Intranasal Steroid Injections and Blindness: Our Personal Experience and a Review of the Past 60 Years

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1 The Laryngoscope VC 2014 The American Laryngological, Rhinological and Otological Society, Inc. Intranasal Steroid Injections and Blindness: Our Personal Experience and a Review of the Past 60 Years William J. Moss, MD; Kari B. Kjos, BS; Tom T. Karnezis, MD; Marc J. Lebovits, MD Objectives/Hypothesis: To assess for the safety of intranasal steroid injections. Study Design: Retrospective chart review and review of the medical literature. Methods: Seventy-eight patients with chronic rhinitis or sinusitis underwent 237 intraturbinate or intrapolyp triamcinolone acetonide injections between April 2008 and June 2013 at a single, private, outpatient otolaryngology clinic. A retrospective chart review was performed to evaluate for treatment complications, symptom improvement, and demographic data. A PubMed literature search was performed for all case series extracting the incidence of visual complications following intranasal steroid injections. All published reports of visual complications from these series and independent case reports were compiled and analyzed. Results: Of the 237 injections performed, 152 were intraturbinate and 85 were intrapolyp. One of the intrapolyp injections resulted in a transient visual change that resolved spontaneously. Nine other case series meeting the search criteria were found. Of the reported 117,669 injections performed, three resulted in visual complications yielding an estimated visual complication rate of 0.003%. All three of these events resolved spontaneously and resulted in no permanent visual deficits. A total of 19 reports of visual complications following intranasal steroid injections were discovered. Of these, the majority have insufficient detail regarding the injection technique or cite gross deviation from the correct injection protocol. Conclusion: Intranasal steroid injections are a safe treatment for chronic rhinitis and sinusitis patients. When performed correctly, there is evidence to justify the use of methylprednisolone acetate or triamcinolone acetonide injections into the inferior turbinates and nasal polyps. Key Words: Intranasal, injection, steroid, blindness. Level of Evidence: 4. Laryngoscope, 125: , 2015 INTRODUCTION First reported in 1952 by Wall and Shure, 1 intranasal steroid injections were once a routine office procedure for the treatment of allergic sinonasal disease. In 1962, Hager and Heise 2 reported on the first instance of permanent visual loss following an intraturbinate hydrocortisone injection. In the following years, a handful of similar case reports appeared, and scores of providers became wary of this technique. To this day, intranasal steroid injections are not offered by most otolaryngologists because of this exceedingly rare yet devastating complication. 3 In this article, we begin with our modest, personal experience with intranasal steroid injections and review From the Department of Otolaryngology Head and Neck Surgery, University of California, San Diego (W.J.M., K.B.K., T.T.K.); and the Department of Otolaryngology Head and Neck Surgery, VA Hospital San Diego (M.J.L.), San Diego, California, U.S.A. Editor s Note: This Manuscript was accepted for publication October 3, The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to William J. Moss, MD, University of California, San Diego, Department of Otolaryngology Head and Neck Surgery, 200 W. Arbor Dr., San Diego, CA, billy.moss85@gmail.com DOI: /lary both our technique and outcomes. We then review all other case series published on this topic within the last 60 years and compile an overall risk estimation of visual complications. We then review the instances of visual losses from these series and independent case reports and describe techniques to avoid this complication. Finally, we offer our thoughts on the acceptability of this procedure in mainstream practice. MATERIALS AND METHODS Between April 2008 and June 2013, 237 intranasal triamcinolone acetonide injections were performed on 78 patients with refractory rhinitis or sinusitis at a single, private, outpatient otolaryngology clinic. The majority of the injections were given by one of the authors (M.J.L), including the injection that led to the lone visual complication. A retrospective chart review was performed to assess the safety of these injections, symptom improvement, and demographic data. A PubMed literature search was then performed for all case series examining for the rate of visual complications following intranasal steroid injections. All series of 200 injections or more published within the past 60 years were included and analyzed. Foreign language articles and those involving injections that were not intranasal (i.e., into the skin of the external nose) were excluded. Articles that did not specifically evaluate for visual complications were excluded. An additional search for all published case reports of visual complications following

