Intense pulsed light (IPL) therapy

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Intense pulsed light (IPL) therapy is a relatively new treatment for evaporative dry eye and rosacea.

Using filters in the IPL handpiece, the light spectrum emitted from the flash lamp can be absorbed by oxyhemoglobin. The light is converted to heat-inducing ablation of vascular structures. This process of photothermolysis is one of the proposed mechanisms of action of IPL for dry eye wavelengths to selectively destroy blood vessels by targeting chromophores within the blood vessels. The destruction of telangiectasias along the eyelid inhibits access of inflammatory mediators to the meibomian glands. Other potential mechanisms include a mild local warming effect to allow better expression of meibum and destruction of bacteria that cause inflammation at the level of the meibomian glands.

IPL emits pulsed light at a wavelength in the range 500 – 1200 nm, selecting the spectrum through a cutoff. Longer wavelengths (1000 nm) penetrate more deeply and can be used for telangiectasias situated deeper in the dermis and for large vessels. Lower cutoff filters (500 to 600 nm) effectively treat smaller-caliber vessels but interact more readily with epidermal and dermal melanin. Therefore shorter wavelength filters should be reserved for treating fair-skinned individuals (Fitzpatrick skin phototypes I – II). Energy densities must be set appropriate to the lesion to treat. Larger vessels require more energy to heat up, and smaller vessels heat more quickly, requiring fluences ranging from 25 – 45 J/cm2. Pulses are delivered as single, double or triple pulses; each pulse lasting 2 – 25 ms for larger vessels and 2.5 – 5 ms for smaller vessels. Longer pulse widths are gentler, while shorter bursts of energy produce a stronger reaction. The pulse duration (generally between 0.5 – 88.5 ms) lower than the thermal relaxation time of the target structures may spare the surrounding tissue from excess heating. Different intervals between pulses range within 10 – 500 ms; the delay between pulses allows the non-target tissues to cool down while the heat is retained in the target of interest[1]. The micro pulses allow the epidermis cells and smaller vessels to cool down between pulses. At the same time, the heat is retained in the larger vessels, resulting in selective thermal damage[2].

IPL is used to treat facial skin damage, including wrinkles, coarseness, laxity, and dyspigmentation[3]. IPL increases the synthesis of collagen I and III, procollagen, collagenase, and elastin and increased hyaluronate receptor expression, thus supporting the role of IPL in dermal collagen remodeling and improving skin texture[4]. The reduction in the mechanical integrity of the upper dermal connective tissue is related to rosacea, allowing a passive dilation of the vasculature manifesting as erythema and telangiectasia, and extravascular leakage of inflammatory mediators causing inflammatory papules and pustules[5]. IPL improves rosacea by ablating these abnormal vessels and might also improve the dermal connective tissue disorganization and elastosis by the process of collagen remodeling. This would improve the vascular component of rosacea (erythema and telangiectasia), possibly followed by a reduction in the appearance of inflammatory lesions. It is also plausible that collagen remodeling is responsible for the longevity of the effects induced by IPL[5].

Treatment procedure

IPL treatment uses a wavelength band range from 550 to 1200 nm. The intensity of the treatment may be adjusted to 10 J/cm2, on a contact surface of cool Sapphire, 48 x13 mm (6.2 cm2), representing an energy density of 62 Joules in each flash. The parameters of the number of micropulses, size, and the time interval between them in each flash may be adjusted according to the degree of skin pigmentation.

The procedure begins protecting the eye with opaque goggles and applying ultrasound gel on the patient's periocular area, eyelids (canthal to canthal), and the facial cheek area to spread the energy conduct the light providing a high degree of protection and efficacy. The IPL treatment is carried out in two steps into the periocular area, and the cheek area:

  • For the periocular area, 6 flashes are applied in each eye as shown in the left image 3 flashes on the skin of the lower eyelid (position 1) and 3 flashes on the canthal area (position 2), taking care to avoid overlap the same area alternating each flash between positions 1 and 2.
  • For the cheek area, 8 flashes on the skin of the four positions showed in the right image from position 1 to 4, also avoiding overlap the same area, and repeating once again from 1 to 4 position.


