Topical Timolol for Infantile Haemangioma of the Orbit

Abstract

Infantile haemangiomas (IHs) are the most common benign tumours of the eyelid and orbits in infancy. Beta-blockers, in the form of oral propranolol, have become first-line treatment in severe cases with functionally significant or disfiguring IH. However, adverse drug reactions of oral propranolol in infants are reported in 1 in 11 and serious or potentially life-threatening systemic side effects in 1 in 38, including dyspnoea, hypotension, hyperkalaemia, hypoglycaemia, and cyanosis, therefore requiring careful and close monitoring during the course of systemic treatment. More recently, two large meta-analyses have shown topical beta-blockers, such as timolol maleate 0.5%, to be as effective as oral propranolol in superficial IH, but with no or significantly fewer adverse effects, and have advocated that topical beta-blockers replace oral propranolol as the first-line treatment of superficial IH. We have previously reported the therapeutic response of deep periocular IH to primary topical timolol maleate 0.5% monotherapy. Here we also describe the first successful treatments of large orbital IHs with primary topical timolol maleate 0.5% monotherapy in four infants, resulting in immediate cessation of progression and rapid clinical improvement or resolution in all cases. No adverse effects and no recurrence during long-term follow-up of up to 2.5 years after cessation were seen in any of the patients treated with topical timolol maleate 0.5%.

Successful Late Treatment of Orbital Infantile Haemangiomas in Two Teenagers with Topical Transcutaneous Timolol Maleate 0.5% Alone

“…IH is the most common tumour of infancy and early childhood and the most frequent cause for eyelid and orbital tumours among infants 1 . We previously described the first successful treatments of deep periocular 21 , 22 , 23 as well as orbital IHs 24 with topical transcutaneous TM 0.5% alone as the first-line monotherapy during the acute proliferative phase in infancy. It is not known whether orbital IH with persistent proptosis may respond as well in the involutional phase if treated years later for the first time.…”

“…The treatment dose was 3 drops of TM 0.5% applied an average of 1.94 (case 1) and 2 times daily (case 2). We previously reported four infants with proptosis from orbital IH who were treated immediately on presentation in infancy during the proliferative phase with three drops of TM 0.5% two to three times daily 24 . In two infants, the time to resolution of the proptosis was only 3 months and 5.5 months, respectively.…”

“…To our best knowledge, we report here, for the first time, the successful late treatment of infantile IH with persistent proptosis with topical TM 0.5 % at 10 and 11 years after onset in two teenagers who had not received treatment in infancy. We have described the details of the transcutaneous topical application of TM 0.5 % before [24].…”

“…We have previously described the first successful and uncomplicated treatments of deep periocular IH 21 , 22 , 23 and orbital infantile IH 24 with topical timolol maleate 0.5% (TM 0.5%) during the acute proliferative phase in infancy. However, it is not known whether persistent proptosis still responds to TM 0.5% treatment in later years as well.…”

Safety Aspects of DIMS Technology Glasses, Fixation as a Marker for Amblyopia, Bielschowsky Head Tilt Test in Superior Oblique Paresis and Successful Late Topical Treatment of Orbital Infantile Hemangioma

“…In roughly 7 % of IHs, they involve the eyelid and orbit, making IH also the most common benign tumor of the orbit in infants and young children [21]. Successful pharmacological treatment of periocular and orbital hemangioma has been shown for the topical application of beta-blockers with timolol maleate 0.5 % [22] and for oral propranolol [23]. However, a previous French study of a large cohort of 906 infants with IH undergoing treatment with oral propranolol found at least one adverse drug reactions (ADR) in 8.94 % (1 : 11 infants) and a serious ADR, defined as "any ADR leading to death, life-threatening injury, hospitalisation, disability or permanent damage, or other important medical events as judged by the investigator", in 2.64% (1 :38 infants) [24].…”