Topical ocular drug delivery to inner ear disease and sinusitis.Abstract: Oral steroids are the main therapy for sensorineural deafness. We present the rare case of a patient whose hearing loss associated with inflammation of the inner ear and chronic sinusitis were improved with topical steroid therapy. A 68-year-old male presented with scleritis scleritis /scle·ri·tis/ (skle-ri´tis) inflammation of the sclera; it may involve the part adjoining the limbus of the cornea (anterior s.) or the underlying retina and choroid (posterior s.) . in the left eye, inflammation of the inner ear and chronic sinusitis. He received oral prednisolone prednisolone /pred·nis·o·lone/ (pred-nis´ah-lon) a synthetic glucocorticoid derived from cortisol, used in the form of the base or the acetate, sodium phosphate, or tebutate ester in replacement therapy for adrenocortical insufficiency, 10 mg/d. However, the oral prednisolone was discontinued due to severe side effects. Topical administration of 0.1% betamethasone sodium phosphate betamethasone sodium phosphate Betnesol (CA) Pharmacologic class: Glucocorticoid (inhalation) Therapeutic class: Antiasthmatic, anti-inflammatory (steroidal) Pregnancy risk category C improved the scleritis and incidentally also relieved his symptoms of recurrent otitis otitisInflammation of the ear. Otitis externa is dermatitis, usually bacterial, of the auditory canal and sometimes the external ear. It can cause a foul discharge, pain, fever, and sporadic deafness. and sinusitis sinusitis Inflammation of the sinuses. Acute sinusitis, usually due to infections such as the common cold, causes localized pain and tenderness, nasal obstruction and discharge, and malaise. after several days. Audiometry revealed recovered acoustic sensation in the right ear, from 50 dB to 20 dB, and in the left ear from 70 to 35 dB with 1,000 Hz. Topical ocular drug delivery of steroids may be effective for inner ear disease and sinusitis in patients with systemic side effects to oral steroids. Key Words: drug delivery systems, betamethasone sodium phosphate, otitis interna, sinusitis, audiometry ********** Sensorineural deafness is mainly caused by inflammation of the internal ear. The main therapy is to restrain inflammation with oral steroids. However, to our knowledge, there have been no reports concerning ocular drug delivery to inner ear disease and sinusitis. We report a rare case in which a patient with sensorineural deafness associated with inflammation of the inner ear and chronic sinusitis was improved by topical betamethasone sodium phosphate. Case Report A 68-year-old male presented with bilateral sensorineural hearing loss Sensorineural hearing loss Hearing loss caused by damage to the nerves or parts of the inner ear governing the sense of hearing. Mentioned in: Tinnitus sensorineural hearing loss and was diagnosed with chronic sinusitis with inflammation of the inner ear. Pure tone and self-recording audiometry revealed severely declined acoustic sensation in both ears (right 50 dB; left 65 dB with 1,000 Hz). The patient was treated with 10 mg/d of oral prednisolone. Nasal steroid aqueous spray was avoided because of frequent episodes of nosebleed nosebleed, nasal hemorrhage occurring as the result of local injury or disturbance. Most nosebleeds are not serious and occur when one of the small veins of the septum (the partition between the nostrils) ruptures. . The patient's deafness and sinusitis improved temporarily. However, the oral prednisolone was discontinued because of side effects of angioneurotic edema, anorexia, weight loss, and dysphoria dysphoria /dys·pho·ria/ (-for´e-ah) [Gr.] disquiet; restlessness; malaise.dysphoret´icdysphor´ic gender dysphoria within one month after treatment. The patient continued to be followed, but no steroids were given. During the observation period, he visited our affiliated hospital complaining of ocular pain and blurred vision in the left eye. The best-corrected visual acuity in the left eye was 10/20 and the intraocular pressure was 18 mm Hg. Slit-lamp examination of the left eye showed temporal ciliary ciliary /cil·i·ary/ (sil´e-e?re) pertaining to or resembling cilia; used particularly in reference to certain eye structures, as the ciliary body or muscle. cil·i·ar·y adj. 1. hyperemia hyperemia /hy·per·emia/ (-e´me-ah) engorgement; an excess of blood in a part.hypere´mic active hyperemia , arterial hyperemia that due to local or general relaxation of arterioles. due to scleritis and iritis iritis (īrī`tĭs), inflammation of the iris, the pigmented portion of the eye surrounding the pupil. The condition is sometimes associated with diabetes, with rheumatic diseases such as rheumatoid arthritis, and with infections such as (Fig. 1). The patient was treated with topical 0.1% betamethasone sodium phosphate 4 times a day for 2 weeks. With the improvement of the scleritis and iritis, the recurrent otitis and sinusitis also improved unexpectedly. Audiogram au·di·o·gram n. A graphic record of hearing ability for various sound frequencies. Audiogram A chart or graph of the results of a hearing test conducted with audiographic equipment. revealed apparent hearing recovery (right: 35 dB; left: 50 dB with 1,000 Hz). However, bilateral sensorineural hearing loss and sinusitis recurred two weeks after discontinuation of the topical ocular steroid. Pure tone and self-recording audiometry revealed declined acoustic sensation; right: 50 dB and left: 70 dB with 1,000 Hz (Fig. 2A). Readministration of topical betamethasone betamethasone /be·ta·meth·a·sone/ (ba?tah-meth´ah-son) a synthetic glucocorticoid, the most active of the antiinflammatory steroids; used topically as the benzoate, dipropionate, or valerate salts as an antiinflammatory, topically or treatment resulted in the improvement of this recurrence, although there were no ocular symptoms. Audiogram recorded right ear at 20 dB and left ear at 35 dB three months after the topical treatment (Fig. 2B). No serious systemic or local side effects such as nosebleed or ocular hypertension were observed with topical steroids. Discussion Our patient experienced scleritis and bilateral sensorineural deafness. This clinical progress may indicate the existence of an autoimmune disease like Cogan syndrome. The patient was initially treated with oral prednisolone at 10 mg/d for deafness and chronic sinusitis. In spite of a relatively low dose of steroid relative to the usual dose of 1 mg/kg/d, the patient apparently experienced side effects from the steroid. Topical steroid therapy for the scleritis unexpectedly led to improvement of the deafness and sinusitis. Topical 0.1% betamethasone sodium phosphate would calculate to 0.1 g/100 mL and an approximate volume of one eye drop is 50 [micro]L. If we further assume that the ratio between prednisolone and betamethasone is approximately 5 mg to 0.75 mg, (1) then the patient was given approximately 1.33 mg equivalents of prednisolone per day. One would think that the side effects would be the same whether the equivalent drug dose was delivered topically or systemically. However, the pharmacokinetics would be different when absorbed in the manner as follows. Ophthalmic drug delivery has been discussed in detail in many review articles. (2-6) The conjunctival con·junc·ti·val adj. Relating to the conjunctiva. conjunctival pertaining to or emanating from conjunctiva. congenital conjunctival membrane and nasal mucosa are the major systemic absorption sites for drugs delivered through the ocular route. The drug enters into the conjunctival sac and is absorbed intraocularly through the cornea cornea: see eye. and the conjunctiva. After pharmaceuticals are transferred into the eye, they are excreted to the outside of the eye. In addition, there is a pathway by which the drug enters directly into the blood through the conjunctiva. It has been recognized that the drug permeability is finer to the sclera sclera: see eye. than to the cornea. (2) On the other hand, much of the drug flows to the nasal cavity and the oral cavity through the lacrimal lacrimal /lac·ri·mal/ (lak´ri-mal) pertaining to the tears. lac·ri·mal or lach·ry·mal adj. 1. Of or relating to tears. 2. passage. Afterwards, the drug is absorbed into the nasal mucosa. The nasal mucosa is responsible for over 70% of systemic absorption of drug delivered via the ocular route in several drugs. (2) The topically applied betamethasone sodium phosphate might have exerted an effect on the paranasal sinuses and the inner ear through the lacrimal passage in this patient. The oral prednisolone caused side effects systemically in this patient. However, topical betamethasone sodium phosphate could be used long-term without side effect. Therefore, this efficient systemic absorption can be utilized as a noninvasive means of delivering the drug systemically. [FIGURE 1 OMITTED] [FIGURE 2 OMITTED] Conclusion Topical ocular drug delivery may be effective in inner ear disease and sinusitis in patients with gastritis, gastric cancer, or other systemic side effects to oral medication. References 1. Schimmer BP, Parker KL. Adrenocorticotropic hormone; adrenocortical adrenocortical /adre·no·cor·ti·cal/ (-kor´ti-k'l) pertaining to or arising from the adrenal cortex. ad·re·no·cor·ti·cal adj. Of, relating to, or derived from the adrenal cortex. steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, Gilman AG, eds. Goodman and Gilman's the Pharmacological Basis of Therapeutics, 10th ed. New York, McGraw-Hill, 2001, p 1657. 2. Lee YC, Simamora P, Pinsuwan S, et al. Review on the systemic delivery of insulin via the ocular route. Int J Pharm 2002;233:1-18. 3. Baeyens V, Gurny R. Chemical and physical parameters to tears relevant for the design of ocular drug delivery formulations. Pharm Acta Helv 1997;72:191-202. 4. Ding S. Recent development in ophthalmic drug delivery. Pharm Sci Tech Today 1998;8:328-335. 5. Lang JC. Ocular drug delivery conventional ocular formulation. Adv Drug Deliv Rev 1995;16:39-43. 6. Shell JW. Ophthalmic drug delivery systems. Surv Ophthalmol 1984;29:117-128. Even death is not to be feared by one who has lived wisely. --Hindu Prince Gautama Siddharta Tatsuya Mimura, MD, Hideharu Funatsu, MD, Tomohiko Usui, MD, Satoru Yamagami, MD, Hidetaka Noma, MD, and Shiro Amano, MD From the Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School Harvard Medical School (HMS) is one of the graduate schools of Harvard University. It is a prestigious American medical school located in the Longwood Medical Area of the Mission Hill neighborhood of Boston, Massachusetts. , Boston, MA; the Department of Ophthalmology, University of Tokyo “Todai” redirects here. For the restaurant called Todai, see Todai (restaurant). The University of Tokyo (東京大学 , Graduate School of Medicine, Tokyo, Japan; the Department of Ophthalmology, Diabetes Center Tokyo, Women's Medical University, Tokyo, Japan; and the Department of Ophthalmology, Hiroshima University, School of Medicine, Hiroshima, Japan. Reprint requests to Tatsuya Mimura, MD, PhD, The Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA, 02114. Email: mimurat-tky@umin.ac.jp Accepted April 5, 2006. RELATED ARTICLE: Key Points * Oral steroids are the main therapy for sensorineural deafness. * A topical steroid can relieve the symptoms of otitis and sinusitis through the lacrimal passage. * Ocular drugs are rarely associated with systemic side effects. * Ocular drug delivery is effective for inner ear disease and sinusitis in patients with systemic side effects to oral medications. |
|
||||||||||||||||||
Printer friendly
Cite/link
Email
Feedback
Reader Opinion