A fungal epidemic amidst a viral pandemic: Risk factors for development of COVID-19 associated rhino-orbital-cerebral mucormycosis in India.

PURPOSE: To study the risk factors for development of COVID-19 associated rhino-orbital-cerebral mucormycosis (ROCM) during the COVID-19 pandemic in India. METHODS: Multi-centric retrospective case-control study conducted from October 2020 to May 2021. Cases comprised of consecutive patients of COVID-19-associated ROCM (CA-ROCM) presenting at the participating ophthalmic institutes. Controls comprised of COVID-19-positive or COVID-19-recovered patients who did not develop ROCM. Comparative analysis of demographic, COVID-19 infection, treatment parameters and vaccination status between cases and controls performed. Clinical and imaging features of CA-ROCM analyzed. RESULTS: There were 179 cases and 361 controls. Mean age of presentation in cases was 52.06 years (p = .001) with male predominance (69.83%, p = .000011). Active COVID-19 infection at the time of presentation of ROCM (57.54%, p < .0001), moderate to severe COVID-19 (p < .0001), steroid administration (OR 3.63, p < .00001), uncontrolled diabetes (OR 32.83, p < .00001), random blood sugar >178 mg/dl were associated with development of CA-ROCM. Vaccination showed a protective effect (p = .0049). In cases with intracranial or cavernous sinus extension there was history of steroid administration (OR 2.89, p = .024) and orbital apex involvement on imaging (OR 6.202, p = .000037) compared to those with only rhino-orbital disease. CONCLUSION: Male gender, active COVID-19 infection, moderate or severe COVID-19, uncontrolled diabetes, steroid administration during COVID-19 treatment are risk factors for developing rhino-orbital-cerebral mucormycosis. Vaccination is protective. Random blood sugar of >178 mg/dl in COVID-19 positive or recovered patients should warrant close observation and early detection of ROCM. Presence of ophthalmoplegia, blepharoptosis at first clinical presentation and orbital apex involvement on imaging are associated with intracranial extension in ROCM.

Rhino-orbital mucormycosis following COVID-19 in previously non-diabetic, immunocompetent patients.

PURPOSE: To report a series of 13 immunocompetent patients who developed new-onset uncontrolled diabetes mellitus (DM) following COVID-19 infection and presented as rhino-orbital mucormycosis (ROM). METHOD: Retrospective study. RESULTS: A total of 127 patients of COVID-19 Associated Mucormycosis (CAM) were evaluated at four centres in India. All patients underwent endoscopic sinus debridement surgery and received systemic amphotericin-B therapy. Five patients (5/13; 38.4%) received retrobulbar amphotericin-B injections. Orbital exenteration was performed in advanced orbital involvement or progression of orbital disease in spite of maximal medical therapy. In his cohort, 13/127 (10.2%) patients presented with new onset DM, where one patient had bilateral disease. The mean age was 35.9 years (range: 20-51 years) and the mean duration from diagnosis of COVID-19 to the diagnosis of mucormycosis was 14.2 days. While 7/13 (53.8%) of the patients received systemic corticosteroids during the course of their treatment for COVID-19, six patients received no steroids or immunomodulators. The mean follow-up period was 9.2 weeks (range: 3-18 weeks) following discharge. Life salvage was possible in 100% of the cases. While overall globe salvage was possible in 42.8% (6/14 eyes), the globe could be preserved in 4/5 patients who received retrobulbar amphotericin-B injections. CONCLUSIONS: Those involved in the care of COVID-19 patients should be aware about the possibility of recent-onset DM, even in patients without a history of corticosteroid therapy. Rarely, recent-onset DM following COVID-19 may present as rhino-orbital mucormycosis, which requires aggressive surgical and medical intervention.

Clinical Presentations, Management and Outcomes of Rhino-Orbital-Cerebral Mucormycosis (ROCM) Following COVID-19: A Multi-Centric Study.

PURPOSE: To report clinical presentations and factors affecting outcomes in rhino-orbital-cerebral mucormycosis following COVID-19. METHODS: Retrospective multi-centric interventional case series of 58 eyes with rhino-orbital-cerebral mucormycosis. Demography, clinical parameters and management outcomes were noted. Factors affecting outcome and mortality were analyzed. Outcome was defined as favorable when complete resolution or stabilization without further progression of the infection was noted at last visit. RESULTS: Mean age was 55 ± 11 years (median 56). The mean HbA1c value was 10.44 ± 2.84 mg% (median 10.5). The duration between the diagnosis of COVID-19 and rhino-orbital-cerebral mucormycosis was 16 ± 21 days (median: 8 days). Thirty-six eyes (62%) had no vision at presentation. Imaging revealed paranasal sinus involvement (100%), orbital apex involvement (41%), cavernous sinus involvement (30%), and central nervous system (CNS) involvement (33%). All the patients were treated with systemic Liposomal amphotericin-B and sinus debridement. Twenty-two eyes (38%) underwent exenteration. One eye underwent transcutaneous retrobulbar amphotericin-B. The mean follow-up duration was 5.62 ± 0.78 months (median 6). Favorable outcome was seen in 35 (60%) cases. Presence of uncontrolled diabetes (p = 0.001), orbital apex involvement (p = 0.04), CNS involvement (p = 0.04), and history of steroid use (p < 0.0001) resulted in unfavorable outcome. CNS involvement was the only factor predicting mortality (p = 0.03). Mortality was seen in 20 (34%) patients. CONCLUSION: Over a third of patients with rhino-orbital-cerebral mucormycosis following COVID-19 have an unfavorable clinical outcome. Uncontrolled diabetes mellitus at presentation, involvement of the orbital apex, CNS, and the usage of steroids were associated with poorer outcomes. CNS involvement was a factor determining mortality.

An In Vitro Model Assessing the Penetration of Hyaluronidase through Optic Nerve Dura for Management of Hyaluronic Acid Facial Filler Embolism.

BACKGROUND: Blindness from ophthalmic or central retinal artery embolism is one of the most devastating complications of cosmetic filler facial injections. A proposed therapy to mitigate visual loss is prompt retrobulbar injection of hyaluronidase into the retrobulbar space. Despite Zhu et al. showing a lack of evidence and very limited published literature for reversing visual loss with this intervention, it is still widely accepted as a treatment for filler-related emboli. The purpose of this study was to evaluate the penetration of hyaluronidase through optic nerve dura using an in vitro model. METHODS: At study conclusion, five 1-cm-long segments of fresh optic nerve were obtained and injected with highly crosslinked hyaluronic acid filler, then ligated on both ends in a watertight fashion. The sections were immersed in three concentrations of hyaluronidase solution for 24 hours. Histopathologic examination of the specimen was performed to assess the presence of filler. RESULTS: The optic nerve sections were 1.1 cm (range, 0.8 to 1.2 cm). Three were immersed in 20 ml of 1500 IU/ml hyaluronidase solution and two were immersed in saline as control. After 24 hours, there was a persistence of hyaluronic acid within the optic nerves. CONCLUSIONS: There is a lack of evidence for penetration of optic nerve sheath by hyaluronidase. This raises question about the effectiveness of retrobulbar injection of hyaluronidase in reversing filler-related blindness. Further studies are needed before this can be adopted as the treatment of choice. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Invasive sino-orbital fungal infections in immunocompetent patients: a clinico-pathological study.

OBJECTIVE: Invasive sino-orbital fungal infections in immunocompetent patients are a rare clinical entity; the diagnosis and management of which is challenging. We present a large case series of invasive sino-orbital fungal granulomas in patients without pre-existing systemic immunocomprimising condition. DESIGN: Retrospective case series. PARTICIPANTS: Twenty cases of invasive sino-orbital/naso-orbital fungal granulomas in immunocompetent individuals. METHODS: We retrospectively analyzed all patients with orbital fungal granuloma who were treated at a tertiary referral eye center in South India between January 2005 and December 2012. Histopathologic confirmation of tissue invasion by fungal elements and presence of granulomatous inflammation was established in all cases included in the study. MAIN OUTCOME MEASURES: Relief of patient symptoms, resolution/no progression of disease on orbital imaging, ocular, and vision salvage were the treatment outcomes studied. RESULTS: Twenty patients (11 male and 9 female) were studied. Mean age of patients was 47.4 years ranging from 24-65 years. Aspergillus was the causative fungus in 18 cases while 2 were cases of mucormycosis. Surgical debulking of the orbital disease was performed in 7 patients. Exenteration was performed in 2 patients to prevent spread to the CNS. Medical therapy consisted of oral itraconazole in all patients and intravenous amphotericin B was administered in 2 patients. Average duration of medical therapy required to achieve relief from symptoms was 6-8 months. Recurrences are common and long-term follow-up is essential. CONCLUSIONS: Orbital fungal infections are challenging in terms of both diagnosis and treatment. Debulking along with prolonged antifungal therapy seems to be effective in controlling the infection.

Giant Perivascular Epithelioid Cell Tumor of the Orbit: A Clinicopathological Analysis and Review of the Literature.

AIM: To describe and review the clinical, radiological, and histopathological characteristics of an orbital perivascular epithelioid cell tumor (PEComa). METHODS: A systematic review of clinical records, radiological investigations, microscopic features, and immunohistochemical characteristics was done. RESULTS: A 9-year-old female child presented with a year-long history of a large orbital mass associated with painless, progressive proptosis of the right eye. Radiologically, a well-defined orbital mass was seen with no intracranial extension. Excision was performed and histopathological examination showed uniform epithelioid cells in nests separated by thin fibrovascular septae. The tumor cells stained positively for Human Melanoma Black-45, but neg-atively for desmin, S-100, smooth muscle actin, MyoD1, microphthalmia-associated transcription factor, vimentin, CD10, CD31, and CD34 with a low proliferation index of 5-7%. Based on the tumor's morphological and immuno-histochemical characteristics, a diagnosis of giant orbital PEComa was made. No recurrence was seen at the last follow-up. CONCLUSIONS: PEComas are uncommon mesenchymal neoplasms that have typical histological features, with an immunohistochemical profile of negativity for epithelial markers and positivity for melanocytic markers. For benign PEComas, complete excision is advised. However, since PEComas elsewhere in the body have been known to be malignant, a close follow-up of such cases is recommended.

