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Research Article | Volume 11 Issue 4 (April, 2025) | Pages 522 - 528
Pattern of Ophthalmic Involvement in Rhino-orbital Mucormycosis following COVID-19 infection: A Cross-sectional study
 ,
 ,
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1
Associate Professor, Department of Ophthalmology, Govt Medical College and Hospital, Wanaparthy, Telangana
2
Associate Professor, Department of Ophthalmology, Govt medical College and Hospital, Jagityal, Telangana
3
Associate Professor, Department of Ophthalmology, Government Medical College, Yadadri Bhuvanagiri, Dist. Yadadri, Telangana
4
Associate Professor, Department of Ophthalmology, Government Medical College Jogulamba Gadwal, Telangana
Under a Creative Commons license
Open Access
Received
March 10, 2025
Revised
March 25, 2025
Accepted
April 10, 2025
Published
April 24, 2025
Abstract

Background: Rhino-orbital mucormycosis, a rare but aggressive fungal infection, saw a surge during the COVID-19 pandemic, particularly in individuals with diabetes and those treated with corticosteroids. This study aims to investigate the pattern of ophthalmic involvement in patients who developed mucormycosis in the context of COVID-19. Understanding the specific ways this infection manifests in the eye is crucial for early diagnosis, appropriate management, and potentially improving outcomes for this vulnerable patient population. Methods: A total of 443 patients diagnosed with mucormycosis in the post-COVID-19 setting were included in the study. All patients had microbiologically or radiologically confirmed mucormycosis and a history of recent COVID-19 infection (confirmed by RT-PCR or rapid antigen test. All patients underwent a comprehensive evaluation by a multidisciplinary team consisting of Ophthalmologists, ENT Surgeons, Neurologists, and Infectious Disease Specialists. Data was collected regarding the age, gender, history of COVID-19, severity, duration of hospitalization, use of steroids and oxygen therapy. The history of Pre-existing diabetes, insulin dependence, and newly diagnosed (de novo) diabetes post-COVID. Results: In this study of 443 COVID-19-associated mucormycosis cases, 68% were male and the majority (65.9%) were aged between 41–60 years. Diabetes was present in 57.7% and 29.6% had newly diagnosed diabetes post-COVID. Most patients (87.1%) were unvaccinated, and mucormycosis onset occurred 31–70 days post-COVID in 68% of cases. Ophthalmic involvement was predominantly rhino-orbital (79%), with vision loss observed in 35.8% of orbital cases. Common ocular findings included CRAO (12.5%) and diabetic retinopathy (17.2%). These findings highlight the aggressive ophthalmic presentation and emphasize the need for early screening and intervention in high-risk, post-COVID-19 individuals. Conclusion: In the present study we found that there is a significant ophthalmic burden of mucormycosis in post-COVID-19 patients, particularly among diabetic, unvaccinated, and middle-aged male populations. Most of the cases in this study were with rhino-orbital involvement, and a substantial number had irreversible vision loss due to CRAO, optic atrophy, or extensive orbital spread. These findings show the importance of early ophthalmic evaluation in patients with COVID-19-associated mucormycosis.

