Intralesional bleomycin in treatment of orbital and/or adnexal venolymphatic malformations
Year: 2024
Type: article
Study design: Clinical Trial
Abstract: Orbital and/or adnexal venolymphatic malformations (OA-LMs) are benign lymphatic tumors, characterized by proliferation of anomalous dilated lymphatic vessels lined by normal endothelial cells.[1,2] Initially, they were considered as a neoplasm; now, the International Society for the Study of Vascular Anomalies (ISSVA) has classified OA-LMs as combined vascular malformations within the spectrum of arterial, venous, and lymphatic lesions that have characteristics of venous and lymphatic components and are now known as orbital and/or adnexal venolymphatic malformations.[1] It can remain silent clinically or enlarge slowly, resulting in proptosis, extraocular motility restriction, and sudden engorgement due to intralesional hemorrhage causing compressive optic neuropathy.[2] Treatment is mainly surgery, but because of the infiltrative nature, complete excision is dangerous due to risk of damage to adjacent vital structures.[3] Hence, recurrence is common in case of incomplete removal. Therefore, nonsurgical methods such as intralesional sclerosants have been used. In our study, we have assessed the efficacy of intralesional bleomycin in OA-LMs in 18 patients. A prospective interventional study was conducted over 2 years in a tertiary eye center after approval from the ethical committee. Informed written consent was taken from all. Hypersensitivity to bleomycin, deranged renal function test, pulmonary problems, pregnant/lactating women, and patients who lost to follow-up were excluded. All patients underwent detailed ophthalmological examination, and magnetic resonance imaging (MRI) of the orbit was done. Serial photographs were taken throughout. Bleomycin comes in dried powder containing 15 international units (IU). 1 IU of bleomycin is equivalent to 1 mg of bleomycin. The recommended dose is 0.25–0.5 IU/kg body weight, and the maximum cumulative dose should not exceed 5 IU/kg body weight. Bleomycin was reconstituted with normal saline and 2% lignocaine at 1:1 ratio. The volume injected into the lesion was proportional to the volume of aspirate from the lesion but did not exceed 5 ml at a session. The reconstituted solution was injected intralesionally using a 23G needle; deeper lesions were done with USG. Aspiration of the contents was sent for cytology. Injection of larger volumes can cause extravasation of the drug and compressive effects. Immediately after the procedure, pressure was applied to prevent leakage. Patients were reviewed on day 1 and 2 weeks. Repeat injections were given at intervals of 4 weeks. Injections were discontinued after a maximum of 3 or when no further sign of resolution was noticed clinically. MRI orbit was repeated 6 months after the last injection to document the radiological evidence of resolution or any recurrence. Patients were under follow-up up to 1 year after completion of the treatment course. Out of 18 patients, six were in the pediatric group (<16 years of age). All had unilateral presentation. Proptosis was the most common symptom seen in 10 patients (56%), followed by lid swelling (44%). Table 1 summarizes the demographic and clinical profiles.Table 1: Clinical summary of patientsThe number of bleomycin injections ranged from 2 to 4. Table 2 summarizes the outcome and frequency of bleomycin injections in individual patients. Figs. 1–4 show a few of the cases which we treated.Figure 1: (a) and (b) Pre-op left OA-LM; (c) and (d) Complete resolution noted post bleomycin injection given twiceFigure 2: (a) and (b) Pre-op left OA-LM with proptosis; (c) and (d) Clinically complete resolution noted post bleomycin injection given four times; (e) MRI before injection showing left OA-LM (fluid levels); (f) Imaging post injection at 6 months follow-up showing almost complete resolutionFigure 3: (a) Left eye OA-LM; (b) Reduction in swelling after two sittings of bleomycin injection; (c) Left eye complete resolution of OA-LM after four sittings of bleomycin injectionFigure 4: (a) Post maximum dose of bleomycin injection for left eye OA-LM – no resolution noted; (b) One month after surgical excision of left eye OA-LMTable 2: Outcomes of intralesional bleomycinIn our study, immediate postoperative complications were pain at the injection site, lid edema, and skin discoloration. No long-term or systemic complications were evident. Sclerosants which were widely used for orbital and extraorbital lymphatic malformations include sodium morrhuate, sodium tetradecyl sulfate, and doxycycline. The sclerosing effect of bleomycin on the vascular endothelium was first noted in the treatment of malignant pleural effusions, which led to its first use in lymphatic malformation in 1977.[3] Action of bleomycin involves apoptosis of rapidly dividing cells and inhibition of DNA synthesis with involution of the lesion by fibrosis due to induced inflammation.[3] A few systemic side effects that have been noted include fever, nausea, injection site reactions, loss of appetite, weight loss, pulmonary toxicity, and injection site skin necrosis. In our study, no such adverse reaction was seen. Pulmonary fibrosis is dose-dependent, and fatal pulmonary fibrosis occurs when the cumulative dose exceeds 400 mg.[3] Dave TV et al.[4] reported in a retrospective study that 79% of eyes with OA-LM had good outcomes with transcutaneous and/or transconjunctival non-image-guided bleomycin sclerotherapy. Gooding and Meyer stated bleomycin as an effective treatment for refractory OA-LM, showing satisfactory outcomes in four cases.[5] Raichura et al.[3] reported an excellent response in 13 patients with no adverse effects and recurrence over their follow-up period. Nuruddin et al.[6] stated 50% showed complete resolution and the other 50% had more than 70% resolution as documented radiologically and clinically. Intralesional bleomycin therapy is an effective and safe method of treatment of OA-LM without any significant ophthalmic or systemic side effects. It is a good alternative to surgical excision where it is not possible to remove the entire mass, and the patient is also concerned about cosmesis. It can also be used as an adjunct therapy to surgical debulking, where continuous negative pressure prevents chances of recurrence. Therefore, intralesional bleomycin should be considered first-line treatment of OA-LM.
Source: Indian Journal of Ophthalmology
Institution: Aravind Eye Hospital
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4404839380