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Australasian Journal of Dermatology (2015) 56, 164–169
doi: 10.1111/ajd.12292
REVIEW ARTICLE
Ocular side–effects of topical corticosteroids: what a dermatologist needs to know Benjamin S Daniel1,2 and David Orchard1 1
Dermatology Department, Royal Children’s Hospital, Melbourne, Victoria, and 2Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
ABSTRACT Topical corticosteroids are used frequently in dermatology and atopic dermatitis without significant adverse effects. Though ocular diseases such as glaucoma and cataracts are known complications of systemic corticosteroids, the role of topical corticosteroids is limited to case reports. This review assesses the literature regarding topical steroids and their role in ocular diseases. There is evidence of harm to vision when potent topical corticosteroids are inappropriately used for prolonged periods to periorbital sites. There is no evidence to date that weak TCS to the face or potent TCS to areas other than the eyes results in ocular complications. Further research trials are required in this area. Key words: corticosteroid.
ocular
side-effect,
topical
INTRODUCTION Ocular diseases such as glaucoma and cataracts have been associated with systemic and inhaled corticosteroid use,1 but the role of topical corticosteroids (TCS) as a cause in these diseases is unknown. Concern about using TCS on the face among health professionals and some ophthalmologists2 results in the premature cessation of dermatologically prescribed TCS.3 Furthermore, the fear of potential ocular complications contributes to steroid phobia in the community as well as to poorly controlled facial atopic dermatitis. This article looks at the published literature to determine the evidence on TCS and their role in ocular diseases.
Correspondence: Dr Benjamin Daniel, Department of Dermatology, Royal Children’s Hospital, 50 Flemington Rd, Parkville, VIC, 3052, Australia. Email: [email protected] Benjamin S Daniel, MBBS. David Orchard, FACD. Conflict of interest: none Submitted 2 March 2014; accepted 4 November 2014. © 2015 The Australasian College of Dermatologists
Rates of absorption of TCS vary depending on the anatomical location and thickness of stratum corneum, with eyelid absorption 300-fold that of plantar skin.4 These rates are increased by 2–10-fold in diseased skin, such as in atopic dermatitis, due to a defective epidermal barrier. Local cutaneous side-effects such as skin atrophy and striae, telangiectasia, pigment change, allergic contact dermatitis, folliculitis, acneiform and perioral dermatitis3 may occur with the application of potent TCS to diseased or thin skin. Prolonged widespread use of TCS can lead to systemic effects with reduced adrenal gland cortisol production.5 Eye complications due to TCS are less frequently described and can include glaucoma, cataracts and infections (e.g. Herpes simplex virus). Known risk factors for cataracts and glaucoma include age, atopic dermatitis, steroids (systemic, intranasal and inhaled), and diabetes. Untreated and uncontrolled periorbital eczema itself may lead to chronic rubbing, corneal abrasion and keratoconus.6 Two main mechanisms have been proposed in the pathogenesis of TCS and ocular disease, namely via systemic absorption and secondly through seepage over the eyelid or absorption by the eyeball through the palpebral fissure.7,8 The second proposal has been more readily accepted, given the lack of other systemic side-effects associated with topical steroids.9 Glaucoma may be caused by direct contact of the TCS with the conjunctiva or through the eyelids.10 Steroid-induced lens changes, which differ from other causes of lens changes, are characterised by posterior subcapsular opacities as compared to those associated with atopic disease, being anterior.8 The posterior subcapsular cataracts may be a result of elevated plasma and aqueous glucose levels which alter cation permeability and inhibit the sodium-potassium pump of the lens.1 A literature search of PUBMED, Google and Cochrane database was conducted using the following search criteria: topical corticosteroids and ocular side-effects, glaucoma and cataracts. The references in these articles were assessed for any further case reports. In total, 14 published case reports or series and six reviews, with a total of 26 Abbreviations: IOP TCS
intraocular pressure topical corticosteroid
Ocular side-effects of TCS cases, were identified from ophthalmological, dermatological and general medicine journals. No randomised controlled tests were found during this search. Of the 26 reported cases, nine had cataracts and 21 glaucoma. Of the nine cataracts, seven were specifically reported as being posterior cataracts. Table 1 summarises the main case reports and series identified in the literature search.7–20 The main questions arising from this search include: (i) can the periorbital application of topical steroids induce glaucoma and cataracts and, if so, what quantities are required; (ii) are individuals with known ocular disease at risk of exacerbating their condition by using TCS and (iii) can topical steroids applied on other areas of the body lead to ocular complications?
