Orbital venolymphatic malformation (VLM) is present in the first decade of life as infiltrative lesions. They are composed of abnormal channels that are liable for haemorrhage and cyst formation. Periorbital haematoma is also common.¹ Periocular and orbital VLM account for 1% – 3% of the orbital masses. They are atypical vascular or lymphatic conduits with a lining of endothelial cells.² Their clinical presentation could be just a swelling, or they may present with progressive proptosis, ptosis and/or limited ocular motility. Visual loss could occur in severe cases because of sudden intralesional haemorrhage, which can lead to optic nerve compression.^2,3 The surgical excision, either total or debulking, is highly risky because of the unencapsulated, infiltrative nature of these lesions among vital orbital structures. Indications for surgery include emergency orbital decompression (e.g. severe acute haemorrhage threatening the optic nerve), refractory cases or well-circumscribed superficial lesions.⁴ Intralesional sclerotherapy with bleomycin could be an alternative to surgical excision; it could be the sole and primary modality of treatment. Bleomycin represents one of the anti-neoplastic agents that induce significant scarring and fibrosis in the case of local injection into the lesion. It is a sclerosing agent, so it helps in the regression of the lesion.³ It is indicated for lesions causing proptosis or chronic pain or pressure manifestations or lesions causing significant cosmetic disfigurement. It also can be done in deeply located lesions or intricately wrapped lesions around vital nerves and arteries where open surgery carries an unacceptable risk of blindness.⁴ Possible side effects are abnormal redness, fever, swelling, pain, hyperpigmentation and local gangrene at the injection site. Nevertheless, the efficient and safe intralesional bleomycin injection is under systematic study in relation to orbital and periorbital VLM.^3,5 The present study was conducted in order to assess the clinical and radiological responses. Also, we evaluated the number of injections, recurrence and complications associated with bleomycin sclerotherapy for the treatment of orbital and periorbital VLM.

This retrospective case series of subjects with orbital and periorbital VLM was conducted at the Sohag Ophthalmology Department, Sohag University, between April 2018 and March 2022. Detailed history was obtained regarding onset, course and duration of the lesion, the main presenting symptoms and any associated local or systemic manifestations. A full ophthalmological examination was done, including best corrected visual acuity (BCVA), spherical equivalent (SE), anterior segment examination, fundus examination and ocular motility test, followed by a detailed examination of the lesion, including its size, colour, depth and relation to surrounding structures. A computerised tomography scan (CT) and magnetic resonance imaging (MRI) of the orbit were conducted to diagnose the lesion and document its extent. Both MRI and CT scans were done before intervention and during follow-up to assess response. All data were collected for analysis.

Seventeen participants were included in this study, median 8 IQR (2.5–16.5) years, with a minimum of 9 months to a maximum of 20 years. Eight were females (47.1%, 95% CI: 26.2% – 69.0%), while nine were males (52.9%, 95% CI: 31.0% – 73.8%). They were followed for at least 36 months. The diagnosis was established clinically with the aid of CT and MRI for orbital imaging in all cases. Both BCVA and SE were matched before and after intervention with no significant difference, 0.862 and 0.72, respectively (Table 1).

Orbital and periorbital VLM are benign lymphatic tumours, featuring the growth of dilated, endothelial-lined lymphatic vessels. They can remain clinically silent or slowly become larger, leading to proptosis and limited ocular motility. Sudden enlargement because of intralesional haemorrhage can cause compressive optic neuropathy. Therefore, treatment is primarily surgical excision; however, their infiltrative nature makes complete excision critical and difficult, with risks of injury to adjacent structures. Furthermore, they are recurrent if not removed totally.^1,4,6 The injection of sclerotic agents could be a good option in the treatment of these lesions, offering improvement of symptoms and avoiding the complications of surgical intervention.^4,7 Bleomycin is one of the sclerotic agents that was first described by Shen, Gooding and Meyer in the management of orbital and periorbital VLM. The ease of procedure, either through direct injection or ultrasonically guided manoeuvre, supports its use as a primary line of management.⁸ This study showed a high success rate of intralesional bleomycin in the management of orbital and periorbital VLM with fewer operative and postoperative complications.^6,9 In the form of postoperative redness, itching and depigmentation. In our study, 15 patients showed improvement with partial or complete resolution of the lesion. Two cases only showed no improvement and required surgical intervention. According to Dave TV et al.,¹⁰ 79% of eyes with orbital VLM showed improved results with transcutaneous and/or transconjunctival non-image-guided bleomycin sclerotherapy. Similarly, Raichura et al.^5,11 revealed a highly significant response rate in 13 cases with no adverse effects or recurrence during follow-up. Lesions with macrocysts and mixed type (macro and microcysts) show better response both radiologically and clinically; the macrocystic spaces (large fluid-filled cavities) act as reservoirs. With fluid aspiration and bleomycin injection, the drug can pool and act directly inside these cavities. This provides prolonged, uniform contact with the inner lining, maximising endothelial ablation and causing complete obliteration of the lesion. Possible causes of non-response in two of our cases are the mixed nature of the lesion, as the presence of microcysts limits the distribution of the drug compared to large macrocysts, which show better response, another possible cause is the diffuse nature of the lesion, limiting complete coverage during injection. Inaccurate targeting during injection (extravasation) is an important cause to be considered in non-responding cases, especially in deep-seated lesions with optic nerve involvement or intraconal location; the drug may track into the surrounding healthy orbital fat or connective tissue rather than remaining entirely inside the malformation lumens, causing poor effect and response. In our study, we reported no recurrence. Iskandar et al. reported one case with recurrence in their study. The cause of recurrence in their case was rebleeding inside the chocolate cyst; other possible causes of recurrence may be because of hormonal triggers. Elevated hormone levels can stimulate vascular dilation or endothelial proliferation in residual, under-treated cysts.¹² No serious side effects were observed in our study. Four cases only reported itching at the site of injection, two cases reported redness, one case reported depigmentation 6 months after the third injection and no cases reported recurrence. Khusna et al. reported no serious systemic side effects, such as lung toxicity or fibrosis, in their study, which analysed the safety and efficacy of bleomycin injection for orbital and periorbital VLM.⁵ Pulmonary fibrosis is dose dependent, and fatal pulmonary fibrosis occurs when the cumulative dose exceeds 400 mg. This factor is important to be consider for patient safety and to avoid such serious side effects. Concerning safety, bleomycin intralesional injection shows a reasonable degree of safety when used to treat orbital and periorbital VLM, with minor, self-limiting side effects. No major complications were reported.¹²

Table 4 summarises the difference between our study and other published studies.^10,13,14

The difference between the radiological and clinical response to local bleomycin injection in our study and even previous studies can be attributed to the following causes. This occurs because clinical symptoms in the tight eye socket depend on fluid pressure and compliance, whereas radiological measurements depend strictly on physical volume. Bleomycin induces intense localised fibrosis (scarring). This converts a soft, stretchy, fluid-filled sponge into a hard, rigid, static block of scar tissue. As it can no longer swell or fill with blood or fluid, the clinical symptoms disappear completely, even though the static mass remains clearly visible on a post-procedure scan during radiological evaluation.

Intralesional bleomycin injection demonstrated favourable clinical and radiologic outcomes in most patients with orbital VLM in this retrospective case series. The procedure appeared relatively safe, with mainly mild local adverse effects observed during follow-up. However, larger prospective studies with standardised outcome measures are required to better establish efficacy, safety and predictors of response.