Keywords
INTRODUCTION

The outbreak of coronavirus disease 2019 (COVID-19) which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a significant challenge to the healthcare system across the world. The respiratory illness nature of COVID-19 present initially soon shifted to multisystem involvement which includes thromboembolism and cytokine storm along with secondary infections from immunosuppression [1]. The second wave of the pandemic in India witnessed mucormycosis emerge as a serious opportunistic infection due to its nature of being an aggressive angioinvasive fungal infection [2]. Mucormycosis develops from fungi within the Mucorales order which are mainly Rhizopus species. Healthcare professionals identify this condition in people with weakened immune systems because its fast development leads to death in cases where patients do not get proper diagnosis and treatment [3]. The COVID-19 pandemic reported extensive occurrence of the disease in patients who have diabetes mellitus along with those who receive systemic corticosteroids and extended hospital stays or require oxygen therapy [4, 5]. The number of COVID-19-associated mucormycosis (CAM) cases in India escalated rapidly during the pandemic peak which led the health authorities to designate it as a reportable disease [6]. Mucormycosis-related disease of the eyes appears most severely as rhino-orbital or rhino-orbito-cerebral mucormycosis (ROCM). The infection starts in the sinuses before spreading rapidly into the orbit and central nervous system by blood vessels which results in proptosis and vision loss progressing toward fatal outcomes [7]. The pathogenic quality of the fungal invasion through blood vessels results in tissue death and clot formation therefore an early diagnosis becomes essential. The initial clinical sign often appears in the orbital area due to which both treatment immediate response and disease outcome depend on this presentation. Multiple causative factors contribute to the connection between COVID-19 and mucormycosis development. Among the primary contributors to mucormycosis development are preexisting hyperglycemia along with newly identified diabetes and the weakened immune response from corticosteroids together with each virus's effects on the body [8]. Several conditions such as hypoxia combined with iron overload metabolic acidosis and phagocytic dysfunction in COVID-19 patients promote fungal growth in their bodies [9]. The protection provided by vaccinations remains under investigation to determine its effectiveness in preventing CAM symptoms [10]. Research about the clinical manifestation and treatment of coronavirus disease 2019-associated mucormycosis exists as case series but detailed assessments of ophthalmic complications are scarce. A thorough comprehension of the disorders affecting eyes along with definitions of how much the infection spreads through the orbit and central nervous system will help teams deliver prompt multidisciplinary care during early recognition of this condition. The current study aimed to analyze the demographic profile, diabetic status, COVID-19 vaccination status, duration of mucormycosis onset, and detailed ophthalmic findings in patients presenting with mucormycosis following COVID-19 infection. The results of this study can provide an understanding of clinical patterns of ophthalmic involvement and also help in formulating strategies to preserve vision and reduce morbidity in high-risk groups.

MATERIALS AND METHODS

This cross-sectional observational study was done in the Department of Ophthalmology, Gandhi Medical College and Hospital, Secunderabad, Telangana. Institutional ethical approval was obtained for the study. Written consent was obtained from all the participants of the study after explaining the nature of the study in vernacular language.

 

Inclusion Criteria

  1. Patients aged 18 years and above.
  2. Males and females
  3. Confirmed history of COVID-19 infection within the previous 3 months.
  4. Clinical, radiological, or microbiological diagnosis of mucormycosis.
  5. Presence of ophthalmic signs and symptoms attributable to mucormycosis.

 

Exclusion Criteria

  1. Patients with incomplete clinical records or follow-up.
  2. Patients with pre-existing ocular pathologies not related to mucormycosis.
  3. Patients are unwilling to provide informed consent.

 

A total of 443 patients diagnosed with mucormycosis in the post-COVID-19 setting were included in the study. All patients had microbiologically or radiologically confirmed mucormycosis and a history of recent COVID-19 infection (confirmed by RT-PCR or rapid antigen test).

 

Data Collection:

All patients underwent a comprehensive evaluation by a multidisciplinary team consisting of ophthalmologists, ENT surgeons, neurologists, and infectious disease specialists. Data was collected regarding the age, gender, history of COVID-19, severity, duration of hospitalization, use of steroids and oxygen therapy. The history of Pre-existing diabetes, insulin dependence, and newly diagnosed (de novo) diabetes post-COVID.  Vaccination Status recorded was whether the patient had received one or both doses of COVID-19 vaccine. The onset of Mucormycosis was recorded with a duration between COVID-19 recovery and the onset of mucormycosis symptoms. Every patient underwent nasal wash. Samples of nasal wash were sent for microbiological examination. A biopsy was taken from the appropriate disease's site and samples were sent to the Department of Microbiology and Pathology. KOH mount preparation and culture were done in SDA (Sabourd Dextrose Agar media) for fungus and in blood agar medium.

 

Ophthalmic Evaluation:

All the patients underwent a thorough ocular examination. This included an assessment of visual acuity using Snellen’s chart. Anterior segment evaluation was done with slit lamp biomicroscopy for conjunctival injection, proptosis, corneal changes, anterior chamber reaction, and pupillary abnormalities. The Posterior segment evaluation using direct and indirect ophthalmoscopy, and fundus photography where feasible. Orbital imaging (contrast-enhanced CT or MRI) was performed in all cases to assess the extent of disease, including involvement of paranasal sinuses, orbit, and brain. All the cases with orbital involvement were given periocular injection of Amphotericin B to limit disease progression and preserve ocular structures. 1 ml of liposomal Amphotericin B (3.5 mg/ml) is injected retrobulbarly every 48–72 hours, with the number of injections tailored based on clinical response and imaging findings.