Unique case of midbrain tuberculoma presenting as isolated inferior rectus palsy with nystagmus.

Isolated brain stem tuberculoma constitutes about 5% of all intracranial tuberculomas. A case of isolated inferior rectus palsy with downbeat nystagmus due to presumed midbrain tuberculoma in an immunocompetent patient is described here. This report documents a rare entity of a combination of partial third nerve palsy with pupil involvement along with downbeat nystagmus.

Primary cutaneous histoplasmosis mimicking basal cell carcinoma of the eyelid: A case report and review of literature.

We present the case of a 46 years old gentleman with longstanding ulcerative lesion of the right upper eyelid. Biopsy of the lesion revealed intracellular periodic acid-Schiff positive round to oval organisms with a surrounding clear halo suggestive of histoplasmosis. Histoplasma capsulatum specific polymerase chain reaction was positive. The patient was treated with oral antifungals and showed a prompt response to treatment. We report this rare case of primary cutaneous histoplasmosis of the eyelid in an otherwise healthy adult patient.

Eosinophilic angiocentric fibrosis of the orbit: a case report and review of literature.

Eosinophilic angiocentric fibrosis is a rare condition presenting with tumefactive lesions of the nasal cavity, paranasal sinuses, upper respiratory tract and rarely the orbit; and has characteristic histopathological features. We report the case of a 38-year-old lady with a mass lesion in right orbit. Histopathological examination of the biopsy specimen revealed extensive areas of perivascular fibrosis showing a characteristic angiocentric whirling with onion skin pattern; along with perivascular exudates of eosinophils accompanied by collection of plasma cells and lymphocytes. Rheumatology review and autoimmune screening was negative. She underwent surgical debulking followed by tapering course of oral steroids and was completely free of orbital disease at her last follow-up visit.

Crystal-storing histiocytosis masquerading ocular adnexal lymphoma: a case report and review of literature.

A case of crystal-storing histiocytosis (CSH) associated with mucosa-associated lymphoid tissue (MALT) lymphoma of orbit is reported. The patient was a 53-year-old man who presented with an 8-year history of a slowly enlarging tumor in his right orbit. Histopathologic examination revealed that the tumor was composed predominantly of sheets of spindle-shaped cells resembling striated muscle cells and scattered aggregates of atypical lymphoid cells, showing prominent plasmacytoid differentiation. Immunohistochemical analysis demonstrated that the spindle-shaped cells were CD68-positive histiocytes containing abundant crystals in their cytoplasm, consistent with the diagnosis of CSH. The aggregates of atypical lymphoid cells were diagnosed as MALT lymphoma based on their immunophenotype. Although CSH is a well-recognized manifestation in lymphoproliferative disorders, CSH complicated by MALT type of ocular adnexal lymphoma has rarely been reported. Given the rarity of this, every case presenting with such crystal-storing histiocytes warrants a thorough search for a hidden lymphoid dyscrasia.

Superior oblique muscle entrapment in orbital fracture presenting as acquired brown-like syndrome: a case report and review of literature.

Pediatric orbital trauma with fracture involving the junction of roof and medial wall leading to superior oblique entrapment is rare. Here the authors report a case of orbital fracture at the junction of roof and medial wall with entrapment of the superior oblique muscle presenting clinically as canine tooth syndrome which was surgically released. Postoperatively, the ocular motility improved, and the patient was relieved of diplopia. They recommend early surgical exploration in such cases, which lead to successful resolution of diplopia.

RPE Adenocarcinoma as the Presenting Sign of Bronchogenic Carcinoma: Diagnostic Dilemma in the Management of a Case.

Neoplasms of retinal pigment epithelium are rare and must be differentiated from choroidal melanoma. The possibility of a metastatic disease with possible primary sites as lung, breast, or kidney should be ruled out. Herein we report a case of adenocarcinoma arising from the RPE with a lung lesion suspicious of bronchogenic carcinoma. In this paper, ocular symptoms were the first sign of a systemic malignancy.

A unique case of intracorneal aberrant lenticular rest.

Phakomatous chorsitomas are rare congenital tumors of lenticular anlage believed to be caused by invagination of surface ectoderm into the mesoderm. They may present as a mass lesion in the eyelid or in the orbit. We report a rare case of lenticular anlage occurring within the corneal stroma in a 6-month-old boy.