2 TABLE I. Data From Retrospective Chart Review of 237 Intranasal Triamcinolone Acetonide Injections. Demographics Average patient age: 60.4 (range 19 93) Patient gender: 48 male (62%), 23 female (38%) Indication for Injection Nasal polyps: 25 (35.2%) Allergic or nonallergic rhinitis: 44 (62%) Sinonasal discomfort: 2 (2.8%) Percentage of patients who tried inhaled steroids prior to injection: 73.2% Percentage of patients who tried oral steroids prior to injection: 32.4% Outcomes Total number of patients with follow-up: 71 (91%) Site of injection: 152 turbinate (64%), 85 polyp (36%) Percentage of patients that reported improvement from injection: 84.5% Average number of injections received by a patient: 3.4 (range 1 10) Average number of injections received by patients who reported improvement: 3.5 Safety Total complications: 2 (0.8%) Visual changes: 1 (0.4%) Palpitations/anxiety: 1 (0.4%) intranasal steroid injections was undertaken. Search terms included intranasal, intraturbinate, intrapolyp, injections, steroids, blindness, and visual complications. Technique The procedure is done with 1 cc of 40 mg/ml triamcinolone acetonide (Kenalog-40, Briggs-Myers Squibbs Co.) drawn into a 1-cc tuberculin syringe with a 21-gauge or larger bore needle. This is changed to a 1.5-inch 25-gauge, which is needed for injection into the inferior turbinates. A 25-gauge spinal needle is used to inject polyps. A mixture of three parts 4% lidocaine and one part 0.05% oxymetaxoline is sprayed onto the anterior tips of the inferior turbinates or nasal polyps. Cotton that was soaked in this same mixture is then packed into the nasal cavity. The triamcinolone acetonide syringe is shaken vigorously, the cotton is removed, and the needle is slightly bent at the hub to allow for better visualization. Using a nasal speculum and headlight for turbinate injections or a rigid endoscope for polyp injections, the needle is inserted into the anterior tip of the turbinate or nasal polyp to a depth of 1 to 2 mm. For turbinate injections, half of the syringe (0.5 cc, 20 mg) is then injected slowly and with minimal force into each turbinate, resulting in a submucosal wheal. For polyp injections, the 1.0 cc of triamcinolone is proportionally shared among the polyps. Depending upon the polyp size, it is often not possible to inject over 0.5 cc into any single polyp due to runoff. In these instances, the injection is shared among several polyps or polypoid tissue with the goal of minimizing this problem. Because chronic rhinosinusitis is rarely a unilateral problem, patients will typically undergo bilateral injections. Patients are told to return at 2- to 8-week intervals to TABLE II. Case Series Examining for the Rate of Visual Complications From Intranasal Steroid Injections. Article Steroid Formulation Site Of Injection No. Injections No. Patients Visual Complications Reported Did Visual Changes Resolve? Baker DC, Strauss, RB 15 (1962) Prednisolone tertiarybutylacetate and methylprednisolone acetate Inferior turbinate 2, n/a Becker SS et al. 6 (2007) Triamcinolone acetonide Intra-polyp 1, (diplopia) yes Dutton JM, Bumstead RM 16 (2001) Kabaker SS 17 (1975) Triamcinolone acetonide Triamcinolone acetonide and methylprednisolone acetate Intra-polyp, nasofrontal recess n/a Inferior turbinate 1,000 n/a 0 n/a Mabry RL 4 (1994) Triamcinolone acetonide Inferior turbinate 13,220 n/a 0 n/a McCleve D, Goldstein J, Silver S 18 (1978) Myers D 20 (1958) Triamcinolone acetonide Inferior turbinate 60,000 n/a 1 (decreased vision) yes Prednisolone tertiarybutylacetate, Intrapolyp n/a cortisone acetate, hydrocortisone tertiary-butylacetate, adrenocorticotropic hormone Our case series (2014) Triamcinolone acetonide Inferior turbinate and Intra-polyp Peisel FJ, Jones R, Richmond R 19 (1975) Simmons MW 21 (1960) (decreased vision) Methylprednisolone acetate Inferior turbinate 36,000 n/a 0 n/a Prednisolone tertiarybutylacetatecortisone acetate, hydrocortisone acetate Inferior turbinate and intrapolyp yes 2, n/a 797