Discussion of case reports and series A recent retrospective study found that the prolonged use of moderate and potent TCS periorbitally for an average of 6 months per year for almost 5 years resulted in cataracts in only 19% (7/37) of patients.6 Two of these seven cases were reported to be due to steroids, four to be age-related and one to be due to atopic dermatitis. The two cases that were thought to be due to steroids had also received oral steroids. Therefore, no cases in this series of cataract were associated with TCS alone, despite their very protracted use. Moreover, no cases of glaucoma were detected. Other case reports, however, do report an association between periorbital complications and potent TCS. Reports of ocular complications following the prolonged periorbital application of potent TCS8,13confirm what is already known among dermatologists about the association between the thickness of stratum corneum, the absorption of TCS and potential ocular complications.21 The association between weak TCS and ocular complications is less certain. Four patients developed ocular complications following the application of weak TCS to periorbital skin for a duration of 2–12 years, though three of the cases were confounded by the use of potent TCS and preceding eye pathology.4,9,11,15 Therefore, the periorbital use of a weak TCS alone has been implicated in only one case report11 and it is thought that hydrocortisone does not increase the intraocular pressures (IOP) as much as potent TCS.7,22 From these small retrospective reports, which are likely to constitute a poor source of data, there is no evidence that the periorbital application of weak TCS such as desonide or hydrocortisone results in ocular complications. Application of appropriately prescribed TCS to areas other than periorbital skin is unlikely to result in ocular disease. Potent TCS to the face for prolonged periods, however, may induce ocular disease.11 Patients typically have asymptomatic elevated IOP initially and present late with irreversible eye complications.11 In particular, in this series, Aggarwal and colleagues presented a case of refractory elevated IOP intraocular pressures with subsequent blindness in one eye following a 2-year application of 0.25% desoxymethasone cream to the face and eyelids. It is impossible to determine whether the application of TCS to the
165
eyelid or face led to this complication. This is a moderate to high potency TCS which is currently not typically prescribed in Australia. Another patient had bilateral subcapsular cataracts thought to be due to the use of TCS for 4 years. It is unknown which TCS were used in this patient. The IOP returned to normal after cessation of TCS and with the use of guttae timolol 0.5%. Another patient with periorbital atopic eczema had applied 1% hydrocortisone cream for 12 years was found to have reduced visual acuity, bilateral raised IOP and a left posterior subcapsular cataract. The IOP in the left eye was refractory to medical management and required trabeculectomy to control the pressure. Systemic complications from TCS are rare and limited to a few case reports. One case suggested cataracts, glaucoma and femoral avascular necrosis in a 30-year old man was secondary to 5 years of application of moderately potent and potent TCS for discoid eczema on the face, chest and arm.19 Bilateral osteonecrosis of the femoral head and glaucoma were reported as adverse events associated with prolonged TCS use for atopic dermatitis.17 It would therefore appear that it is possible to induce ocular complications from systemic use of TCS; however, only with prolonged use over large areas with potent TCS. There has also been some concern about the use of TCS in patients with a personal or family history of ocular disease. Patients with primary open-angle glaucoma have an increased vasoconstrictor response to corticosteroids, suggesting that they may be more prone to their effects.23 Costagliola and colleagues and Garrott and Walland describe patients with a personal or family history of ocular disease who developed raised IOP and glaucoma.12,15 Patients at high risk of ocular complications, such as those with a personal or family history of eye problems, diabetes mellitus, high myopia or those with a prolonged use of periorbital TCS may benefit from an ophthalmological evaluation, especially if visual changes occur.1,8 The education of patients and prescribing practitioners is a recurrent theme identified in these reports. Garrott and Walland 15 describe a patient who was inappropriately applying betamethasone dipropionate to his eyelids for presumed psoriasis, which was later diagnosed by a dermatologist as steroid rosacea and resolved after the cessation of TCS. This patient developed glaucoma. Sahni and colleagues report a patient with irreversible visual defects secondary to glaucoma who ignored the advice of her dermatologist by applying potent TCS (betamethasone dipropionate 0.05%) to her face and eyelids and even the telangiectasia on her eyelids, mistaking it for eczema.20 She continued to use the stronger steroid as she found it more effective and obtained an ongoing supply from her general practitioner. She was using up to 100 g every 2 weeks of the potent TCS, despite having been warned that she was using excess TCS and having been given a prescription of a weaker TCS by her dermatologist. Another patient developed glaucomatous changes requiring trabeculectomy and ongoing peripheral visual loss after using her mother’s prescribed 0.1% betamethasone cream on her eyelids daily for more than 3 years to alleviate the irritation caused by her © 2015 The Australasian College of Dermatologists
© 2015 The Australasian College of Dermatologists
Betamethasone dipropionate cream ‘Chronic’
Hydrocortisone 1% cream
Mometasone 0.1% Mentions a dermatologist who applied TCS periorbitally for atopic eczema, resulting in intractable glaucoma. On many occasions the TCS went in the eye Betamethasone butyrate propionate 0.05% ointment (chest and arms); prednisolone valerate acetate 0.3% ointment (face and neck), betamethasone dipropionate 0.05%
40 M
71 M
55 M Review
37 M
Garrott and Walland.15
Howell16
Kabata et al.17
Betamethasone (diprosone) ointment
43 M
Fat et al.14
24 years
6–9 months –
Several weeks
Daily for 3–5 Years 8 months (100 g/ week)
33 F
Daily for 7 years
2 years
Eisenlohr7
Fluocinolone acetonide ointment 0.01% Betamethasone 0.1% cream
Fluorometholone 0.25% (1 g/day)
47 M
2 years
22 M
Fluorometholone 0.25% (1 g/day)
45 M
56 M
21 F
Cubey13
Costagliola et al.
12
13 M
Various topical steroids including hydrocortisone 1% cream Clobetasone butyrate 0.05% cream; 12 years also on systemic steroids Betamethasone 0.1% cream 10 years (three times/day) Fluorometholone 0.25% (1 g/day) 2 years
25 M
2 years Intermittently for 12 years 4 years
Desoxymethasone 0.25% cream Hydrocortisone 1% cream
24 M 23 M
Age, sex Topical steroid
Duration of treatment
X-linked ichthyosis X-linked ichthyosis Facial eczema
Psoriasis
Facial eczema
Severe atopic eczema Atopic eczema
Eczema Atopic eczema
Reason for application
Face, neck, chest and arms
Atopic dermatitis
Irritation from cosmetics Sideburns, neck and – body; nil application near his eyes; (denied application near eyes) Eyelids Presumed psoriasis; later review by a dermatologist confirmed steroid rosacea Eyelids Presumed allergic dermatitis Eyelids Blepharitis – –
Eyelids
Face and eyelids
Skin
Skin
Skin
Face
Face and trunk
Periorbital skin
Face and eyelids Periorbital skin
Sites of application
Summary of published cases of topical corticosteroid (TCS) and ocular complications
Aggarwal et al.11
Table 1
√ – – –
√
– √
–
– √ √ √
√
√
√
√
√
– √
–
√
√ –
–
–
–
√ –
– √
√
√
–
– √
√ √
–
– –
–
Left posterior subcapsular
–
–
Posterior subcapsular Posterior subcapsular Posterior subcapsular –
–
– Left posterior subcapsular Bilateral subcapsular –
Location of Cataracts cataracts
Glaucoma
ocular – hypertension ocular – hypertension – √
–
–
– –
Personal or family history of eye problems
166 BS Daniel and D Orchard
29 F
Sahni et al.20
Thrice/day for 3 years Since teens (>15 years) 20 years
Fluocinolone acetonide 0.025% Methylpredniolone 0.5% Betamethasone valerate 0.12% Several times/day
Duration of treatment
Alternate difluocortolone 0.1% ointment and betamethasone 0.1% cream 5 years Beclomethasone dipropionate 0.025% on arms for 4 years; diflucortolone valerate 0.1% on face for 1 year and then changed to hydrocortisone 2.5% cream for 3 years Hydrocortisone 1%, betamethasone Since childhood 0.1%, 0.25% and 0.05% with salicylic acid. prescribed 5 times over a 2-year period; frequency of application possibly twice/ week. History obtained from GP Multiple topicals throughout Since infancy and childhood including between 16–25 betamethasone dipropionate years of age 0.05%
Prednisolone (5 mg/g) ointment (also had diabetes mellitus) Triamcinolone acetonide ointment 0.1% Betamethasone 0.1% cream
–, information not given in the source.
42 M
30 M
45 M
35 F
80 F
68 F
Ross et al.9
McLean et al.19
Michaeli-Cohen et al.8
Nielsen et al.10
Case 3
Case 2
Case 1
Age, sex Topical steroid
Continued
Katsushima et al.18 abstract only. (article in Japanese)
Table 1
– –
√
√
√ √ √ √
√
– √ √
periorbital eczema Periorbital dermatosis Atopic dermatitis
Atopic eczema
Face, periorbital, Atopic dermatitis flexures, body and limbs
Face, neck, chest and arms
Face, chest and arms Discoid eczema
√
√
–
√
–
–
–
–
√
–
√
Periorbital region Atopic dermatitis –
–
–
Unknown
Posterior subcapsular Subcapsular
–
–
–
Periorbital region Atopic dermatitis –
–
√
Location of Cataracts cataracts –
Glaucoma
√
Personal or family history of eye problems
Periorbital region Vitiligo vulgaris
Predominantly hands Atopic dermatitis and face
Face and eyelids
Bilateral periorbital
Bilateral eyelids
2 years
14 years
2 years
Sites of application
Reason for application
Ocular side-effects of TCS 167
© 2015 The Australasian College of Dermatologists
168
BS Daniel and D Orchard
Table 2 1.
2. 3. 4.
5.
Guidelines for prescribing topical corticosteroids (TCS)
Potent and very potent topical steroids have been associated with the development of serious eye disease but only if applied periorbitally for periods of months to years. In those without known eye pathology, the use of potent TCS to periorbital skin for days to weeks appears safe for the eye and does not appear to cause ocular problems. There is insufficient evidence linking the periorbital use of weak TCS with ocular complications.16 Therefore, weak TCS appear safe to use, even for prolonged periods to periorbital skin. Application of TCS to non-periorbital skin does not seem to contribute to ocular problems unless they are potent TCS and are used over large surface areas for extensive periods of time. Prolonged periorbital exposure to potent TCS and reported visual changes warrant an ophthalmology review. Patients at risk of ocular disease (e.g., those with a family or personal history of ocular disease) may be at higher risk of complications and therefore would benefit from joint treatment by a dermatologist and ophthalmologist if TCS are needed to be used around the eye for prolonged periods.16 Patients and prescribers should be educated that all TCS are not of the same potency and that their improper use can result in ocular complications; they must not apply the steroids that have been prescribed for other parts of the body to their face and periorbital regions or share TCS with others16,24
cosmetics.7 Inappropriate persistent periorbital use of potent TCS can lead to ocular complications. Incorrect diagnosis and incorrect application of potent TCS to areas with thin stratum corneum can result in both local and systemic side-effects. Table 2 identifies key points and suggestions from some major case reports.
2. 3.
4.
5.
Limitations The major limitations are the paucity of published literature about TCS used in dermatology and the role in ocular disease as well as the biased nature of small retrospective case reports.
6.
CONCLUSION
8.
Despite the widespread use of TCS in people of all ages, a lack of randomised controlled trials and cohort studies means the evidence is based only on case reports. The case reports have highlighted the need to educate health practitioners and patients in the appropriate prescription and application of TCS. Applications of potent TCS periorbitally for prolonged periods can lead to glaucoma and cataracts. Weak TCS have not been reported to contribute to ocular complications, nor has the use of potent TCS applied for days to weeks only. Patients with risk factors for ocular disease or known ocular pathology may be at increased risk and therefore extra caution should be exercised with TCS in this setting, and the consideration of ophthalmological assessment be undertaken. There is no evidence that appropriate TCS application on the face other than periorbital skin induces cataracts and glaucoma. Systemic side-effects from TCS are rare and require very large quantities of potent TCS for lengthy periods. There were no reports of ocular infections associated with TCS.
7.
9. 10.
11.
12.
13.
14. 15.
16.
17.
REFERENCES 1.
Carnahan MC, Goldstein DA. Ocular complications of topical, peri-ocular, and systemic corticosteroids. Curr. Opin. Ophthalmol. 2000; 11: 478–83.
© 2015 The Australasian College of Dermatologists
18.
McLean CJ, Lobo RF, Brazier DJ. Periocular steroid ointments may cause ocular damage. BMJ 1994; 309: 543. Callen J, Chamlin S, Eichenfield LF et al. A systematic review of the safety of topical therapies for atopic dermatitis. Br. J. Dermatol. 2007; 156: 203–21. Hengge UR, Ruzicka T, Schwartz RA et al. Adverse effects of topical glucocorticosteroids. J. Am. Acad. Dermatol. 2006; 54: 1–15; quiz 16–18. van Velsen SG, Haeck IM, Bruijnzeel-Koomen CA. Percutaneous absorption of potent topical corticosteroids in patients with severe atopic dermatitis. J. Am. Acad. Dermatol. 2010; 63: 911– 13. Haeck IM, Rouwen TJ, Timmer-de Mik L et al. Topical corticosteroids in atopic dermatitis and the risk of glaucoma and cataracts. J. Am. Acad. Dermatol. 2011; 64: 275–81. Eisenlohr JE. Glaucoma following the prolonged use of topical steroid medication to the eyelids. J. Am. Acad. Dermatol. 1983; 8: 878–81. Michaeli-Cohen A, Neudorfer M, Loewenstein A et al. Case report: visual loss caused by facial steroids. Can. Fam. Physician 1998; 44: 2462–3. Ross JJ, Jacob A, Batterbury M. Facial eczema and sightthreatening glaucoma. J. R. Soc. Med. 2004; 97: 485–6. Nielsen NV, Sorensen PN. Glaucoma induced by application of corticosteroids to the periorbital region. Arch. Dermatol. 1978; 114: 953–4. Aggarwal RK, Potamitis T, Chong NH et al. Extensive visual loss with topical facial steroids. Eye (Lond.) 1993; 7 (Pt 5): 664–6. Costagliola C, Cati-Giovannelli B, Piccirillo A et al. Cataracts associated with long-term topical steroids. Br. J. Dermatol. 1989; 120: 472–3. Cubey RB. Glaucoma following the application of corticosteroid to the skin of the eyelids. Br. J. Dermatol. 1976; 95: 207–8. Fat CL, Leslie T. Irreversible visual loss secondary to excessive topical steroid use in eczema. Br. J. Gen. Pract. 2011; 61: 583–4. Garrott HM, Walland MJ. Glaucoma from topical corticosteroids to the eyelids. Clin. Experiment. Ophthalmol. 2004; 32: 224–6. Howell JB. Eye diseases induced by topically applied steroids. The thin edge of the wedge. Arch. Dermatol. 1976; 112: 1529– 30. Kabata T, Shimanuki K, Tsuchiya H. Osteonecrosis of the femoral head and glaucoma caused by topical corticosteroid application. Mod. Rheumatol. 2011; 21: 706–9. Katsushima H. [Corticosteroid-induced glaucoma following treatment of the periorbital region]. Nihon Ganka Gakkai Zasshi 1995; 99: 238–43.
Ocular side-effects of TCS 19.
20.
21.
McLean CJ, Lobo RF, Brazier DJ. Cataracts, glaucoma, and femoral avascular necrosis caused by topical corticosteroid ointment. Lancet 1995; 345: 330. Sahni D, Darley CR, Hawk JL. Glaucoma induced by periorbital topical steroid use – a rare complication. Clin. Exp. Dermatol. 2004; 29: 617–19. Sandoval LF, Davis SA, Feldman SR. Dermatologists’ knowledge of and preferences regarding topical steroids. J. Drugs Dermatol. 2013; 12: 786–9.
22.
23.
24.
169
Cantrill HL, Palmberg PF, Zink HA et al. Comparison of in vitro potency of corticosteroids with ability to raise intraocular pressure. Am. J. Ophthalmol. 1975; 79: 1012–17. Stokes J, Walker BR, Campbell JC et al. Altered peripheral sensitivity to glucocorticoids in primary open-angle glaucoma. Invest. Ophthalmol. Vis. Sci. 2003; 44: 5163–7. Rathi SK, D’Souza P. Rational and ethical use of topical corticosteroids based on safety and efficacy. Indian J. Dermatol. 2012; 57: 251–9.
© 2015 The Australasian College of Dermatologists
Australasian Journal of Dermatology (2015) 56, 164–169
doi: 10.1111/ajd.12292
REVIEW ARTICLE
Ocular side–effects of topical corticosteroids: what a dermatologist needs to know Benjamin S Daniel1,2 and David Orchard1 1
Dermatology Department, Royal Children’s Hospital, Melbourne, Victoria, and 2Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
ABSTRACT Topical corticosteroids are used frequently in dermatology and atopic dermatitis without significant adverse effects. Though ocular diseases such as glaucoma and cataracts are known complications of systemic corticosteroids, the role of topical corticosteroids is limited to case reports. This review assesses the literature regarding topical steroids and their role in ocular diseases. There is evidence of harm to vision when potent topical corticosteroids are inappropriately used for prolonged periods to periorbital sites. There is no evidence to date that weak TCS to the face or potent TCS to areas other than the eyes results in ocular complications. Further research trials are required in this area. Key words: corticosteroid.
ocular
side-effect,
topical
INTRODUCTION Ocular diseases such as glaucoma and cataracts have been associated with systemic and inhaled corticosteroid use,1 but the role of topical corticosteroids (TCS) as a cause in these diseases is unknown. Concern about using TCS on the face among health professionals and some ophthalmologists2 results in the premature cessation of dermatologically prescribed TCS.3 Furthermore, the fear of potential ocular complications contributes to steroid phobia in the community as well as to poorly controlled facial atopic dermatitis. This article looks at the published literature to determine the evidence on TCS and their role in ocular diseases.
Correspondence: Dr Benjamin Daniel, Department of Dermatology, Royal Children’s Hospital, 50 Flemington Rd, Parkville, VIC, 3052, Australia. Email: [email protected] Benjamin S Daniel, MBBS. David Orchard, FACD. Conflict of interest: none Submitted 2 March 2014; accepted 4 November 2014. © 2015 The Australasian College of Dermatologists
Rates of absorption of TCS vary depending on the anatomical location and thickness of stratum corneum, with eyelid absorption 300-fold that of plantar skin.4 These rates are increased by 2–10-fold in diseased skin, such as in atopic dermatitis, due to a defective epidermal barrier. Local cutaneous side-effects such as skin atrophy and striae, telangiectasia, pigment change, allergic contact dermatitis, folliculitis, acneiform and perioral dermatitis3 may occur with the application of potent TCS to diseased or thin skin. Prolonged widespread use of TCS can lead to systemic effects with reduced adrenal gland cortisol production.5 Eye complications due to TCS are less frequently described and can include glaucoma, cataracts and infections (e.g. Herpes simplex virus). Known risk factors for cataracts and glaucoma include age, atopic dermatitis, steroids (systemic, intranasal and inhaled), and diabetes. Untreated and uncontrolled periorbital eczema itself may lead to chronic rubbing, corneal abrasion and keratoconus.6 Two main mechanisms have been proposed in the pathogenesis of TCS and ocular disease, namely via systemic absorption and secondly through seepage over the eyelid or absorption by the eyeball through the palpebral fissure.7,8 The second proposal has been more readily accepted, given the lack of other systemic side-effects associated with topical steroids.9 Glaucoma may be caused by direct contact of the TCS with the conjunctiva or through the eyelids.10 Steroid-induced lens changes, which differ from other causes of lens changes, are characterised by posterior subcapsular opacities as compared to those associated with atopic disease, being anterior.8 The posterior subcapsular cataracts may be a result of elevated plasma and aqueous glucose levels which alter cation permeability and inhibit the sodium-potassium pump of the lens.1 A literature search of PUBMED, Google and Cochrane database was conducted using the following search criteria: topical corticosteroids and ocular side-effects, glaucoma and cataracts. The references in these articles were assessed for any further case reports. In total, 14 published case reports or series and six reviews, with a total of 26 Abbreviations: IOP TCS
intraocular pressure topical corticosteroid
Ocular side-effects of TCS cases, were identified from ophthalmological, dermatological and general medicine journals. No randomised controlled tests were found during this search. Of the 26 reported cases, nine had cataracts and 21 glaucoma. Of the nine cataracts, seven were specifically reported as being posterior cataracts. Table 1 summarises the main case reports and series identified in the literature search.7–20 The main questions arising from this search include: (i) can the periorbital application of topical steroids induce glaucoma and cataracts and, if so, what quantities are required; (ii) are individuals with known ocular disease at risk of exacerbating their condition by using TCS and (iii) can topical steroids applied on other areas of the body lead to ocular complications?