IPL treatment zones, where the handpiece is applied on the skin
IPL treatment A1.png IPL treatment A2.png IPL treatment B2.png IPL treatment B1.png
Periocular area Cheek area


The same procedure is performed on the other side of the face. At the end of each session, the protective goggles and gel are removed.

The mechanical expression of the Meibomian glands may be performed. With the patient sitting on the slit lamp and using a cotton swab, the meibomian glands ofthe lower and upper eyelids weresqueezing toward the eyelid margin, until the mebium release was visualized.

Finally, sun protection cream is applied to avoid exposure to the sun for the first 48 hours. The subjects may receive four separate treatment sessions, the first day (D1), after 14 days (D14), after 28 days (D28), and after 49 days (D49). The room temperature and relative humidity may be stable during treatments 22± 0.5 ºC and of 60±3%, respectively.

Meibomian gland dysfunction

Introduction

Meibomian gland dysfunction (MGD) is a common condition associated with Dry eye disease (DED), representing the leading cause of the evaporative component. MGD increases the DED severity with a clinically adverse impact on patient's life quality[6]. The prevalence of MGD varies geographically and by age, with reports of 5%–20% in Western countries to 45%–70% in Asiatic[7].

The pathogenesis of MGD and DED has been described as a vicious cycle in which inflammation is the essential factor[7]. MGD is triggered by different factors (skin disorders, eyelid inflammation, and microbial infections), resulting in ductal epithelium hyperkeratinization and increased meibum viscosity. The glandular ductus is filled with degenerate and viscous meibum, which contains keratinized cellular material accumulating inside the glands (intraglandular cystic dilatation), resulting in its atrophy[8]9. As a consequence, the lower outflow of the meibum induces the proliferation of commensal bacteria[9], releasing fatty acids and mono and diglycerides into the tear film, provoking more inflammation and irritation of the ocular surface[10]. The result is the instability of the tear film exposing the corneal surface, with the subepithelial nerve plexus and more inflammation[11] triggering the vicious DED cycle that would feedback the MGD cycle.

Different treatments have been proposed; the use of preservative-free artificial tears, anti-inflammatories, and cyclosporine; antibiotics to control the ocular surface microbiota or the presence of Demodex; dietary supplements with Omega-3 fatty acids to improve the lipid composition of the meibomian glands and tear film; warm compresses, and lid hygiene; radiofrequency to decrease the viscosity of the meibum, mechanical expression of the Meibomian glands, and intraductal probing[12]. The truth is that no one achieves a fully effective long-term improvement.Intense pulsed light (IPL) can successfully treat DED symptoms and signsby decreasing symptoms due to MGD, tear film abnormality, and tear inflammatory markers[13].

IPL mechanism of action

IPL benefits dry eye, improving the dysfunction of the meibomian glands[14][15][16][17][18][19][13].

The exact IPL mechanism is unknown. At present, various effects have been proposed trying to explain this technology. The most important are:

  1. warming the meibomian glands to facilitate the expression and release of the meibum inside[20];
  2. improving the function of the Meibomian glands[21];
  3. inducing intravascular thrombosis of the small blood vessels surrounding the Meibomian glands and telangiectasia of the eyelid margin, reducing the levels of proinflammatory mediators that contribute to dry eye[13][14];
  4. reducing tear osmolarity, helping to control the inflammation of the ocular surface, which is one of the key factors in dry eye pathogenesis[14][22][17];
  5. reducing the load of Demodex mites that stimulate secondary inflammation[23];
  6. improving cellular functions such as collagen synthesis, fibroblasts regeneration, and motility in immunoregulatory cells[24][25];
  7. inducing a neurotrophic effect on the cornea and ocular surface and a neuroimmunomodulatory effect on the meibomian glands[26][27].

