Rhino-orbital infection in an immunocompromised host is a clinical emergency because infection can move rapidly from the nasal cavity and paranasal sinuses through the lamina papyracea, orbital apex, pterygopalatine fossa, cavernous sinus, and intracranial compartment. In this setting, tissue necrosis and vascular invasion can produce irreversible visual loss, cranial neuropathy, cerebral infarction, cavernous sinus thrombosis, and death within a short interval. Although bacterial orbital cellulitis remains an important differential diagnosis, the literature in severely immunocompromised adults is dominated by acute invasive fungal rhinosinusitis (AIFRS). Mucorales and Aspergillus species account for most proven cases. Mucorales characteristically show broad, irregular, sparsely septate hyphae with angioinvasion, whereas Aspergillus typically demonstrates narrower septate hyphae with acute-angle branching. Histopathology remains essential because cultures may be negative and because hyphal morphology, tissue invasion, and necrosis guide the urgency and direction of antifungal therapy. The host profile is central to disease biology. Poorly controlled diabetes and diabetic ketoacidosis promote mucormycosis through impaired phagocyte function, acidic conditions, and altered iron availability. Hematologic malignancy and profound neutropenia are particularly important in invasive aspergillosis and other molds. Solid-organ or hematopoietic stem-cell transplantation, immunosuppressive therapy, renal failure, and prolonged corticosteroid exposure further increase risk. During the COVID-19 pandemic, India and several other countries experienced an unprecedented surge of rhino-orbital-cerebral mucormycosis, highlighting the combined effect of diabetes, corticosteroids, COVID-related immune dysregulation, and health-system factors. Clinical presentation is heterogeneous. Nasal obstruction and discharge may be absent. Facial or orbital pain, periorbital edema, ptosis, proptosis, ophthalmoplegia, reduced vision, facial numbness, palatal necrosis, black nasal eschar, and cranial neuropathies should trigger immediate evaluation. In some immunosuppressed patients, fever or a subtle endoscopic mucosal change may precede extensive radiological disease. Treatment requires coordinated management by otorhinolaryngology, ophthalmology, infectious diseases, microbiology, radiology, endocrinology, critical care, and neurosurgery when needed. Current practice combines reversal of modifiable host factors, prompt systemic antifungal therapy, repeated surgical debridement of devitalized sinonasal tissue, and individualized orbital intervention. However, the role of exenteration, local amphotericin injections, azole step-down therapy, and the degree of aggressive surgery remain incompletely standardized. This systematic review aimed to synthesize four clinically relevant domains: (1) presenting symptoms, signs, and host risk factors; (2) microbiological and histopathological profiles; (3) medical and surgical treatment strategies; and (4) survival, vision, globe salvage, and neurological outcomes.

Review Design and Reporting This systematic review was structured according to the PRISMA 2020 framework. The review was not prospectively registered. Eligibility Criteria Studies were eligible when they enrolled immunocompromised or immunometabolically vulnerable patients with acute invasive sinonasal infection extending to the orbit, or provided a separable subgroup with orbital involvement. Eligible host states included diabetes mellitus, diabetic ketoacidosis, hematologic malignancy, neutropenia, solid-organ transplantation, hematopoietic stem-cell transplantation, systemic corticosteroid or other immunosuppressive exposure, renal failure, or COVID-19-associated risk. Primary cohort, case-control, cross-sectional, and case-series studies with at least 10 patients were considered. Studies had to report at least one of the following: clinical presentation, microbiological or histopathological profile, treatment, visual outcome, globe salvage, neurological extension, or mortality. Single case reports, very small case series, non-invasive fungal sinusitis, isolated orbital infection without sinonasal disease, studies without separable immunocompromised or orbital data, reviews, guidelines, editorials, and duplicate populations without additional outcomes were excluded from the primary study synthesis. Reviews and international guidelines were retained only for contextual interpretation. Information Sources and Search Strategy MEDLINE/PubMed, Embase, Scopus, Web of Science, and the Cochrane Library were searched for publications from 1 January 2000 through 30 June 2026. Reference lists of eligible studies, contemporary reviews, and clinical guidelines were also examined. A representative search combined: (rhino-orbital OR rhino-orbito-cerebral OR invasive fungal rhinosinusitis OR invasive fungal sinusitis OR mucormycosis OR aspergillosis) AND (orbit OR orbital cellulitis OR ophthalmoplegia OR visual loss) AND (immunocompromised OR diabetes OR malignancy OR neutropenia OR transplant OR corticosteroid OR COVID-19) AND (microbiology OR culture OR treatment OR amphotericin OR surgery OR outcome OR mortality). Study Selection and Data Extraction Titles and abstracts were screened, followed by full-text assessment against the prespecified eligibility criteria. Extracted variables included study design, country, sample size, immunocompromising condition, organism, sinus and orbital involvement, neurological extension, symptoms and signs, antifungal regimen, number and type of debridements, orbital procedures, visual outcome, disease progression, and mortality. Risk-of-Bias Assessment Observational cohort and comparative studies were evaluated using domains derived from ROBINS-I, with attention to case ascertainment, confounding by host severity, non-uniform microbiological testing, differences in disease stage, treatment-selection bias, missing follow-up, and outcome ascertainment. Case series were assessed using principles from the Joanna Briggs Institute case-series checklist. Overall concern was categorized as low, moderate, or high. Data Synthesis Formal pooled meta-analysis was not repeated because of substantial heterogeneity in host populations, diagnostic criteria, microbiology, disease staging, antifungal regimens, and surgical thresholds. Findings were synthesized narratively, with emphasis on consistent clinical patterns and the direction rather than the magnitude of treatment effects.

Study Selection The search framework identified 1,536 records, including 1,472 database records and 64 records identified through citation and reference-list searching. After removal of 382 duplicates, 1,154 records underwent title and abstract screening, and 1,016 were excluded. Of 138 reports sought for retrieval, six were unavailable. A total of 132 full-text reports were assessed; 119 were excluded and 13 studies were retained for qualitative synthesis. Characteristics of Included Studies The evidence base was dominated by retrospective cohorts and case series. Pre-COVID studies were enriched for hematologic malignancy, neutropenia, and diabetes, whereas COVID-era studies contained large numbers of patients with diabetes and corticosteroid exposure. Mucorales and Aspergillus were the principal pathogens. The largest dataset was the Indian COSMIC study of 2,826 patients with COVID-associated rhino-orbital-cerebral mucormycosis. Table 1. Characteristics of the principal included studies. Study Population/design Microbiology / clinical profile Treatment and principal outcome Ingley et al., 2008 USA; retrospective comparative series; 49 episodes Mucor 22; Aspergillus 27. Mucor associated with more orbital/cranial-nerve manifestations and long-term sequelae. IFS-related mortality 32% with Mucor vs 11% with Aspergillus; organism-specific differences suggested more aggressive neuro-orbital disease with Mucor. Piromchai & Thanaviratananich, 2012 Thailand; case-control; 59 invasive fungal rhinosinusitis cases Acute disease strongly associated with immunocompromise; mucosal necrosis and invasive complications characterized acute cases. Early recognition of acute invasive disease emphasized because morbidity and mortality were substantially greater than chronic invasive disease. Bakhshaee et al., 2016 Iran; 18 AIFRS cases DM 50%; leukemia 44.4%. Rhizopus oryzae 55.6%, Absidia/Mucor 16.7%, Aspergillus fumigatus 27.8%; orbital involvement 44.4%. Serial debridement plus systemic antifungal therapy; 3 deaths (16.7%). Payne et al., 2016 USA; 41 AIFRS cases over 15 years 92.7% had hematologic malignancy; ANC <500/µL and necrotic middle turbinate were highly predictive findings. Rapid biopsy-driven diagnosis and coordinated medical-surgical management were central to the institutional algorithm. Trief et al., 2016 USA; 24 invasive fungal sinus/orbit cases Orbital involvement more strongly associated with mucormycosis than Aspergillus; all patients with orbital disease and/or mucormycosis were immunosuppressed. Orbital disease carried markedly higher mortality; mucormycosis mortality exceeded Aspergillus in the cohort. Huang et al., 2021 Taiwan; 21 AIFRS cases; 9 with orbital involvement DM present in all orbital cases. Cultures included Rhizopus, Mucor/Rhizomucor, Aspergillus flavus, and Fusarium. Five of 9 orbital cases died from fungal infection; altered consciousness strongly predicted death. Sen et al., 2021 (COSMIC) India; multicenter retrospective; 2,826 COVID-associated ROCM patients DM 78%; corticosteroid exposure 87%; orbital involvement 72%. IV amphotericin B 73%; PNS debridement 56%; exenteration 15%; intraorbital amphotericin 22%; mortality 14%. Twu et al., 2021 Taiwan; 38 invasive fungal rhinosinusitis cases; 9 orbital complications Orbital complications associated with posterior ethmoid/sphenoid disease and inflammatory-marker elevation. Orbital involvement and high inflammatory burden identified patients at increased risk of poor prognosis. Patel et al., 2022 India; 458 mucormycosis patients DM 81.9%; corticosteroid exposure 79.7%; rhino-orbital disease 45.4%; cerebral extension 10.0%. IV amphotericin B 88.6%; local debridement 80.7%; reinforced early diagnosis and combined therapy. Yadav et al., 2022 India; 50 COVID-associated ROCM patients with CNS-focused analysis DM 94%; headache 86%; facial swelling 68%; EOM restriction and abnormal vision 70%; infarct 56%, cavernous sinus thrombosis 28%. High residual morbidity; vision loss/facial disfigurement common. Greater steroid exposure and inflammatory burden characterized deaths. Dallalzadeh et al., 2023 Multicenter; 46 patients/51 eyes with biopsy-proven ROCM Compared adjunctive transcutaneous retrobulbar amphotericin B (TRAMB) with no TRAMB. In localized orbital disease, exenteration was lower with TRAMB (1/8 vs 8/14); mortality did not increase. No clear benefit in extensive disease. Ebied et al., 2024 Prospective observational COVID-related AIFRS; 54 patients DM 96.3%; intraorbital and intracranial extension associated with mortality; intracranial extension independently predicted death. All received correction of risk factors, systemic antifungals, and early debridement; disease extent dominated prognosis. Karat et al., 2025 India; retrospective COVID-associated ROCM cohort; 69 patients All received IV liposomal amphotericin B and sinus debridement; orbital disease treated with TRAMB and selective globe/orbit surgery. Cumulative mortality 27%; severe COVID-19, DKA, CNS involvement, and increasing age predicted mortality; globe preservation was frequent. Host Factors and Clinical Presentation Diabetes mellitus emerged as the dominant host factor in rhino-orbital mucormycosis. In the COSMIC cohort, 78% of patients had diabetes, and corticosteroid exposure was documented in 87%. Patel et al. similarly reported diabetes in more than four-fifths of patients. In contrast, hematologic malignancy and profound neutropenia were prominent in pre-COVID AIFRS series, particularly those enriched for invasive aspergillosis. Pain and neuro-ophthalmic dysfunction were important red flags. Orbital or facial pain, eyelid edema, ptosis, proptosis, ophthalmoplegia, decreased visual acuity, facial hypoesthesia, and headache were recurrent presentations. Nasal symptoms were often absent or nonspecific. Huang et al. found decreased visual acuity in 88.9% and extraocular-movement limitation in 77.8% of orbital-involved AIFRS cases. Altered consciousness was particularly ominous: all five infection-related deaths in that orbital subgroup presented with conscious disturbance. Black eschar or palatal necrosis was specific when present but was not sufficiently sensitive to exclude early disease. Neutropenic patients may present with fever and subtle endoscopic mucosal discoloration rather than extensive pain or inflammation. Consequently, the threshold for nasal endoscopy and biopsy must remain low in severely immunosuppressed hosts. Anatomical Pattern and Imaging The ethmoid and maxillary sinuses were the most frequently involved sites, with posterior ethmoid and sphenoid disease particularly relevant to orbital-apical and intracranial spread. CT is useful for bony anatomy, sinus opacification, extrasinus fat infiltration, and operative planning, whereas contrast-enhanced MRI is more sensitive for orbital apex, cavernous sinus, vascular, perineural, and intracranial involvement. Orbital fat stranding, extraocular-muscle enlargement, subperiosteal collections, non-enhancing devitalized tissue, optic-nerve involvement, cavernous sinus thrombosis, internal carotid involvement, infarction, and cerebral abscess indicate progressively advanced disease. In COVID-era ROCM, higher stage consistently correlated with progression and mortality. Microbiological Profiles The microbiological spectrum was dominated by Mucorales and Aspergillus. Rhizopus was the most frequently reported Mucorales genus in several cohorts. Mucor and Rhizomucor were also described, and older series reported Absidia (now Lichtheimia-related taxonomy). Aspergillus fumigatus and Aspergillus flavus were frequent among hematologic-malignancy and neutropenic populations. Fusarium was uncommon but clinically important because susceptibility patterns and breakthrough infection under mold-active prophylaxis can complicate management. Comparative studies suggest biologically meaningful organism-specific patterns. Ingley et al. reported more orbital and cranial nerve sequelae in Mucor than Aspergillus disease. Trief et al. similarly found mucormycosis to be disproportionately represented among patients with orbital involvement, with higher mortality than aspergillosis in that cohort. These findings support immediate tissue diagnosis rather than empiric assumption that all invasive rhino-orbital infections are mucormycosis. Bacterial co-infection was variably reported. When present, organisms reflected healthcare exposure, necrotic tissue, and secondary infection, and antibiotic therapy was generally susceptibility-directed. The available literature did not permit a reliable pathogen-specific synthesis of bacterial rhino-orbital infection independent of invasive fungal disease. Microbiological and Histopathological Pattern Table 2. Dominant microbiological and histopathological patterns in rhino-orbital infection. Pathogen group Typical host association Histopathological clue Clinical implication Mucorales (especially Rhizopus) Uncontrolled diabetes/DKA; corticosteroids; COVID-associated immune-metabolic risk; transplant Broad, irregular, sparsely septate or nonseptate hyphae; frequent angioinvasion and necrosis Rapid orbital-apical/vascular extension; liposomal amphotericin B and urgent debridement Aspergillus spp. Hematologic malignancy, neutropenia, transplant; also diabetes Narrow septate hyphae with acute-angle branching; angioinvasion Voriconazole usually preferred; surgery for invasive sinonasal source control Fusarium and other molds Profound immunosuppression; occasionally breakthrough disease on prophylaxis Septate hyphae; species identification may require culture/molecular methods Susceptibility can be unpredictable; infectious-disease/mycology input essential Bacterial co-infection Necrotic tissue, prolonged hospitalization, invasive devices Suppurative inflammation and positive bacterial culture Treat according to culture and susceptibility; does not replace mold-active therapy when invasive fungal disease is proven Treatment Strategies Systemic Antifungal Therapy For proven or strongly suspected mucormycosis, high-dose liposomal amphotericin B remains the principal first-line drug in international guidance. Renal function, potassium, magnesium, and infusion-related toxicity require close monitoring. Posaconazole or isavuconazole may be used as step-down therapy, salvage therapy, or alternatives when amphotericin B cannot be continued. For invasive aspergillosis, voriconazole remains the conventional first-line agent, with isavuconazole an accepted alternative in appropriate clinical settings. Antifungal therapy should be modified once tissue morphology, culture, species identification, susceptibility data, and organ function are available. Sinonasal Debridement Early endoscopic sinonasal debridement was the most consistent surgical intervention across studies. Debridement serves both diagnostic and therapeutic purposes: obtaining viable-edge tissue for histopathology and culture, reducing necrotic burden, improving local oxygenation and drug penetration, and allowing serial endoscopic assessment. Repeated procedures are often necessary because visible disease may progress despite apparently complete initial removal. Orbital Surgery and Exenteration The role of orbital exenteration has shifted from reflexive radical surgery toward stage- and response-based decision-making. In limited orbital disease without extensive apex, cavernous sinus, or cerebral extension, orbit-preserving strategies are increasingly attempted. In the COSMIC cohort, exenteration was not associated with improved outcomes in early orbital stages but appeared more useful in advanced disease. Interpretation is limited by strong confounding by disease severity and treatment selection. Retrobulbar Amphotericin B Local amphotericin B injection has emerged as an adjunct intended to increase orbital drug exposure and avoid exenteration. In the multicenter Dallalzadeh study, patients with localized orbital involvement receiving transcutaneous retrobulbar amphotericin B had fewer exenterations without an observed mortality penalty. This apparent benefit did not extend clearly to extensive apical, cavernous sinus, bilateral, or intracranial disease. Evidence remains observational, and injection technique, dose, frequency, and patient-selection thresholds vary. Reversal of Host Factors Correction of the underlying immunometabolic state is a core component of treatment. This includes rapid glycemic control and treatment of ketoacidosis, reduction of unnecessary corticosteroids or immunosuppression when clinically feasible, recovery from neutropenia, and optimization of renal function. Failure to reverse host factors can undermine otherwise adequate antifungal and surgical therapy. Treatment Outcomes and Prognostic Factors Mortality varied widely according to population and disease stage. Earlier mixed AIFRS cohorts frequently reported mortality exceeding 30%, particularly with orbital or intracranial involvement. Selected contemporary cohorts achieved lower mortality through earlier imaging, endoscopy, liposomal amphotericin B, and aggressive endoscopic source control. The large COSMIC study reported 14% mortality at final follow-up, although follow-up duration and missing outcome data varied. In contrast, small cohorts enriched for intracranial disease showed substantially greater death and disability. Vision was often lost even among survivors. Central retinal artery or ophthalmic artery occlusion, optic-nerve ischemia, orbital apex involvement, and extensive angioinvasion can cause irreversible visual loss before systemic control is achieved. Therefore, survival, globe salvage, and useful vision should be considered distinct outcomes. Across studies, the most consistent poor prognostic factors were altered consciousness, cavernous sinus or intracranial extension, advanced radiological stage, diabetic ketoacidosis, severe systemic illness, delayed diagnosis, and persistent immunosuppression. Organism type also mattered: Mucorales infection tended to produce more orbital and cranial-nerve morbidity than Aspergillus in comparative cohorts. Summary of Clinically Actionable Findings Table 3. Summary of clinically actionable findings. Domain Consistent finding Clinical implication Host factors Diabetes/DKA dominate mucormycosis; hematologic malignancy/neutropenia dominate many aspergillosis series; corticosteroid exposure was highly prevalent in COVID-associated ROCM. Treat host reversal as part of source control, not as a separate secondary task. Red flags Orbital pain, visual loss, ophthalmoplegia, ptosis, proptosis, facial numbness, necrosis, altered consciousness. Urgent nasal endoscopy/biopsy and contrast imaging are warranted; normal-looking anterior nasal cavity does not exclude deep disease. Microbiology Mucorales and Aspergillus account for most disease; Rhizopus is prominent among Mucorales. Tissue diagnosis is necessary because first-line antifungal choice differs substantially. Surgery Endoscopic sinonasal debridement is consistently associated with better source control; repeated debridement may be required. Do not delay surgery while waiting for complete culture speciation when histopathology/clinical evidence is compelling. Orbit management Exenteration is not automatically required for all orbital involvement; benefit is more plausible in advanced/progressive disease. Use stage-, vision-, apex-, and CNS-based multidisciplinary decision-making. Local amphotericin TRAMB may reduce exenteration in localized orbital disease; comparative evidence is low certainty. Consider as adjunct, not replacement, for systemic therapy and sinonasal debridement. Prognosis Intracranial extension, altered consciousness, DKA, advanced stage, and delayed treatment predict worse outcome. Escalate multidisciplinary care early before orbital-apical or CNS progression. Risk of Bias Most included studies were retrospective and were vulnerable to confounding by disease severity and treatment selection. Patients undergoing exenteration or extensive surgery generally had more advanced disease, making crude outcome comparisons misleading. Microbiological ascertainment varied because some centers required positive culture, whereas others accepted histopathological evidence with compatible imaging. Follow-up was incomplete in several COVID-era cohorts, and visual outcomes were not uniformly defined. Table 4. Overall risk-of-bias summary. Overall risk-of-bias concern Studies, n Typical limitations Low 2 Clear case definitions, consecutive enrollment, structured outcome ascertainment Moderate 8 Retrospective design, incomplete adjustment, heterogeneous treatment thresholds High 3 Strong selection bias, incomplete follow-up, unclear microbiological or treatment ascertainment Certainty of Evidence Table 5. Certainty of evidence for major clinical questions. Question Certainty Interpretation Clinical red flags for orbital/CNS extension Moderate Multiple cohorts show consistent association of visual loss, ophthalmoplegia, altered consciousness, and advanced imaging findings with severe disease. Dominance of Mucorales and Aspergillus Moderate Consistent across microbiological series, but culture sensitivity and taxonomy vary. Benefit of combined systemic antifungal therapy plus sinonasal debridement Moderate Strong clinical consistency despite absence of randomized trials. Routine benefit of orbital exenteration Low Profound confounding by indication; benefit appears stage-dependent. Benefit of retrobulbar amphotericin B Low Promising observational comparative data, but heterogeneous protocols and patient selection. Isavuconazole/posaconazole as alternatives or step-down for mucormycosis Low–moderate Supported by nonrandomized trials, registries, and guideline synthesis; rhino-orbital-specific comparative data are limited.

This review shows that the term “rhino-orbital infection” in the immunocompromised population largely represents an invasive fungal emergency rather than routine bacterial orbital cellulitis. Mucorales and Aspergillus dominate the microbiological spectrum, and their relative distribution depends heavily on the host. Diabetes, ketoacidosis, and corticosteroid exposure favor mucormycosis, whereas prolonged neutropenia and hematologic malignancy are prominent in invasive aspergillosis. The COVID-associated mucormycosis epidemic changed the scale but not the fundamental biology of the disease. The COSMIC study demonstrated the convergence of diabetes and corticosteroid exposure on a massive scale, while also showing that outcomes can improve when clinicians recognize stage-specific disease and combine amphotericin B with timely sinus surgery. The very large sample size also highlighted that orbital involvement is common but does not automatically mandate exenteration.A critical finding is that orbit and vision are not equivalent outcomes. Globe salvage does not ensure useful vision, because angioinvasion can cause irreversible optic-nerve or retinal vascular ischemia before infection is controlled. Conversely, a blind but anatomically preserved eye may still provide major cosmetic and psychological benefit. Future studies should therefore report survival, fungal control, globe preservation, and functional visual outcome separately. Treatment comparisons must be interpreted cautiously. Exenteration cohorts are enriched for severe disease, and survival after exenteration cannot be compared directly with survival after conservative treatment without adjustment for stage. The same applies to retrobulbar amphotericin: patients selected for local injection often have potentially salvageable orbital disease. The Dallalzadeh multicenter study provides important comparative evidence but does not eliminate treatment-selection bias. Microbiology remains central to management. Empiric liposomal amphotericin B is appropriate when mucormycosis is strongly suspected because delay can be catastrophic and voriconazole lacks reliable activity against Mucorales. However, histopathology and culture should be pursued urgently because invasive Aspergillus requires a different pharmacologic strategy. Molecular methods and MALDI-TOF can improve species identification, particularly when cultures are negative or mixed infection is suspected. The literature also exposes an evidence gap in non-fungal rhino-orbital infection among immunocompromised hosts. Bacterial co-infection is clinically relevant, especially in necrotic tissue and prolonged hospitalization, but most studies do not report bacterial organisms systematically. Future prospective registries should capture bacterial and fungal microbiology together rather than treating them as mutually exclusive categories. Clinical Management Framework For an immunocompromised patient with new facial or orbital pain, visual change, ophthalmoplegia, proptosis, ptosis, palatal or nasal necrosis, or cranial neuropathy, the recommended clinical sequence is rapid stabilization and reversal of modifiable host factors; urgent ENT and ophthalmology examination with nasal endoscopy; immediate biopsy from suspicious viable-edge tissue; fungal microscopy, histopathology, bacterial and fungal culture, and species-level identification where possible; contrast-enhanced CT and preferably MRI when orbital apex, cavernous sinus, vascular, or cerebral spread is suspected; immediate mold-active therapy tailored to the most likely organism; and prompt endoscopic source control. Orbital intervention should then be individualized according to vision, radiological stage, progression, response to treatment, and CNS involvement. Strengths This review integrates otorhinolaryngology, ophthalmology, microbiology, infectious-disease, and surgical evidence rather than examining mucormycosis treatment alone. It explicitly compares host profiles and organism patterns, separates survival from globe and visual outcomes, and incorporates large COVID-era datasets together with pre-COVID invasive fungal rhinosinusitis cohorts. Limitations The evidence base is dominated by retrospective studies, and randomized trials are not feasible for many surgical questions. Definitions of orbital involvement, microbiological confirmation, treatment response, and visual outcome varied. COVID-associated cohorts may not generalize fully to neutropenic or transplant populations. The review also encountered limited separable data on bacterial rhino-orbital infection, making the synthesis primarily reflective of invasive fungal disease. Treatment-selection bias is especially important when interpreting exenteration and local amphotericin outcomes. Finally, study-level meta-analysis was not performed because of marked heterogeneity. Future Research Prospective multicenter registries should use uniform definitions of AIFRS, orbital stage, microbiological certainty, antifungal exposure, surgical extent, globe salvage, best-corrected visual acuity, neurological complications, and 30- and 90-day mortality. Comparative studies of stage-matched orbit preservation versus exenteration are needed, as are standardized trials or target-trial emulations of retrobulbar amphotericin B. Molecular fungal diagnostics, circulating Mucorales DNA, metagenomic sequencing, and rapid species identification should be evaluated for their ability to shorten time to targeted therapy. Research should also address mixed bacterial-fungal infection and antifungal resistance.

Rhino-orbital infection in immunocompromised patients is predominantly an acute invasive fungal syndrome caused by Mucorales and Aspergillus. Diabetes, diabetic ketoacidosis, hematologic malignancy, neutropenia, transplantation, and corticosteroid exposure define the major risk states. Orbital pain, ophthalmoplegia, visual loss, ptosis, facial numbness, necrosis, and altered consciousness are high-risk clinical features. Mucorales appear more strongly associated with aggressive orbital and cranial-nerve disease, while Aspergillus remains especially important in neutropenic and hematologic-malignancy populations. Optimal care requires immediate tissue diagnosis, pathogen-directed systemic antifungal therapy, early endoscopic sinonasal debridement, and reversal of modifiable host factors. Orbital exenteration should not be automatic for all orbital involvement; it is best reserved for selected advanced or progressive disease. Retrobulbar amphotericin B offers a promising globe-preserving adjunct in localized orbital mucormycosis, but comparative certainty remains low. Intracranial extension, altered consciousness, DKA, and delayed treatment remain the clearest markers of poor outcome.

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