Discussion of case reports and series A recent retrospective study found that the prolonged use of moderate and potent TCS periorbitally for an average of 6 months per year for almost 5 years resulted in cataracts in only 19% (7/37) of patients.6 Two of these seven cases were reported to be due to steroids, four to be age-related and one to be due to atopic dermatitis. The two cases that were thought to be due to steroids had also received oral steroids. Therefore, no cases in this series of cataract were associated with TCS alone, despite their very protracted use. Moreover, no cases of glaucoma were detected. Other case reports, however, do report an association between periorbital complications and potent TCS. Reports of ocular complications following the prolonged periorbital application of potent TCS8,13confirm what is already known among dermatologists about the association between the thickness of stratum corneum, the absorption of TCS and potential ocular complications.21 The association between weak TCS and ocular complications is less certain. Four patients developed ocular complications following the application of weak TCS to periorbital skin for a duration of 2–12 years, though three of the cases were confounded by the use of potent TCS and preceding eye pathology.4,9,11,15 Therefore, the periorbital use of a weak TCS alone has been implicated in only one case report11 and it is thought that hydrocortisone does not increase the intraocular pressures (IOP) as much as potent TCS.7,22 From these small retrospective reports, which are likely to constitute a poor source of data, there is no evidence that the periorbital application of weak TCS such as desonide or hydrocortisone results in ocular complications. Application of appropriately prescribed TCS to areas other than periorbital skin is unlikely to result in ocular disease. Potent TCS to the face for prolonged periods, however, may induce ocular disease.11 Patients typically have asymptomatic elevated IOP initially and present late with irreversible eye complications.11 In particular, in this series, Aggarwal and colleagues presented a case of refractory elevated IOP intraocular pressures with subsequent blindness in one eye following a 2-year application of 0.25% desoxymethasone cream to the face and eyelids. It is impossible to determine whether the application of TCS to the
165
eyelid or face led to this complication. This is a moderate to high potency TCS which is currently not typically prescribed in Australia. Another patient had bilateral subcapsular cataracts thought to be due to the use of TCS for 4 years. It is unknown which TCS were used in this patient. The IOP returned to normal after cessation of TCS and with the use of guttae timolol 0.5%. Another patient with periorbital atopic eczema had applied 1% hydrocortisone cream for 12 years was found to have reduced visual acuity, bilateral raised IOP and a left posterior subcapsular cataract. The IOP in the left eye was refractory to medical management and required trabeculectomy to control the pressure. Systemic complications from TCS are rare and limited to a few case reports. One case suggested cataracts, glaucoma and femoral avascular necrosis in a 30-year old man was secondary to 5 years of application of moderately potent and potent TCS for discoid eczema on the face, chest and arm.19 Bilateral osteonecrosis of the femoral head and glaucoma were reported as adverse events associated with prolonged TCS use for atopic dermatitis.17 It would therefore appear that it is possible to induce ocular complications from systemic use of TCS; however, only with prolonged use over large areas with potent TCS. There has also been some concern about the use of TCS in patients with a personal or family history of ocular disease. Patients with primary open-angle glaucoma have an increased vasoconstrictor response to corticosteroids, suggesting that they may be more prone to their effects.23 Costagliola and colleagues and Garrott and Walland describe patients with a personal or family history of ocular disease who developed raised IOP and glaucoma.12,15 Patients at high risk of ocular complications, such as those with a personal or family history of eye problems, diabetes mellitus, high myopia or those with a prolonged use of periorbital TCS may benefit from an ophthalmological evaluation, especially if visual changes occur.1,8 The education of patients and prescribing practitioners is a recurrent theme identified in these reports. Garrott and Walland 15 describe a patient who was inappropriately applying betamethasone dipropionate to his eyelids for presumed psoriasis, which was later diagnosed by a dermatologist as steroid rosacea and resolved after the cessation of TCS. This patient developed glaucoma. Sahni and colleagues report a patient with irreversible visual defects secondary to glaucoma who ignored the advice of her dermatologist by applying potent TCS (betamethasone dipropionate 0.05%) to her face and eyelids and even the telangiectasia on her eyelids, mistaking it for eczema.20 She continued to use the stronger steroid as she found it more effective and obtained an ongoing supply from her general practitioner. She was using up to 100 g every 2 weeks of the potent TCS, despite having been warned that she was using excess TCS and having been given a prescription of a weaker TCS by her dermatologist. Another patient developed glaucomatous changes requiring trabeculectomy and ongoing peripheral visual loss after using her mother’s prescribed 0.1% betamethasone cream on her eyelids daily for more than 3 years to alleviate the irritation caused by her © 2015 The Australasian College of Dermatologists
© 2015 The Australasian College of Dermatologists
Betamethasone dipropionate cream ‘Chronic’
Hydrocortisone 1% cream
Mometasone 0.1% Mentions a dermatologist who applied TCS periorbitally for atopic eczema, resulting in intractable glaucoma. On many occasions the TCS went in the eye Betamethasone butyrate propionate 0.05% ointment (chest and arms); prednisolone valerate acetate 0.3% ointment (face and neck), betamethasone dipropionate 0.05%
40 M
71 M
55 M Review
37 M
Garrott and Walland.15
Howell16
Kabata et al.17
Betamethasone (diprosone) ointment
43 M
Fat et al.14
24 years
6–9 months –
Several weeks
Daily for 3–5 Years 8 months (100 g/ week)
33 F
Daily for 7 years
2 years
Eisenlohr7
Fluocinolone acetonide ointment 0.01% Betamethasone 0.1% cream
Fluorometholone 0.25% (1 g/day)
47 M
2 years
22 M
Fluorometholone 0.25% (1 g/day)
45 M
56 M
21 F
Cubey13
Costagliola et al.
12
13 M
Various topical steroids including hydrocortisone 1% cream Clobetasone butyrate 0.05% cream; 12 years also on systemic steroids Betamethasone 0.1% cream 10 years (three times/day) Fluorometholone 0.25% (1 g/day) 2 years
25 M
2 years Intermittently for 12 years 4 years
Desoxymethasone 0.25% cream Hydrocortisone 1% cream
24 M 23 M
Age, sex Topical steroid
Duration of treatment
X-linked ichthyosis X-linked ichthyosis Facial eczema
Psoriasis
Facial eczema
Severe atopic eczema Atopic eczema
Eczema Atopic eczema
Reason for application
Face, neck, chest and arms
Atopic dermatitis
Irritation from cosmetics Sideburns, neck and – body; nil application near his eyes; (denied application near eyes) Eyelids Presumed psoriasis; later review by a dermatologist confirmed steroid rosacea Eyelids Presumed allergic dermatitis Eyelids Blepharitis – –
Eyelids
Face and eyelids
Skin
Skin
Skin
Face
Face and trunk
Periorbital skin
Face and eyelids Periorbital skin
Sites of application
Summary of published cases of topical corticosteroid (TCS) and ocular complications
Aggarwal et al.11
Table 1
√ – – –
√
– √
–
– √ √ √
√
√
√
√
√
– √
–
√
√ –
–
–
–
√ –
– √
√
√
–
– √
√ √
–
– –
–
Left posterior subcapsular
–
–
Posterior subcapsular Posterior subcapsular Posterior subcapsular –
–
– Left posterior subcapsular Bilateral subcapsular –
Location of Cataracts cataracts
Glaucoma
ocular – hypertension ocular – hypertension – √
–
–
– –
Personal or family history of eye problems
166 BS Daniel and D Orchard
29 F
Sahni et al.20
Thrice/day for 3 years Since teens (>15 years) 20 years
Fluocinolone acetonide 0.025% Methylpredniolone 0.5% Betamethasone valerate 0.12% Several times/day
Duration of treatment
Alternate difluocortolone 0.1% ointment and betamethasone 0.1% cream 5 years Beclomethasone dipropionate 0.025% on arms for 4 years; diflucortolone valerate 0.1% on face for 1 year and then changed to hydrocortisone 2.5% cream for 3 years Hydrocortisone 1%, betamethasone Since childhood 0.1%, 0.25% and 0.05% with salicylic acid. prescribed 5 times over a 2-year period; frequency of application possibly twice/ week. History obtained from GP Multiple topicals throughout Since infancy and childhood including between 16–25 betamethasone dipropionate years of age 0.05%
Prednisolone (5 mg/g) ointment (also had diabetes mellitus) Triamcinolone acetonide ointment 0.1% Betamethasone 0.1% cream
–, information not given in the source.
42 M
30 M
45 M
35 F
80 F
68 F
Ross et al.9
McLean et al.19
Michaeli-Cohen et al.8
Nielsen et al.10
Case 3
Case 2
Case 1
Age, sex Topical steroid
Continued
Katsushima et al.18 abstract only. (article in Japanese)
Table 1
– –
√
√
√ √ √ √
√
– √ √
periorbital eczema Periorbital dermatosis Atopic dermatitis
Atopic eczema
Face, periorbital, Atopic dermatitis flexures, body and limbs
Face, neck, chest and arms
Face, chest and arms Discoid eczema
√
√
–
√
–
–
–
–
√
–
√
Periorbital region Atopic dermatitis –
–
–
Unknown
Posterior subcapsular Subcapsular
–
–
–
Periorbital region Atopic dermatitis –
–
√
Location of Cataracts cataracts –
Glaucoma
√
Personal or family history of eye problems
Periorbital region Vitiligo vulgaris
Predominantly hands Atopic dermatitis and face
Face and eyelids
Bilateral periorbital
Bilateral eyelids
2 years
14 years
2 years
Sites of application
Reason for application
Ocular side-effects of TCS 167
© 2015 The Australasian College of Dermatologists
168
BS Daniel and D Orchard
Table 2 1.
2. 3. 4.
5.
Guidelines for prescribing topical corticosteroids (TCS)
Potent and very potent topical steroids have been associated with the development of serious eye disease but only if applied periorbitally for periods of months to years. In those without known eye pathology, the use of potent TCS to periorbital skin for days to weeks appears safe for the eye and does not appear to cause ocular problems. There is insufficient evidence linking the periorbital use of weak TCS with ocular complications.16 Therefore, weak TCS appear safe to use, even for prolonged periods to periorbital skin. Application of TCS to non-periorbital skin does not seem to contribute to ocular problems unless they are potent TCS and are used over large surface areas for extensive periods of time. Prolonged periorbital exposure to potent TCS and reported visual changes warrant an ophthalmology review. Patients at risk of ocular disease (e.g., those with a family or personal history of ocular disease) may be at higher risk of complications and therefore would benefit from joint treatment by a dermatologist and ophthalmologist if TCS are needed to be used around the eye for prolonged periods.16 Patients and prescribers should be educated that all TCS are not of the same potency and that their improper use can result in ocular complications; they must not apply the steroids that have been prescribed for other parts of the body to their face and periorbital regions or share TCS with others16,24
cosmetics.7 Inappropriate persistent periorbital use of potent TCS can lead to ocular complications. Incorrect diagnosis and incorrect application of potent TCS to areas with thin stratum corneum can result in both local and systemic side-effects. Table 2 identifies key points and suggestions from some major case reports.
2. 3.
4.
5.
Limitations The major limitations are the paucity of published literature about TCS used in dermatology and the role in ocular disease as well as the biased nature of small retrospective case reports.
6.
CONCLUSION
8.
Despite the widespread use of TCS in people of all ages, a lack of randomised controlled trials and cohort studies means the evidence is based only on case reports. The case reports have highlighted the need to educate health practitioners and patients in the appropriate prescription and application of TCS. Applications of potent TCS periorbitally for prolonged periods can lead to glaucoma and cataracts. Weak TCS have not been reported to contribute to ocular complications, nor has the use of potent TCS applied for days to weeks only. Patients with risk factors for ocular disease or known ocular pathology may be at increased risk and therefore extra caution should be exercised with TCS in this setting, and the consideration of ophthalmological assessment be undertaken. There is no evidence that appropriate TCS application on the face other than periorbital skin induces cataracts and glaucoma. Systemic side-effects from TCS are rare and require very large quantities of potent TCS for lengthy periods. There were no reports of ocular infections associated with TCS.
7.
9. 10.
11.
12.
13.
14. 15.
16.
17.
REFERENCES 1.
Carnahan MC, Goldstein DA. Ocular complications of topical, peri-ocular, and systemic corticosteroids. Curr. Opin. Ophthalmol. 2000; 11: 478–83.
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18.
McLean CJ, Lobo RF, Brazier DJ. Periocular steroid ointments may cause ocular damage. BMJ 1994; 309: 543. Callen J, Chamlin S, Eichenfield LF et al. A systematic review of the safety of topical therapies for atopic dermatitis. Br. J. Dermatol. 2007; 156: 203–21. Hengge UR, Ruzicka T, Schwartz RA et al. Adverse effects of topical glucocorticosteroids. J. Am. Acad. Dermatol. 2006; 54: 1–15; quiz 16–18. van Velsen SG, Haeck IM, Bruijnzeel-Koomen CA. Percutaneous absorption of potent topical corticosteroids in patients with severe atopic dermatitis. J. Am. Acad. Dermatol. 2010; 63: 911– 13. Haeck IM, Rouwen TJ, Timmer-de Mik L et al. Topical corticosteroids in atopic dermatitis and the risk of glaucoma and cataracts. J. Am. Acad. Dermatol. 2011; 64: 275–81. Eisenlohr JE. Glaucoma following the prolonged use of topical steroid medication to the eyelids. J. Am. Acad. Dermatol. 1983; 8: 878–81. Michaeli-Cohen A, Neudorfer M, Loewenstein A et al. Case report: visual loss caused by facial steroids. Can. Fam. Physician 1998; 44: 2462–3. Ross JJ, Jacob A, Batterbury M. Facial eczema and sightthreatening glaucoma. J. R. Soc. Med. 2004; 97: 485–6. Nielsen NV, Sorensen PN. Glaucoma induced by application of corticosteroids to the periorbital region. Arch. Dermatol. 1978; 114: 953–4. Aggarwal RK, Potamitis T, Chong NH et al. Extensive visual loss with topical facial steroids. Eye (Lond.) 1993; 7 (Pt 5): 664–6. Costagliola C, Cati-Giovannelli B, Piccirillo A et al. Cataracts associated with long-term topical steroids. Br. J. Dermatol. 1989; 120: 472–3. Cubey RB. Glaucoma following the application of corticosteroid to the skin of the eyelids. Br. J. Dermatol. 1976; 95: 207–8. Fat CL, Leslie T. Irreversible visual loss secondary to excessive topical steroid use in eczema. Br. J. Gen. Pract. 2011; 61: 583–4. Garrott HM, Walland MJ. Glaucoma from topical corticosteroids to the eyelids. Clin. Experiment. Ophthalmol. 2004; 32: 224–6. Howell JB. Eye diseases induced by topically applied steroids. The thin edge of the wedge. Arch. Dermatol. 1976; 112: 1529– 30. Kabata T, Shimanuki K, Tsuchiya H. Osteonecrosis of the femoral head and glaucoma caused by topical corticosteroid application. Mod. Rheumatol. 2011; 21: 706–9. Katsushima H. [Corticosteroid-induced glaucoma following treatment of the periorbital region]. Nihon Ganka Gakkai Zasshi 1995; 99: 238–43.
Ocular side-effects of TCS 19.
20.
21.
McLean CJ, Lobo RF, Brazier DJ. Cataracts, glaucoma, and femoral avascular necrosis caused by topical corticosteroid ointment. Lancet 1995; 345: 330. Sahni D, Darley CR, Hawk JL. Glaucoma induced by periorbital topical steroid use – a rare complication. Clin. Exp. Dermatol. 2004; 29: 617–19. Sandoval LF, Davis SA, Feldman SR. Dermatologists’ knowledge of and preferences regarding topical steroids. J. Drugs Dermatol. 2013; 12: 786–9.
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