Evidence

Toyos[14] treated with IPL showing improvement of DED symptomatology in 93% of cases and clinical signs in 87%. Vora and Gupta[28] reported improvement of lid margin edema, in the meibum quality score, and found a significant increase in the oil flow score and tear film break-up time, and a decrease in ocular surface disease index scoring. Craig et al[29] demonstrated that IPL alone was effective in improving the lipid layer and patient symptoms. Vegunta et al.[16] showed that the combination of IPL and MG expression improved dry eye symptoms in 89% of patients, and meibomian gland function in 77% of patients. Arita et al[30] showed the combination of IPL and Meibomian gland expression (MGX), improving homeostasis of the tear film and ameliorating ocular symptoms in patients with refractory MGD, compared with a control group with MGX alone. Karaca et al[31]referred amelioration of symptoms just 2 hours after the IPL and speculated with a neurological effect of the IPL. Cheng and Xue[32][22] referred good results after IPL treatment showing the improvement related to the microstructures of the meibomian glands with in vivo non-invasive confocal microscopy (INICM).

Rosacea

Introduction

Rosacea is a common chronic skin disease on the central face, affecting cheeks, nose, chin, and forehead[33]. Manifestations include persistent facial erythema, papules, pustules, telangiectasia, and repetitive flushing. For the rosacea diagnosis, at least one of the primary features must be present on the face: flushing (transient erythema), nontransient erythema, papules and pustules, and telangiectasia. Secondary features may appear, including burning sensation, dry appearance of the skin, edema, ocular manifestations, phymatous changes, or different location other than the face[34]. It can present phymatous changes through hypertrophy of the sebaceous glands and fibrosis, the most common of which is rhinophyma[33]. The earliest clinical presentation of vascular rosacea is a recurring blush, followed by erythema, which becomes constant, and eventually telangiectasias[33].

Rosacea is classified into 4 subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular rosacea[34]: Ocular rosacea, affecting the eyes, is estimated to occur in up to three-quarters of patients with rosacea, and frequently produces a foreign-body sensation, dryness, burning, itching, redness, photophobia, tearing, and blurred vision[35]. Signs include blepharitis, meibomitis, keratitis, corneal neovascularization, and ulceration[35]. The spectrum of presentation varies from mild to severe, affecting any age group, typically most severe in the 30 to 50 years, being women more commonly affected than men[36]. It is characterized by episodes of exacerbation and remission. The prevalence ranges from 1% to 22% depending on the definition and population characteristics[36].

The pathophysiology of rosacea remains unclear, appearing involved in genetic factors, dysregulation of the immune system, vascular and neuronal dysfunction, and microorganisms, especially Demodex folliculorum. Triggers factors may exacerbate the symptomatology, such as heat, stress, ultraviolet light, wind, spicy food, hot beverages, smoking, alcohol,oral contraceptive pills or other hormonal influences, and corticosteroids[37]. The skin barrier is affected in rosacea, resulting in excessive transepidermal water loss, making the skin dry, inclined to scaling and peeling, and sensible to burning and stinging[38]Flushing and erythema are vascular elements representing an increased number of erythrocytes in inflamed vessels. Chronic extravascular fluid accumulation in the superficial dermis causes damage to the lymphatic vessels and subsequent edema. Besides, neutrophil elastase released at the site of inflammation degrades the extracellular matrix and Type IV collagen in the capillary walls reducing the integrity of blood vessels[39]. Reduction in the integrity of the dermal connective tissue allows passive dilation of the vasculature, causing the telangiectatic component[40].

