Rhino-orbital mucormycosis has assumed pandemic proportions in post-COVID-19-infected patients. The fungus causes vascular thrombosis and hence penetration of the antifungal drugs given intravenously is inadequate. Therefore, surgical debridement needs to be done along with systemic antifungals. With the aim of avoiding exenteration and conserving the eye, retrobulbar injections of amphotericin B are given for its fungicidal properties. Using a long intravenous cannula can be effective in ensuring drug delivery into the orbit, and this obviates the need for daily injections with syringes. We used an 18-G intravenous cannula with injection port and suture holes to deliver the amphotericin into the orbit for a period of 5 days. To the best of our knowledge, this has not been reported in the literature. We did not encounter any blockage of the cannula or secondary infection in these patients. Patient comfort and compliance were satisfactory with this modality of drug delivery.
A 69-year-old male presented to the emergency department with complaints of right side upper molar pain and eye swelling for 4 days. The swelling was sudden, progressive, and extending to the cheek. He also had difficulty opening his right eye. He was a diabetic since the last 20 years on insulin and oral antidiabetic agents. He had contracted COVID-19 infection 1 month back, needed oxygen, and was administered steroids intravenously for 10 days. He underwent endoscopy by the ENT surgeon, and mucormycosis was confirmed on histopathological examination of the nasal crusts with calcofluor white and he was referred to the oculoplasty service. Examination revealed vision 6/9 in each eye with glasses. The left eye was normal. The right eyelid had diffuse edema, complete ptosis, and abduction limitation (−2) was present. There was proptosis of 3 mm. Anterior segment examination revealed pseudophakia, conjunctival chemosis, and congestion [Fig. 1a]. MRI scan revealed the presence of T2 hypointense soft tissue in the frontal and ethmoid sinuses with extension into the medial orbit suggestive of fungal invasion. While he was undergoing endoscopic sinus surgery, an 18-gauge, 13/4 inch (1.3 × 45 mm) intravenous cannula with injection port and suture holes, manufactured by B Braun Melsurgen AG, with a Vasofix Braunule Luer Lock system, was inserted superomedially in line with the inner canthus into the retrobulbar space as we would normally give a peribulbar injection and was sutured to the skin of the upper eyelid [Fig. 1c and d]. He received five injections of amphotericin B (deoxycholate form; 10 mg in 2 ml) daily. He also continued to receive intravenous liposomal amphotericin B 300 mg daily during this period; this was continued for 10 days, after which he was prescribed oral posaconazole for 2 months and advised regular follow-up. There was improvement of the ptosis and reduction of the chemosis and congestion after the injections. At the last follow-up 90 days following the injection, the patient was stable with a vision of 6/12 [Fig. 1b].
A 56-year-old lady presented with left eye loss of vision, ptosis, lid swelling, and proptosis of 5 days duration. She had been diagnosed as COVID-19 positive on RT-PCR test 11 days ago and was on supplementation oxygen 2 liters/min and had received five doses of intravenous dexamethasone. She was a known diabetic since the last 15 years and was on oral antidiabetic agents. Examination of the right eye was within normal limits. Left eye had proptosis, mild ptosis, upper and lower lid edema, and lateral rectus palsy with −4 limitation of abduction with no perception of light; fundus examination showed signs of central retinal artery occlusion [Fig. 2a]. MRI scan showed the presence of T2 hypointense soft tissue in the maxillary and ethmoid sinuses and at the intraconal and extraconal location of the left eye orbit with extension to the orbital apex [Fig. 2c and e]. After nasal endoscopy and FESS and confirmation of the diagnosis of mucormycosis, she received intravenous amphotericin B for 3 weeks followed by oral posaconazole for a period of 2 months. Injection of deoxycholate amphotericin B was given transcutaneously through the intravenous cannula in the superomedial orbit daily in the dose of 10 mg in 2 ml for 5 days. Post injection patient developed chemosis with a yellow tinge to the conjunctiva, which resolved in 10 days. At the last follow-up after 7 months, there was no ptosis or proptosis, abduction limitation was − 3 in the left eye; however, there was no light perception [Fig. 2b]. MRI scan revealed significant regression of the disease [Fig. 2d and f].
Exenteration has an adverse psychological impact and causes permanent blindness and facial disfigurement; thus, the decision to exenterate is often controversial. Moreover, post-COVID-19-infected patients have poor immunity and fragile health and may not be able to tolerate such a major surgery. Avoiding orbital exenteration may be prudent many a time as it may not be necessary or may not offer increased chances of life salvage, especially with cerebral involvement. Localized fungal infections have been successfully treated by intranasal, intrapleural, and intraarticular administration of amphotericin B. Retrobulbar injections of amphotericin B using injections and a catheter inserted during sinus surgery have been successful [Table 1].