 

Statistical Analysis:

All the available data were entered in Microsoft Excel and analyzed using SPSS version 23.0 (IBM Corp, Armonk, NY). The continuous variables were represented as frequency, mean, standard deviation, and percentages. The categorical variables were calculated using Pearson's Chi-square test and the values of p <0.05 were considered statistically significant.

 

RESULTS

A total of 443 covid 19 cases were included in the study based on the inclusion and exclusion criteria. Table 1 shows that mucormycosis with ophthalmic involvement post-COVID-19 affected predominantly males (68%). Most patients were between 41–60 years old (65.9%), indicating a higher vulnerability in middle-aged adults, possibly due to metabolic disorders such as diabetes that compromise immunity. The minimal involvement in younger age groups and absence in patients over 80 may reflect either a lower incidence in the elderly due to mortality or underreporting. This age and gender trend is consistent with previously reported patterns in mucormycosis cases during the COVID-19 pandemic.

Table 1: Demographic Characteristics (n=443)

Parameter

Number (%)

Gender

- Male

301 (68.0%)

- Female

142 (32.0%)

Age Distribution in years

11 – 20  

1 (0.3%)

21 – 30  

12 (3.0%)

31 – 40  

57 (14.4%)

41 – 50  

132 (33.3%)

51 – 60  

129 (32.6%)

61 – 70  

47 (1 1.9%)

 71 – 80  

18 (4.5%)

>80

0

 

Table 2 demonstrates the diabetic status among patients evaluated for diabetic status, 51.8% had non-insulin-dependent diabetes mellitus (NIDDM), 8.2% were insulin-dependent (IDDM), and notably, 29.6% developed de novo diabetes, likely triggered by COVID-19 or steroid use. De novo diabetes was most common in patients aged 41–60 years, emphasizing the role of acute hyperglycemia as a significant risk factor in mucormycosis development. Only 10.5% of cases had no diabetes, underscoring the pathogenetic link between uncontrolled glycemic states and mucormycosis.

Table 2: Diabetic Status and De Novo Diabetes Age Distribution

Parameter

Number (%)

Diabetic Status (n=257)

NIDDM

133 (51.8%)

IDDM

21 (8.2%)

De Novo Diabetes

76 (29.6%)

No Diabetes

27 (10.5%)

Age in years De Novo DM (n=47)

21 – 30   

1 (2.1%)

31 – 40  

8 (17.0%)

41 – 50

15 (31.9%)

 51 —60

12 (25.5%)

61—70

8 (17.0%)

71 —80

2 (4.3%)

>80 years

1 (2.1%)

 

Table 3 shows the vaccination status and duration of mucormycosis onset in the cases of the study. Among 422 studied patients, we identified 87.1% were not vaccinated for COVID-19 which implies that vaccine status appears linked to severe post-COVID conditions such as mucormycosis. The data demonstrates that fully vaccinated patients numbered only 2.1% of total cases since vaccination can potentially guard against such infections. Mucormycosis showed its initial symptoms within the period of 51–70 days following COVID infection in 36.8% of patients while 27.2% of patients experienced symptoms after 70 days. Patients who appear to recover from COVID-19 need extended monitoring because symptoms emerge weeks following initial recovery.

Table 3: COVID-19 Vaccination Status and Duration of Mucormycosis Onset

Parameter

Number (%)

Vaccination Status (n=194)

- Unvaccinated

169 (87.1%)

- Partially Vaccinated

21 (10.8%)

- Fully Vaccinated

4 (2.1%)

Onset post-COVID (n=136)

- 21-30 days

6 (4.4%)

- 31—40 days

19 (14.0%)

- 41—50 days

24 (17.6%)

- 51-70 days

50 (36.8%)

- > 70 days

37 (27.2%)

 

Table 4 depicts the pattern of ophthalmic involvement in the cases. The results show that the majority of patients (79%) had paranasal sinus (PNS) and orbital involvement, indicating the typical spread of mucormycosis from the sinuses into the orbit. A smaller subset exhibited more extensive spread including the palate and central nervous system (CNS), reflecting severe disease progression. Rare presentations involved isolated pulmonary or CNS involvement. These findings emphasize the angioinvasive nature of mucormycosis and the importance of early detection before orbital or intracranial extension occurs.

Table 4: Patterns of Ophthalmic Involvement (n=443)

Site of Involvement

Number (%)

- PNS + Orbit

350 (79.0%)

- PNS + Palate + Orbit

22 (5.0%)

- Orbit + CNS

49 (1 1.196)

- Orbit + Palate + CNS

16 (3.6%)

- Only Pulmonary

5 (1.1%)

- CNS without Orbit

3 (0.7%)

- Palate + PNS

11 (2.5%)

Table 5 demonstrates that in 145 cases out of 443 cases, 64.1% retained vision better than counting fingers at 2 meters, while 35.8% had poor or no perception of light, indicating severe optic nerve or retinal involvement. Anterior segment findings were rare. Posterior segment involvement included diabetic retinopathy (17.2%), central retinal artery occlusion (CRAO, 12.5%), and optic atrophy (4.7%), underscoring ischemic damage from angioinvasion. A normal fundus in 35.2% suggests variable disease extent, emphasizing individualized clinical evaluation.

Table 5: Ocular Findings (n=443)

Parameter

Number (%)

Vision in Orbital Cases (n=145)

>CF 2m

93 (64.1%)

CF 2m to PL +ve

26 (17.9%)

PL -ve

26 (17.9%)

Anterior Segment

 

Corneal Involvement

7 (1.6%)

AC Exudates

1 (0.2%)

Posterior Segment (n=128)

Optic Atrophy

6 (4.7%)

CRAO

16 (12.5%)

CRVO

5 (3.9%)

Diabetic Retinopathy

22 (17.2%)

Normal Fundus

45 (35.2%)

DISCUSSION

The COVID-19 pandemic has caused an increase in secondary infections with mucormycosis being the main reported secondary infection, especially in the Indian subcontinent. The aggressive angioinvasive fungal infection Mucormycosis usually occurs among immunocompromised patients through rapid dissemination that particularly affects paranasal sinuses and orbits thus causing severe ophthalmic complications. The study aimed to identify the clinical pattern of ophthalmic involvement in patients who developed mucormycosis following COVID-19 infection. Among our patient cohort of n=443 cases out of which n=301(68%) were males cases while females made up n=142 (32%) of cases which matches findings from previous studies and may indicate gender susceptibility to mucormycosis [11, 12]. The majority of patients who developed mucormycosis were within the 41-60 years age range constituting over 65% of cases. This could be due to their susceptibility to pre-existing health conditions alongside their increased use of corticosteroids for managing COVID-19 symptoms. This study demonstrated a strong association between diabetes mellitus and mucormycosis pathogenesis. In this study, 57.7% had pre-existing diabetes, and an additional 29.6% developed de novo diabetes post-COVID-19. Clinical reports indicate that mucormycosis develops more frequently when patients have high blood-glucose levels particularly when treated with corticosteroids leading to fungus growth and decreased immune functions [13]. The phagocytic function maintains a strong connection with uncontrolled glycemic status which enables mucor to invade more easily [14]. The study of the vaccination status of our cohort revealed that the majority (87.1%) of affected individuals were unvaccinated. While vaccination may not directly prevent mucormycosis however, it reduces the severity of COVID-19 and can indirectly reduce the use of immunosuppressive drugs or steroids, and decreases overall hospitalization which are the risk factors for fungal infections [15]. We found that the majority of mucormycosis cases in this study presented to the hospital within 31 – 70 days post-COVID, indicating a period of vulnerability in the convalescent phase. There could be ongoing immune dysregulation which may predispose patients to secondary fungal infections [16]. A majority of 79% presented with rhino-orbital mucormycosis when ophthalmic involvement occurred. The invasive nature of the infection revealed itself through CNS involvement which affected 14.8% of the total cases. Visual loss was a frequent sign in orbital infections because approximately 35.8% of patients in this group had vision degeneration and 17.9% experienced total vision loss. The presence of central retinal artery occlusion and optic atrophy in posterior segments indicates vascular and neural deterioration which is characteristic of mucor-mediated orbital invasion [17]. Various clinical tests established that normal fundus appearance existed in just 35.2% of patients demonstrating how severe the infection had damaged their eyes. Previous research has confirmed that rhino-orbital-cerebral mucormycosis leads to severe complications that progress quickly [18]. Therefore, our study highlights the need for early ophthalmic screening in high-risk post-COVID patients especially those with prolonged corticosteroid use or with diabetes mellitus. Rapid diagnosis imaging and timely antifungal therapy, often combined with surgical debridement remain the cornerstone of management.