There are many treatment options for rosacea, such as topical metronidazole, azelaic acid cream, and non-irritating benzoyl peroxide; or systemic oral antibiotics, including tetracyclines, doxycycline, and minocycline. However, there are needs for other alternatives because of antibiotic resistance, irritation after the use of topic treatments[36], and the unlikely reduction of telangiectasia and centrofacial erythema[41][42]. Intense pulsed light (IPL) can successfully treat the clinical manifestations of rosacea that fail to respond to medical therapies, resolving telangiectasia and erythema[43]. IPL is a relatively new technology that has been developed for treating vascular and pigmented lesions. It emits polychromatic light in millisecond pulse duration for delivering selective energy to target blood vessels[44], which is the target of rosacea treatment[45]. IPL has shown benefits treating facial rosacea, especially by improving the dysfunction of the meibomian glands and dry eye that these patients usually present[14][15][16][17][18][19][13]. The clinical improvement gets reflected by a decrease in symptoms due to MGD, tear film abnormality, and tear inflammatory markers[13].

Rosacea affects the physical aspect and can have critical psychosocial impacts, with a loss of self-confidence and distress in social or work circumstances. Patients with rosacea have higher rates of depression, anxiety, and decreased self-esteem[46][47][48][49][50].

IPL mechanism of action

IPL benefits rosacea improving the dysfunction of the meibomian glands and dry eye[14][15][16][17][18][19][13], and clearing telangiectasia, and reducing erythema[5][24][34][44][51][52].

The exact IPL mechanism is unknown. At present, various effects have been proposed trying to explain this technology. The mechanisms of action of the IPL is considered by a mixed effect on the inflammatory status, and in the microcirculation of the skin:

  1. Inflammatory status: patients with DED present high inflammatory molecules in tears and on the ocular surface[13][53]. IPL has the potential to interfere with this inflammatory cycle by upregulation of anti-inflammatory cytokines, downregulation of proinflammatory cytokines, or both[24]. IPL significantly reduces inflammatory lesions on the skin, presumably by downregulation of tumor necrosis factor-a (TNF-a), one of the cytokines responsible for the acute phase of inflammation[54]. TNF-a and IL-1 upregulate several types of MMPs[55], and since IPL downregulates TNF-a, it means that IPL, indirectly, diminishes the levels of these MMPs. In similar ways, corticosteroids may relieve dry eye symptoms[56] by lowering the cellular levels of cytokines, chemokines, and MMPs[57].
  2. Microcirculation of the skin: IPL affects the circulation of small blood vessels[15]. The light energy is absorbed for the haemoglobin, transforming into heat. It induces localized destruction by an internal micro-thrombosis[6][24] eliminating abnormal small blood vessels around the meibomian glands and telangectasic vessels in lids and eyelid margins. This represents a reduction in the reservoir of inflammatory mediators and, consequently, eliminates a major source of inflammation from the eyelids and meibomian glands[56].

Evidence

Seo et al[58] analyzed 17 patients suffering from MGD due to facial rosacea who were treated with IPL and meibomian gland expression with a followup of 12 months. 4 Sessions were carried out at intervals of 3 weeks each, showing a significant improvement in ocular symptoms that started after 3 weeks from the first IPL session and that was maintained until the last control after 12 months. In the study, patients improved from the initial phases of treatment significantly from the third-fourth weeks after the first IPL session, with a progression to D49, coinciding with the fourth and last IPL session. It also highlights that the patients maintained the improvement until the end of the study, after almost 8 months. This means that this type of treatment has an acceptable duration, and there is no need to repeat IPL sessions frequently, which would be a major drawback, as has been pointed out by other authors’[15][16][28].

Schroeter[59] reported 60 patients with a 75 – 87% clearance of facial telangiectases with an average of 4.1 treatments. Angermeier[60] described 153 patients with a 75 – 100% clearance 2 months after treatment with 1-4 sessions. Taub[55] reported 83% redness reduction, 75% flushing reduction, improvement of skin texture, and 64% acneiform breakouts reduction with an average of 3.6 treatments IPL sessions at 3-week intervals. Mark[14] presented a reduction of blood flow by 30%, the intensity of erythema by 21%, and telangiectasia by 29% after five IPL sessions.

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