Amphotericin B is a polyene antibiotic that binds to the cell membrane sterols, forming pores, thus causing leakage of intracellular electrolytes and derangement of metabolic activity and cell death. Amphotericin B has a large molecular weight and high protein binding and hence diffuses slowly into the tissues. The deoxycholate form has been used for retrobulbar injections with good results. We used the deoxycholate form as the orbit is an enclosed small space and risk of nephrotoxicity does not arise, in addition to the cheaper cost. Placement of an intravenous cannula can help in more diffuse drug delivery. A cannula obviates the need for daily injections, increases compliance, and is an easily accessible location. The cannula can be removed once the course of injections is complete. Blockage may occur, though unlikely, as this has a wide bore, in which case it is best to remove the cannula and insert a new one. One cannot be certain about the intraconal position of the cannula, but the needle is approximately 4.3 cm long and rests near the apex of the orbit. Multiple pockets of infection may be difficult to address with a cannula. Amphotericin B is potentially cytotoxic, incites inflammation by expression of proinflammatory cytokines, increases the edema, and may cause toxin neuropathy; this is the reason for the transient inflammation in the form of chemosis we saw after amphotericin B injection and even acute orbital compartment syndrome has been documented.
The greatest advantage of retrobulbar injection is that it is globe-sparing. Retrobulbar injections using an intravenous cannula are a valuable adjunctive modality to halt the orbital progression and provides an opportunity to avoid exenteration and save the eyeball in cases of rhino-orbital mucormycosis.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
Dr. Bharat Purandare and Dr. Parikshit Prayag, Department of Infectious diseases, Deenanath Mangeshkar Hospital, Pune and Dr. Nilanjan Bhowmick, Department of ENT, Deenanath Mangeshkar Hospital, Pune.
1. Colon-Acevedo B, Kumar J, Richard MJ, Woodward JA The role of adjunctive therapies in the management of invasive sino-orbital infection Ophthal Plast Reconstr Surg 2015 31 401 5
2. Mainville N, Jordan DR Orbital aspergillosis treated with retrobulbar amphotericin B Orbit 2012 31 15 7
3. Cahill KV, Hogan CD, Koletar SL, Gersman M Intraorbital injection of amphotericin B for palliative treatment of Aspergillus orbital abscess Ophthal Plast Reconstr Surg 1994 10 276 7
4. Wakabayashi T, Oda H, Kinoshita N, Ogasawara A, Fujishiro Y, Kawanabe W Retrobulbar amphotericin B injections for treatment of invasive sino-orbital aspergillosis Jpn J Ophthalmol 2007 51 309 11
5. Hirabayashi KE, Kalin-Hajdu E, Brodie FL, Kersten RC, Russell MS, Vagefi MR Retrobulbar injection of amphotericin B for orbital mucormycosis Ophthal Plast Reconstr Surg 2017 33 94 7
6. Hargrove RN, Wesley RE, Klippenstein KA, Fleming JC, Haik BG Indications for orbital exenteration in mucormycosis Ophthal Plast Reconstr Surg 2006 22 286 91
7. Saedi B, Sadeghi M, Seilani P Endoscopic management of rhino-cerebral mucormycosis with topical and intravenous amphotericin B J Laryngol Otol 2011 125 807 10
8. Luna JD, Ponssa XS, Rodriguez SD, Luna NC, Juárez CP Intraconal amphotericin B for the treatment of rhino-orbital mucormycosis
Ophthalmic Surg Lasers 1996 27 706 8
9. Pelton RW, Peterson EA, Patel BCK, Davis K Successful treatment of rhino-orbital mucormycosis
without exenteration Ophthal Plast Reconstr Surg 2001 17 62 6
10. Brodie FL, Kalin-Hajdu E, Kuo DS, Hirabayashi KE, Vagefi R, Kersten RC Orbital compartment syndrome following retrobulbar injection of amphotericin B for invasive fungal disease Am J Ophthalmol Case Rep 2016 1 8 10
11. Safi M, Ang MJ, Patel P, Silkiss RZ Rhino-orbital- cerebral mucormycosis (ROCM) and associated cerebritis treated with adjuvant retrobulbar amphotericin B Am J Ophthalmol Case Rep 2020 19 100771
12. Kahana A, Lucarelli MJ Use of radioopaque intraorbital catheter in the treatment of sino-orbital-cranial mucormycosis Arch Ophthalmol 2007 125 1714 5
13. Seiff SR, Choo PH, Carter SR Role of local Amphotericin B therapy for sino-orbital infections Ophthal Plast Reconstr Surg 1999 15 28 31
14. Joos ZP, Patel BC Intraorbital Irrigation of Amphotericin B in the treatment of rhino-orbital mucormycosis
Ophthal Plast Reconstr Surg 2017 33 e13 6