3 TABLE III. Summary of Visual Complications From Published Series of Intranasal Steroid Injections. Total number of injections reported 117,669 Total number of visual complications 3 Rate of all visual complications 0.003% Rate of permanent visual complications 0.0% Compiled data from all referenced studies in Table II complete a series of three injections but to cancel the appointments if their symptoms resolved to their satisfaction. RESULTS Of the 237 injections performed, 152 were intraturbinate and 85 were intrapolyp. A total of 91% of patients had a follow-up visit after receiving an injection (Table I). Sixty-two percent of the injections were done for allergic or nonallergic rhinitis, 35% for nasal polyps, and 3% for sinonasal discomfort. Patients received a mean of 3.4 injections (range: 1 10) during the study time period. Eighty-four percent of patients reported clinical improvement after receiving intranasal injections. One patient reported acute anxiety and palpitations following an injection. Another patient stated that the vision decreased in his left eye during the injection of a left, ethmoid-based polyp. While symptomatic, the patient had an emergent ophthalmology consultation that was normal. His symptoms resolved spontaneously. Our PubMed query returned roughly 2,500 results; of those, the majority of them were excluded based on title and abstract content. Of the 15 manuscripts that were fully reviewed, nine retrospective studies prior to our own were ultimately included (Table II). The series total over 117,000 individual injections. These studies predominantly include intraturbinate and intrapolyp injections performed via a similar protocol to that outlined in this article. Several different steroid formulations were used, most commonly methylprednisolone acetate and triamcinolone acetonide. Of significance, Mabry 4 was noted to have several retrospective series prior to the one featured in Table II, but these were excluded because it is assumed that the data therein are included in his more recent study. A total of three visual complications were reported collectively in these series, none of which led to permanent visual deficits. In sum, this yields an estimated visual complication rate of.003%, with a rate of permanent visual complications of 0.0% among these series (Table III). In 1981, Mabry 5 published a comprehensive review of all reported cases of visual complications from intranasal steroid injections. A total of 10 cases were found, five of which had transient visual changes and five of TABLE IV. Summary of Reported Visual Complications From Intranasal Steroid Injections. Total number of visual 19 complications Total number of transient 8 visual complications Total number of permanent 11 visual complications Steroid formulation used Hydrocortisone Methylprednisolone acetate Triamcinolone acetonide Site of injection Inferior turbinate Polyp Septum Septum/ethmoid sinus Unspecified Includes data from Mabry, 5 the case series outlined in Table II, as well as separate case reports 8 13 TABLE V. Key Points of Correct Injection Technique. Key Points Done on an awake, alert patient Apply a topical vasonstrictor such as phenylephrine The steroid used should be agitated vigorously, should not be allowed to sit for an extended period of time, and should not be mixed with other agents A 25-gauge needle or smaller should be used to make a gentle, submucosal injection Safe anatomic targets include the head of the inferior turbinate and easily visible nasal polyps Rationale When awake, the patient can report visual changes and the injection can be stopped immediately. Vasoconstriction reduces bleeding and decreases the risk of intravascular injection. Steroids that are mixed with other agents or those that are allowed to sit stagnant have been shown to have increased particle formation and harbor a theoretically increased risk of complicaions. 7,22 This decreases the chance of entering and injecting into a vessel. Deep and forceful injections are not advised. These targets are the most studied and are easily performed under direct visualization. Injections into the nasal septum, directly into the sinuses, or into any postoperative field are insufficiently studied 798

