Efficacy of using peribulbar injection of amphotericin b for invasive rhino-orbital mucor-mycosis – A pilot study

**AIM:**To determine the efficacy of using Peribulbar injection of Amphotericin B for Invasive Rhino-Orbital Mucor-mycosis.

Primary Objectives:

1. To determine the role of local peribulbar injections in checking the further spread of infection in subclinical or early clinical cases of invasive Rhino-Orbital Mucor-mycosis.

Setting: Department of Ophthalmology, University College of Medical Sciences and GTB Hospital, Delhi-110095 Study Type: Prospective interventional Cohort Study. Sample Size: Intervention group shall be limited to 15 cases; as it is a pilot study

Methods: This study would be a prospective interventional cohort single-arm study which would include two types of cases:

Definition of cases:

**Type A: Sub-clinical Rhino-orbital Mucormycosis cases:**All cases being admitted at Guru Teg Bahadur Hospital, New Delhi having symptoms of Rhino-Mucormycosis with bony erosion of the (wall/walls) of orbit with orbital fat stranding or others, suggestive of breach of the orbital cavity on contrast-enhanced Computerized tomography.

Type B: Early Rhino-orbital Mucormycosis cases:  This study shall also include all cases being admitted at Guru Teg Bahadur Hospital, New Delhi having symptoms of early Rhino-orbital Mucormycosis.

The exclusion criteria:

1. Rhino-orbital Mucor mycosis patients having intraconal orbital involvement as seen on imaging.

2. Rhino-orbital Mucor mycosis patients having extraconal orbital involvement with best-corrected visual acuity less than 6/6.

Intervention:

Along with the standard of care patient shall receive extraconal/peribulbar inta-orbital local injections of Amphotericin B at the site of involvement.

The maximum number of extraconal/peribulbar local injections to be given shall be 9 (3 sets) with at least 3 days of a gap after every 3 injections.

The patients would be evaluated for improvement or worsening based on the proforma attached after 4 weeks of recruitment

The patients shall also be evaluated based on proforma attached during the course of local injections as well as for 3 days post local injections.

In case of clinico-radiological worsening, the patients would be put to the rescue therapy of****intraconal/retrobulbar Amphotericin B injections (standard of care) along with other standardof care intervention.

Outcome parameters: -

For group A: Improvement in radiological parameters and non-progression of disease into the intraconal compartment of orbit. For group B: Resolution of disease: Complete improvement in presenting ocular signs in patients having disease limited to extraconal compartment as seen on imaging.

Treatment Success: All recruited patients showing clinic-radiological improvement at the end of the 4 weeks from the first dose of peribulbar amphotericin B.

• Improvement in radiological parameters suggestive of regression of orbital disease in cases with no clinical ocular involvement.

• Complete resolution of presenting ocular signs in patients with disease limited to extraconal compartment as seen on imaging.

Treatment Failure: All recruited patients showing the following at the end of 4 weeks post first dose of peribulbar amphotericin B or at any follow-ups post recruitment.

• Clinic-radiological progression of disease into intraconal space requiring intraconal/retrobulbar injections of amphotericin B,

• Clinic-radiological worsening with involvement of intraconal space, orbital apex, optic nerve requiring exenteration.

Novelty/Innovation: As of today, there are no established guidelines or available literature for the treatment of subclinical or early orbital mucor-mycosis patients. Imaging like computerized tomography or magnetic resonance imaging of paranasal sinus and orbit can identify preclinical or subclinical disease. Early check of the infection by local therapy and combined Sino-nasal debridement may have a potential vision and functionality salvageable role. As well as prevent complications associated with retrobulbar injections( as part of the standard of care).

Previous studies/Literature: Invasive fungal rhino-orbital sinusitis (IFROS) is a highly morbid and rare disease. Available literature has demonstrated the role of functional endoscopic or conventional sinus surgery with biopsy and debridement of affected tissues when combined with intraconal injections or local amphotericin B irrigation, improves the survival as well as lowers the need for disfiguring exenteration. Limited literature and anecdotal case reports have demonstrated the role of intraconal/retrobulbar injections of amphotericin B in the management of established orbital mucor-mycosis. While few other case reports have demonstrated the role of local amphotericin B irrigation of both intraconal and/or extraconal/peribulbar spaces for local control of infection post debridement.

Extraconal/peribulbar - route as well as drug Amphotericin B is well documented in the treatment of Rhino-Orbital Mucor-mycosis in the existing literature.