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Corneal stromal damage through the eyelid after tightening using intense focused ultrasound

      Intense focused ultrasound (IFUS) tightening is a new procedure that claims to lift, tighten, and tone skin by regenerating collagen using thermal coagulation. Therefore, it is generally used for lifting the eyebrow, eyelid, lax submental (beneath the chin), and neck tissues. IFUS tightening theoretically uses ultrasound technology and bypasses the skin surface without injury to deliver energy to the deepest layers of the skin. This technique acts differently from conventional lasers that target the outer skin layers. Because of this characteristic, most dermatologists and cosmetic surgeons tend to overlook protective devices for surface organs, such as the cornea or conjunctivae. No reports to date have included ocular surface side effects after IFUS tightening. We report the first case diagnosed with a newly developed astigmatism caused by subepithelial opacity after IFUS tightening.
      A 50-year-old female visited the eye clinic with blurred vision in both eyes for 3 weeks. She had received IFUS tightening without corneal protection devices around the eyelid areas of both eyes. Her initial uncorrected right eye visual acuity was 20/40, and that of the left eye was 20/30, although her best corrected visual acuity was 20/20 in both eyes. According to her previous medical record of about 1 year ago, her uncorrected visual acuity was 20/25 without corneal opacity in both eyes. At that time, 1.0 D of corneal astigmatism at 160 degrees in the right eye and 0.75 D at 170 degrees in the left eye were observed. Subepithelial opacity was observed in both eyes on a slit-lamp examination. Subepithelial opacity was found in the superior area of the right cornea and in the inferior area of the left cornea. Corneal keratometry revealed 3.25 D of corneal astigmatism at 50 degrees in the right eye and 1.75 D at 150 degrees in the left eye. Anterior segment optical coherence tomography showed multiple round-shaped dense opaque areas in the anterior stromal depth or subepithelium (Fig. 1). Topical steroid (ocumetholone, 0.1% fluorometholone ophthalmic solution; Samil, Gyeonggi, Korea) was applied 4 times daily to resolve the corneal opacity in both eyes. One month later, her uncorrected visual acuity of both eyes was 20/25, and the corneal lesion in the right eye was nearly resolved with 2.0 D of corneal astigmatism at 50 degrees and in the left eye with 1.25 D at 150 degrees (Fig. 2).
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      Fig. 1Subepithelial opacity (arrow) is observed in the right eye (A) and the left eye (B) by slit-lamp examination. A subepithelial lesion was also observed near the anterior segment on optical coherence tomography of the right eye (C) and left eye (D). Corneal astigmatism of 3.1 D was measured in the right eye by corneal topography using a Pentacam (E). Corneal astigmatism of 1.8 D was also observed in the left eye (F).
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      Fig. 2Corneal subepithelial opacity was stationary with 2.0 D of corneal astigmatism in the right eye (A, C, E) and nearly disappeared with 1.2 D of corneal astigmatism in the left eye (B, D, F). Improved corneal flattening (arrow) in the superior area of the right cornea was observed 1 month after topical steroid application (compare E with E). The same result (arrow) was found in the inferior area of the left cornea (compare F with F).
      Ultrasound waves theoretically induce vibration in the composite molecules of a given tissue, and the friction between the molecules generates heat.
      • Alam M.
      • White L.E.
      • Martin N.
      • Witherspoon J.
      • Yoo S.
      • West D.P.
      Ultrasound tightening of facial and neck skin: a rater-blinded prospective cohort study.
      For many decades, high-intensity focused ultrasound (HIFU) has been investigated for treatment of solid tumours using thermal and cavitational injury. Based on these characteristics, IFUS, which deposits short pulses within the millisecond domain (50–200 milliseconds) and has lower power (0.5–10 J), compared with conventional HIFU, has been introduced for skin tightening and rejuvenation.
      IFUS bypasses the skin surface and delivers energy to the deepest layers of the skin. It creates well-defined thermal injury zones in the superficial musculoaponeurotic system (SMAS). Heat generated by IFUS destroys the intermolecular alpha cross-links of collagen but preserves the intramolecular beta cross-links and induces collagen shrinkage.
      • Arnoczky S.P.
      • Aksan A.
      Thermal modification of connective tissues: basic science considerations and clinical implications.
      Therefore, the thermal effect on the surface area is minimal compared with conventional ablative skin resurfacing. Negative side effects of IFUS include redness, swelling, numbness, and linear whitish wheals.
      • Suh D.H.
      • Shin M.K.
      • Lee S.J.
      • et al.
      Intense focused ultrasound tightening in Asian skin: clinical and pathologic results.
      It is generally accepted that these adverse events are temporary and do not affect the cosmetic outcome or induce significant sequelae. However, no reports have included adverse effects to the cornea, although the procedure is performed near the eyes.
      It was thought that the corneal opacity in this case was caused by inaccurate targeting with IFUS and IFUS treatment that was applied close to the delicate eyelid skin. IFUS can create a focal thermal injury to the SMAS. Eyelid skin is the thinnest skin on the human body and has little connective tissue.
      • Lee Y.
      • Hwang K.
      Skin thickness of Korean adults.
      The average thickness of eyelid skin is 521 ± 115.8 µm in the upper eyelid of Korean individuals and varies from 0.013 to 0.014 µm in white individuals. Therefore, exact targeting of IFUS is difficult, and IFUS can injure adjacent tissue. The eyeball and eyelids are very sensitive organs, so a small injury can cause distinct discomfort. Therefore, a protective device for the eyeball, including the cornea or conjunctivae, is necessary.
      We hypothesized that wound contraction results from 2 mechanisms: first, collagen shrinkage due to coagulation of collagen; and second, inflammatory shrinkage occurring due to myofibroblasts. First, collagen in the corneal stroma is mostly type I, with smaller amounts of types III, V, and VI. These collagen molecules are distinguished from other extracellular matrix components by their triple-helical conformation with alpha and beta cross-links. The thermal effect of IFUS shrinks the intermolecular alpha cross-links of collagen in the cornea, and collagen shrinkage in the cornea due to IFUS results in a density change of the cornea. That effect could induce unexpected scattering or refraction of light and create corneal astigmatism. The corneal wound healing process begins after thermal damage has occurred. Second, an inflammatory response occurs due to myofibroblasts. Corneal haze is associated with activation, migration, and differentiation of stromal keratocytes to corneal myofibroblasts. Myofibroblasts have alpha smooth muscle actin, which contracts wounds, resulting in corneal haze and astigmatism.
      The astigmatism-induced corneal opacity improved after topical steroid application in our case, as topical steroid agents inhibit collagen synthesis, enhance collagen remodeling, and reduce corneal wound contracture.
      • Nien C.J.
      • Flynn K.J.
      • Chang M.
      • Brown D
      • Jester JV.
      Reducing peak corneal haze after photorefractive keratectomy in rabbits: prednisolone acetate 1.00% versus cyclosporine A 0.05%.
      Therefore, topical steroid eye drops may relieve wound contracture due to collagen shrinkage because of collagen remodeling. Second, steroids are anti-inflammatory agents that inhibit the immune response, collagen synthesis, and neovascularization. Topical steroidal agents such as fluorometholone delay the inflammatory process and the appearance of myofibroblasts.
      • Nien C.J.
      • Flynn K.J.
      • Chang M.
      • Brown D
      • Jester JV.
      Reducing peak corneal haze after photorefractive keratectomy in rabbits: prednisolone acetate 1.00% versus cyclosporine A 0.05%.
      We prescribed topical steroid for 1 month to increase collagen remodeling and reduce the inflammatory response caused by the IFUS thermal effect. Finally, we observed a decrease in astigmatism, which was caused by corneal opacity after IFUS: 0.75 D in the right eye and 0.55 D in the left eye.
      Our case report highlights the possibility of corneal opacity developing after IFUS. Dermatologists and cosmetic surgeons should pay attention to this side effect. We recommend applying a blocking device to protect the ocular surface organs during the IFUS procedure.

      Conflicts of Interest

      This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (No. 2012R1A1A1038648).

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        • White L.E.
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        Ultrasound tightening of facial and neck skin: a rater-blinded prospective cohort study.
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        Thermal modification of connective tissues: basic science considerations and clinical implications.
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        Intense focused ultrasound tightening in Asian skin: clinical and pathologic results.
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