4 TABLE VI. Case Reports of Intranasal Steroid Injections Resulting in Visual Complications Since Mabry 5 Case Report Case Summary Commentary Whiteman DW, Rosen DA, Pinkerton RM 8 (1980) Whiteman DW, Rosen DA, Pinkerton RM 8 (1980) Evans DE, Zahorchak ZA, Kennerdell JS 9 (1980) Garland PE, et al. 10 (1989) Johns KJ, Chandra SR 11 (1989) Wilkinson WS, et al. 12 (1989) Wolf MD 13 (2013) 34M: Following sinus surgery, methylprednisolone acetate injected into bilateral ethmoid sinuses and nasal septum, resulting in permanent, nearblindness of the right eye 23M: Following inferior turbinate reduction, methylprednisolone acetate resulting in permanent visual loss of the right eye 25F: Methylprednisolone acetate resulting in permanent visual loss of the right eye 47F: Following septoplasty, methylprednisolone acetate injected into right inferior turbinate, resulting in permanent visual loss of the right eye 37F: Methylprednisolone acetate resulting in a minor, but permanent visual loss of the left eye 22F: Triamcinolone acetonide injected into bilateral inferior turbinates, resulting in transient visual loss of the left eye 16M: Triamcinolone acetate injected into left nasal septum, resulting in permanent visual loss of the left eye Injecting into ethmoid sinuses, septum has not been studied sufficiently Minimal details regarding technique Three separate injection sites along the turbinate were used rather than a single injection into the head of the turbinate Minimal details regarding technique Essentially no details regarding technique Injection was mixed with phenylephrine, which is contraindicated Provider used notable force to make injection Done for unspecified reasons and apparently during an episode of epistaxis Injecting into the septum has sufficiently F 5 female; M 5 male. which had permanent visual losses. Mabry notes that many of these reports cite significant deviation from the correct technique or are insufficient in detail. Our PubMed search revealed an additional nine cases of visual complications from intranasal steroid injections since the time of Mabry s article. This more recent collection of cases includes two entries from the aforementioned case series (one each from our own case series, Becker et al. 6 ), as well as seven other case reports. The data compiled from Mabry s article and these subsequent reports are shown in Table IV. DISCUSSION We have estimated the risk of visual complications from an intranasal steroid injection to be an exceedingly low 0.003% based on published series. Of note, none of the three instances from these series resulted in permanent deficits. This data reflects substantial experience with both intrapolyp and intraturbinate injections using both prednisolone acetate and triamcinolone acetonide. In effect, we believe that there is sufficient evidence to justify both intraturbinate and intrapolyp injections with either of these formulations when using the correct technique. It is worth noting that, in our very modest series, we have reported one instance of a visual complication but that most other far larger case series have not. This instance was transient, and an ophthalmology examination performed while the patient was symptomatic was normal. There is certainly a possibility that, of the many thousands of injections reported in the other series, some adverse events went unnoticed or unrecorded. This highlights our study s foremost limitation: its retrospective nature. Additionally, given our use of a single database and foreign language exclusions, there remains a possibility of unevaluated case series and case reports. However, given the substantial volume of injections presented, we believe that the estimations derived from there are meaningful nonetheless. The theory behind visual losses associated with endonasal steroid injections is embolism of steroid particles into the retinal and choroidal arteries, resulting in occlusion, vasospasm, and ischemic injury This is thought to come about via retrograde flow through the ethmoidal arteries. In light of this etiology, many authors have outlined specific aspects of the steroid injection technique to avoid this devastating complication (Table V). Our review of reported instances of visual complications secondary to intranasal steroid injections has led us to a similar conclusion to that of Mabry 5 : The majority of these cases are notable for insufficient detail with regard to how the injection was performed, or they cite gross deviation from the correct technique. The cases reported since the time of Mabry s article are compiled 799

