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Topical timolol for an iris hemangioma
Short Reports Topical timolol for an iris hemangioma Ravali Gummi, BA,a Erin D. Stahl, MD,a,b and Justin D. Marsh, MDa,b Extraocular infantile hemangiomas have been shown to respond to oral and topical beta blockers, while there is little literature regarding the management of intraocular infantile hemangiomas with beta blockers. This case report discusses the management of an iris hemangioma with topical timolol, a treatment previously unreported in the literature.
Case Report A 4-week-old girl presented at Children’s Mercy Hospital, Kansas City, with a 2-week history of slowly increasing left iris redness, left upper eyelid swelling, and greenish-yellow discharge. On examination, a bulky, vascular lesion, measuring approximately 8 mm, was noted on the left superior palpebral conjunctiva (Figure 1A). A flat vascular lesion with tortuosity on the left iris was also noted at the 2 to 4 o’ clock position, with no elevation extending from iris margin to angle (Figure 1B). Cycloplegic refraction was 3.00 1 3.00 90 in the right eye and 4.50 1 6.50 90 in the left eye. The patient subsequently underwent examination under anesthesia. Fundus examination was normal. Ultrasound biomicroscopy (Figure 2) revealed mildly increased left iris thickness at the site of the vascular lesion, with no masses or posterior findings. Magnetic resonance imaging of the brain and orbit without contrast revealed a prominent and homogenous soft-tissue mass measuring approximately 1.8 0.5 1.8 cm in maximal transverse by craniocaudal by anteroposterior dimensions, with the mass following the contour of the globe along its superior and lateral aspects. Findings were consistent with infantile hemangioma. After a normal electrocardiogram, the child was started on topical timolol 0.5% gel for the eye and superior periocular skin. Three weeks later, the superficial left palpebral hemangioma had decreased in size, and the left iris hemangioma had completely regressed. The following month, the child demonstrated further improvement of both
Author affiliations: aUniversity of Missouri–Kansas City School of Medicine, Kansas City, Missouri; bPediatric Ophthalmology, Children’s Mercy Hospital, Kansas City, Missouri Submitted May 29, 2017. Revision accepted October 21, 2017. Correspondence: Justin D. Marsh, MD, Department of Ophthalmology, University of Missouri-Kansas City (email: [email protected]). J AAPOS 2018;-:1-3. Copyright Ó 2018, American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved. 1091-8531/$36.00 https://doi.org/10.1016/j.jaapos.2017.10.015
Journal of AAPOS
lesions, but had increased resistance to retropulsion of the left globe secondary to a growing orbital hemangioma. The patient was started on systemic propranolol for the orbital hemangioma. Following 6 months of treatment, the left iris hemangioma remained regressed (Figure 3).
Discussion Vascular anomalies of the iris represent an uncommon group of intraocular lesions. Five categories of iris vascular anomalies are recognized: iris capillary hemangioma, iris cavernous hemangioma, iris microhemangioma, iris arteriovenous malformation, and iris varix.1 All types are generally stable and regress spontaneously. Their location, however, may compromise normal visual development. Both iris capillary and cavernous hemangiomas have systemic associations; iris capillary hemangiomas have been reported in association with diffuse neonatal hemangoimas (DNH), and iris cavernous hemangiomas have been reported in association with DNH and hemangiomas elsewhere.1 Iris hemangiomas have rarely been reported in the literature. The first histologically proven case of an iris hemangioma was reported in 1929.2 Since then, many cases believed to be iris hemangiomas clinically have later been rejected on the basis of inconsistent histology.3 In 1972 Ferry questioned the existence of true vascular lesions on the anterior uveal tract,3 but in recent decades cases of histologically proven iris hemangiomas have been reported.1 Although treatment for the lesions is not well established, beta blockers are emerging as the treatment of choice for ocular hemangiomas,4-7 decreasing the need for local or systemic steroids.8 Over the past decade, beta blockers have been shown to be effective for various infantile hemangiomas, including facial and periocular hemangiomas.4,7 Although the route of administration may affect efficacy of treatment, resolution of superficial infantile hemangiomas has been reported with both oral and topical beta blockers.5-7 Numerous mechanisms have been proposed to explain why beta blockers may expedite regression of infantile hemangiomas. Vasoconstriction of vessels within hemangiomas may contribute to the immediate lightening and softening of lesions. 7 Treatment initiation with beta blocker also causes decrease in plasma vascular endothelial growth factor (VEGF), suggesting potential downregulation of VEGF.9 Finally, beta blockade seems to contribute to apoptosis of capillary endothelial cells.4,10 To our knowledge, this is the first case demonstrating effective management of an intraocular infantile hemangioma with topical beta blocker. Administration of topical timolol 0.5% led to significant regression of an iris hemangioma after 3 weeks, with no complications noted over the course of treatment. While the iris hemangioma appeared to respond well to topical treatment, signs of progression of a suspected orbital hemangioma in this patient ultimately
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FIG 2. Ultrasound biomicroscopy of left eye at presentation.