CONCLUSION

Within the limitations of the present study, we found that there is a significant ophthalmic burden of mucormycosis in post-COVID-19 patients, particularly among diabetic, unvaccinated, and middle-aged male populations. Most of the cases in this study were with rhino-orbital involvement, and a substantial number had irreversible vision loss due to CRAO, optic atrophy, or extensive orbital spread. These findings show the importance of early ophthalmic evaluation in patients with COVID-19-associated mucormycosis. It also stresses the importance of post-infection monitoring especially in high-risk patients. Therefore, enhancing public health strategies focusing on glycemic control, judicious steroid use, and COVID-19 vaccination could reduce the incidence and severity of mucormycosis and its associated visual morbidity.

REFERENCES
  1. Gupta A, Madhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID-19. Nat Med. 2020;26(7):1017-1032.
  2. John TM, Jacob CN, Kontoyiannis DP. When uncontrolled diabetes mellitus and severe COVID-19 converge: the perfect storm for mucormycosis. J Fungi (Basel). 2021;7(4):298.
  3. Spellberg B, Edwards J Jr, Ibrahim A. Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clin Microbiol Rev. 2005;18(3):556-569.
  4. Mehta S, Pandey A. Rhino-orbital mucormycosis associated with COVID-19. Cureus. 2020;12(9): e10726.
  5. Singh AK, Singh R, Joshi SR, Misra A. Mucormycosis in COVID-19: a systematic review of cases reported worldwide and in India. Diabetes Metab Syndr. 2021;15(4):102146.
  6. Ministry of Health and Family Welfare, India. Advisory on COVID-19-associated mucormycosis. Available from https://ncdc.mohfw.gov.in/wp-content/uploads/2024/04/CD-Alert-Covid-19-Associated-Mucormycosis-July-2021.pdf  [Accessed 22nd Aug 2023]
  7. Sharma S, Grover M, Bhargava S, et al. Post coronavirus disease mucormycosis: a deadly addition to the pandemic spectrum. J Laryngol Otol. 2021;135(5):442-447.
  8. Pal R, Singh B, Bhadada SK, et al. COVID-19-associated mucormycosis: An updated systematic review of the literature. Mycoses. 2021;64(12):1452-1459.
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  10. Moorthy A, Gaikwad R, Krishna S, et al. SARS-CoV-2, Uncontrolled Diabetes and Corticosteroids - An Unholy Trinity in Invasive Fungal Infections of the Maxillofacial Region? A Retrospective, Multicentric Analysis. J Maxillofac Oral Surg. 2021;20(3):418–425.
  11. Sen M, et al. Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India. Mycoses. 2021;64(9):1238-1252.
  12. Mehta S, Pandey A. Rhino-Orbital Mucormycosis Associated With COVID-19. Cureus. 2020;12(9):e10726.
  13. John TM, Jacob CN, Kontoyiannis DP. When uncontrolled diabetes mellitus and severe COVID-19 converge: The perfect storm for mucormycosis. J Fungi (Basel). 2021;7(4):298.
  14. Roden MM, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41(5):634-653.
  15. Singh AK, et al. Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India. Diabetes Metab Syndr. 2021;15(4):102146.
  16. Pal R, et al. COVID-19-associated mucormycosis: An updated systematic review of the literature. Mycoses. 2021;64(12):1452-1459.
  17. Werthman-Ehrenreich A. Mucormycosis with orbital compartment syndrome in a patient with COVID-19. Am J Emerg Med. 2021; 42: 264. e5-264.e8.
  18. Sharma S, Grover M, Bhargava S, Samdani S, Kataria T. Post coronavirus disease mucormycosis: a deadly addition to the pandemic spectrum. J Laryngol Otol. 2021;135(5):442-447.

 

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