DED management often overlooked. And, finally, as a noncovered procedure, IPL offers providers the chance to drive additional cash revenue into a highly prevalent disease state. For those interested in innovation and business development, IPL should be on your A-list. OM

REFERENCES

1. 2007 Report of Dry Eye Disease Workshop, TFOS
2. Viso et al., 2014. Rosacea-associated Meibomian Gland Dysfunction= An Epidemiological Perspective. European Ophthalmic Review, 2014;8:13–16.
3. Lemp MA, Crews LA, Bron AJ, Foulks GN, Sullivan BD. Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study. Cornea. 2012;31:472-478.
4. Karu T. Primary and secondary mechanisms of action of visible to near IR radiation on cells. J Photochem Photobiol B. 1999; 49:1-17.
5. Takezaki S et al. Ultrastructural observations of human skin following visible red light-emitting diodes: a preliminary in vivo report. Laser Ther 2005; 14:153-160.
6. Kirn T. Intense pulsed light eradicates demodex mites. Skin and Allergy News. 2002; 33:37.
7. Wong WR et al. Intensed pulsed light modulates the expression of MMP-2, MMP-14, and TIMP-2 in skin dermal fibroblasts cultured within contracted collagen lattices. J Dermatol Sci. 2008; 51:70-73.
8. Lan C et al. LED 590 nm photomodulation reduces UVA-induced metalloproteinase-1 expression via upregulation of antioxidant enzyme catalase. J Dermatol Sci. 2015; 78; 125-32.
9. Craig JP, Chen YH, Turnbull PR. Prospective trial of intense pulsed light for the treatment of meibomian gland dysfunction. Invest Ophthalmol Vis Sci. 2015 Feb 12;56:1965-1970.
10. Toyos R, McGill W, Briscoe D. Intense pulsed light treatment for dry eye disease due to meibomian gland dysfunction; a 3-year retrospective study. Photomed Laser Surg. 2015 Jan;33:41-46.
11. Gupta PK, Vora GK, Matossian C, Kim M, Stinnett S. Outcomes of intense pulsed light therapy for treatment of evaporative dry eye disease. Can J Ophthalmol. 2016 Aug;51:249-253.

About the Author

Dr. Adler is the director of Ophthalmology at the Belcara Health Premier Multi-Specialty Center in Baltimore, Md. He is an assistant professor of Ophthalmology at the Wilmer Eye Institute. Dr. Adler received his medical degree at the Johns Hopkins School of Medicine and completed both his ophthalmology residency and cornea fellowship at Wilmer.

Disclosures: Dr. Adler is a consultant to Allergan, Lumenis and Topcon.