FIG 1. Clinical photographs at presentation of left superior palpebral hemangioma (A) and left iris hemangioma (B).
drove the decision to discontinue topical timolol and initiate oral propranolol. Topical timolol was an effective treatment for intraocular hemangioma in the present case. Oral beta blockers may have similar or perhaps even greater efficacy, although they may not be necessary in all cases. Comparison of the side effect profiles of oral versus topical beta blockers in children should be performed on a case-by-case basis, but it may be reasonable to consider topical timolol as a firstline treatment in the setting of iris hemangioma if the patient does not require systemic propranolol for infantile hemangiomas elsewhere.
Literature Search PubMed (MEDLINE) was searched (1900 to 2017) on February 28, 2017, using combinations of the following
FIG 3. Clinical photograph of left iris hemangioma following 6 months of treatment with beta blocker showing complete regression.
terms: hemangioma, infantile hemangioma, ocular hemangioma, and beta blocker. References 1. Broaddus E, Lystad LD, Schonfield L, Singh AD. Iris varix: report of a case and review of iris vascular anomalies. Surv Ophthalmol 2009; 54:118-27. 2. Rodin FH. Angioma of the iris: first case to be reported with histological examination. Arch Ophthalmol 1929;2:679-82. 3. Ferry AP. Hemangiomas of the iris and ciliary body: do they exist? A search for a histologically proved case. Int Ophthalmol Clin 1972;12: 177-94. 4. Painter SL, Hildebrand GD. Review of topical beta blockers as treatment for infantile hemangiomas. Surv Ophthalmol 2016;61:51-8. 5. Blatt J, Morrell DS, Buck S, Zdanski C, Gold S, Stavas J, et al. b-blockers for infantile hemangiomas: a single-institution experience. Clin Pediatr (Phila) 2011;50:757-63. 6. Haider KM, Plager DA, Neely DE, Eikenberry J, Haggstrom A. Outpatient treatment of periocular infantile hemangiomas with oral propranolol. J AAPOS 2010;14:251-6.
Journal of AAPOS
Volume - Number - / - 2018 7. Leaute-Labreze C, de la Roque ED, Hubiche T, Boralevi F, Thambo J-B, Ta€ıeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008;358:2649-51. 8. Pandey A, Gangopadhyay AN, Gopal SC, et al. Twenty years’ experience of steroids in infantile hemangioma-a developing country’s perspective. J Pediatr Surg 2009;44:688-94.
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9. Ozeki M, Nozawa A, Hori T, et al. Propranolol for infantile hemangioma: effect on plasma vascular endothelial growth factor. Pediatr Int 2016;58:1130-35. 10. Sommers Smith SK, Smith DM. Beta blockade induces apoptosis in cultured capillary endothelial cells. In Vitro Cell Dev Biol Anim 2002;38:298-304.
Case Report A 4-week-old girl presented at Children’s Mercy Hospital, Kansas City, with a 2-week history of slowly increasing left iris redness, left upper eyelid swelling, and greenish-yellow discharge. On examination, a bulky, vascular lesion, measuring approximately 8 mm, was noted on the left superior palpebral conjunctiva (Figure 1A). A flat vascular lesion with tortuosity on the left iris was also noted at the 2 to 4 o’ clock position, with no elevation extending from iris margin to angle (Figure 1B). Cycloplegic refraction was 3.00 1 3.00 90 in the right eye and 4.50 1 6.50 90 in the left eye. The patient subsequently underwent examination under anesthesia. Fundus examination was normal. Ultrasound biomicroscopy (Figure 2) revealed mildly increased left iris thickness at the site of the vascular lesion, with no masses or posterior findings. Magnetic resonance imaging of the brain and orbit without contrast revealed a prominent and homogenous soft-tissue mass measuring approximately 1.8 0.5 1.8 cm in maximal transverse by craniocaudal by anteroposterior dimensions, with the mass following the contour of the globe along its superior and lateral aspects. Findings were consistent with infantile hemangioma. After a normal electrocardiogram, the child was started on topical timolol 0.5% gel for the eye and superior periocular skin. Three weeks later, the superficial left palpebral hemangioma had decreased in size, and the left iris hemangioma had completely regressed. The following month, the child demonstrated further improvement of both
Author affiliations: aUniversity of Missouri–Kansas City School of Medicine, Kansas City, Missouri; bPediatric Ophthalmology, Children’s Mercy Hospital, Kansas City, Missouri Submitted May 29, 2017. Revision accepted October 21, 2017. Correspondence: Justin D. Marsh, MD, Department of Ophthalmology, University of Missouri-Kansas City (email: [email protected]). J AAPOS 2018;-:1-3. Copyright Ó 2018, American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved. 1091-8531/$36.00 https://doi.org/10.1016/j.jaapos.2017.10.015
Journal of AAPOS
lesions, but had increased resistance to retropulsion of the left globe secondary to a growing orbital hemangioma. The patient was started on systemic propranolol for the orbital hemangioma. Following 6 months of treatment, the left iris hemangioma remained regressed (Figure 3).
Discussion Vascular anomalies of the iris represent an uncommon group of intraocular lesions. Five categories of iris vascular anomalies are recognized: iris capillary hemangioma, iris cavernous hemangioma, iris microhemangioma, iris arteriovenous malformation, and iris varix.1 All types are generally stable and regress spontaneously. Their location, however, may compromise normal visual development. Both iris capillary and cavernous hemangiomas have systemic associations; iris capillary hemangiomas have been reported in association with diffuse neonatal hemangoimas (DNH), and iris cavernous hemangiomas have been reported in association with DNH and hemangiomas elsewhere.1 Iris hemangiomas have rarely been reported in the literature. The first histologically proven case of an iris hemangioma was reported in 1929.2 Since then, many cases believed to be iris hemangiomas clinically have later been rejected on the basis of inconsistent histology.3 In 1972 Ferry questioned the existence of true vascular lesions on the anterior uveal tract,3 but in recent decades cases of histologically proven iris hemangiomas have been reported.1 Although treatment for the lesions is not well established, beta blockers are emerging as the treatment of choice for ocular hemangiomas,4-7 decreasing the need for local or systemic steroids.8 Over the past decade, beta blockers have been shown to be effective for various infantile hemangiomas, including facial and periocular hemangiomas.4,7 Although the route of administration may affect efficacy of treatment, resolution of superficial infantile hemangiomas has been reported with both oral and topical beta blockers.5-7 Numerous mechanisms have been proposed to explain why beta blockers may expedite regression of infantile hemangiomas. Vasoconstriction of vessels within hemangiomas may contribute to the immediate lightening and softening of lesions. 7 Treatment initiation with beta blocker also causes decrease in plasma vascular endothelial growth factor (VEGF), suggesting potential downregulation of VEGF.9 Finally, beta blockade seems to contribute to apoptosis of capillary endothelial cells.4,10 To our knowledge, this is the first case demonstrating effective management of an intraocular infantile hemangioma with topical beta blocker. Administration of topical timolol 0.5% led to significant regression of an iris hemangioma after 3 weeks, with no complications noted over the course of treatment. While the iris hemangioma appeared to respond well to topical treatment, signs of progression of a suspected orbital hemangioma in this patient ultimately
1
2
Gummi, Stahl, and Marsh
Volume - Number - / - 2018
FIG 2. Ultrasound biomicroscopy of left eye at presentation.
FIG 1. Clinical photographs at presentation of left superior palpebral hemangioma (A) and left iris hemangioma (B).
drove the decision to discontinue topical timolol and initiate oral propranolol. Topical timolol was an effective treatment for intraocular hemangioma in the present case. Oral beta blockers may have similar or perhaps even greater efficacy, although they may not be necessary in all cases. Comparison of the side effect profiles of oral versus topical beta blockers in children should be performed on a case-by-case basis, but it may be reasonable to consider topical timolol as a firstline treatment in the setting of iris hemangioma if the patient does not require systemic propranolol for infantile hemangiomas elsewhere.
Literature Search PubMed (MEDLINE) was searched (1900 to 2017) on February 28, 2017, using combinations of the following
FIG 3. Clinical photograph of left iris hemangioma following 6 months of treatment with beta blocker showing complete regression.
terms: hemangioma, infantile hemangioma, ocular hemangioma, and beta blocker. References 1. Broaddus E, Lystad LD, Schonfield L, Singh AD. Iris varix: report of a case and review of iris vascular anomalies. Surv Ophthalmol 2009; 54:118-27. 2. Rodin FH. Angioma of the iris: first case to be reported with histological examination. Arch Ophthalmol 1929;2:679-82. 3. Ferry AP. Hemangiomas of the iris and ciliary body: do they exist? A search for a histologically proved case. Int Ophthalmol Clin 1972;12: 177-94. 4. Painter SL, Hildebrand GD. Review of topical beta blockers as treatment for infantile hemangiomas. Surv Ophthalmol 2016;61:51-8. 5. Blatt J, Morrell DS, Buck S, Zdanski C, Gold S, Stavas J, et al. b-blockers for infantile hemangiomas: a single-institution experience. Clin Pediatr (Phila) 2011;50:757-63. 6. Haider KM, Plager DA, Neely DE, Eikenberry J, Haggstrom A. Outpatient treatment of periocular infantile hemangiomas with oral propranolol. J AAPOS 2010;14:251-6.
Journal of AAPOS
Volume - Number - / - 2018 7. Leaute-Labreze C, de la Roque ED, Hubiche T, Boralevi F, Thambo J-B, Ta€ıeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008;358:2649-51. 8. Pandey A, Gangopadhyay AN, Gopal SC, et al. Twenty years’ experience of steroids in infantile hemangioma-a developing country’s perspective. J Pediatr Surg 2009;44:688-94.
Journal of AAPOS
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9. Ozeki M, Nozawa A, Hori T, et al. Propranolol for infantile hemangioma: effect on plasma vascular endothelial growth factor. Pediatr Int 2016;58:1130-35. 10. Sommers Smith SK, Smith DM. Beta blockade induces apoptosis in cultured capillary endothelial cells. In Vitro Cell Dev Biol Anim 2002;38:298-304.