5 and critiqued in Table VI (excluding the 2 events reported from our own case series and Becker et al., 6 which are considered to have been done using correct technique). Even when performed with the correct technique, intranasal steroid injections do carry a risk of visual complications. The three instances reported in the case series at the hands of experienced providers exemplify this. The question becomes whether this is an acceptable risk. We believe that it is. For many medicationresistant chronic sinusitis patients, particularly those with nasal polyposis, the standard treatment is an endoscopic sinus surgery. Potential complications of endoscopic sinus surgery are far more diverse and include cerebrospinal fluid leak, pneumocephalus, permanent diplopia, and blindness. The overall rate of these highly morbid complications has been estimated at roughly 1% for experienced surgeons, with more minor complications occurring at a much higher rate. 14 If endoscopic sinus surgeries have been deemed to carry an acceptable risk, it would only seem appropriate that intranasal steroid injections, with a far lesser rate of serious complications, would be accepted as well. In many instances, intranasal steroid injections are done with the intent of avoiding a sinus surgery and the higher relative risk therein. CONCLUSION Correctly performed intranasal steroid injections carry a risk of visual complications of roughly.003%. There is sufficient evidence to justify both intraturbinate and intrapolyp injections using either methylprednisolone acetate or triamcinolone acetonide in appropriately selected patients. BIBLIOGRAPHY 1. Wall JW, Shure N. Intranasal cortisone: Preliminary study. Arch Otolaryngol 1952;56: Hager G, Heise G. A severe complication with permanent practical blindness of one eye following intranasal injection. HNO 1962;10: Mabry RL. Intranasal corticosteroid injection: indications, technique and complications. Otolaryngol Head Neck Surg 1979;87: Mabry RL. Intranasal steroids in rhinology: the changing role of intraturbinal injection. Ear Nose Throat J 1994;73: Mabry RL. Visual loss after intranasal corticosteroid injection: Incidence, causes and prevention. Arch Otolaryngol 1981;107: Becker SS, Rasamny JK, Han JK, Patrie J, Gross CW. Steroid injection for sinonasal polyps: the University of Virginia experience. Am J Rhinol 2007;21: Mcgrew RN, Wilson RS and Havener WH. Sudden blindness secondary to injections of common drugs in the head and neck: animal studies. Otolaryngology 1978;86: Whiteman DW, Rosen DA, Pinkerton RM. Retinal and choroidal microvascular embolism after intranasal corticosteroid injection. Am J Opthalmol 1980;89: Evans DE, Zahorchak ZA, Kennerdell JS. Visual loss as a result of primary optic nerve neuropathy after intranasal corticosteroid injection. Am J Opthalmol 1980;90: Garland PE, et al. Visual disturbance resulting from intranasal steroid injection. Case report. Arch Opthalmol 1989;107: Johns KJ, Chandra SR. Visual loss following intranasal corticosteroid injection. JAMA 1989;261: Wilkinson WS, et al. Retinal and choroidal vascular occlusion secondary to corticosteroid embolisation. Br J Opthalmol 1989;73: Wolf MD. Retinal and choroidal embolization after intranasal injection of triamcinolone acetate. Retina 2013;33: Keerl R, Stankiewicz J, Weber R, Hosemann W, Draf W. Surgical experience and complications during endonasal sinus surgery. Laryngoscope 1999;109: Baker DC, Strauss RB. Intranasal injections of long-acting corticosteroids. Ann Otol Rhinol Laryngol 1962;71: Dutton JM, Bumsted RM. Safety of steroid injections in the treatment of nasofrontal recess obstruction. Am J Rhinol 2001;15: Kabaker SS. Collected letters of the International Correspondence Society of Ophthalmologists and Otolaryngologists. Soc Ophthalmol Otolaryngol 1975;20: McCleve D, Goldstein J, Silver S. Corticosteroid injections of the nasal turbinates: Past experience and precautions. Otolaryngology 1978;86: Peisel FJ, Jones R, Richmond R. Collected letters of the International Correspondence Society of Ophthalmologists and Otolaryngologists. Soc Ophthalmol Otolaryngol 1975;20: Myers D. Experiences in the treatment of the allergic nasal polyp by the intrapolyp injection of prednisolone. Laryngoscope 1958;58: Simmons MW. Intranasal injection of corticosteroids. Calif Med 1960;92: Francis BA, Chang EL, Haik, BG. Particle size and drug interactions of injectable corticosteroids used in ophthalmic practice. Opthalmology 1996;103: