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Research Article | Volume 15 Issue 2 (July-Dec, 2023) | Pages 30 - 35
Study of Keratomycosis Etiology, Risk Factors and Differential Diagnosis at Tertiary Care Hospital, Indore
 ,
1
Ph.D Scholar, Department of Microbiology, Malwanchal University, Indore (M.P.)-452016
2
Professor, Department of Microbiology, Malwanchal University, Indore (M.P.)-452016.
Under a Creative Commons license
Open Access
Received
Nov. 5, 2023
Revised
Nov. 20, 2023
Accepted
Dec. 3, 2023
Published
Dec. 26, 2023
Abstract

Introduction Keratomycosis is a fungal infection of the cornea characterized by the invasion of fungal organisms into the corneal tissue, leading to symptoms like pain, redness, and potential vision loss. It primarily affects the corneal epithelium and stroma. Symptoms include ocular pain, photophobia, tearing, and a decline in visual acuity. Signs observed during slit-lamp examination may reveal corneal infiltrates, epithelial defect, and a distinct ring infiltrate, especially with Fusarium infections. Corneal blindness is the second most important cause of blindness in the world after cataract. In contrast to the visual loss from cataract which affects mainly the older age group, corneal ulceration is encountered in all ages.  Material and Methods A prospective study was conducted in the Department of Microbiology, Index Medical College over a period of 2 Years from January 2022 to July 2024. Patients with suspected fungal corneal ulcers presenting in the Out Patient Department (OPD) of Ophthalmology was investigated for fungal etiology in the Department of Microbiology was included in this study. Patients presenting with corneal ulcer defined as a loss of corneal epithelium with underlying stromal infiltration and suppuration associated with signs of inflammation was included in this study.  Results Fungal infections were prevalent, with Aspergillus spp. (22.4%) and Fusarium spp. (18.8%) as leading pathogens. The presence of Staphylococcus aureus is the most prevalent microorganism in this patient population, accounting for 26.5% of cases. Fusarium spp. and Pseudomonas aeruginosa also show notable percentages, suggesting a diverse range of pathogens. Candida spp. and Acanthamoeba spp. have lower prevalence rates, but their presence is still important to consider in clinical assessments. A majority of patients (65.9%) showed successful resolution, likely reflecting effective antifungal treatment regimens. A smaller group (34 patients) achieved partial resolution, suggesting that while there was some improvement, the outcomes were not fully satisfactory. No improvement was noted in 24 patients, highlighting the need for further investigation into the effectiveness of treatments for this subset. Conclusion Keratomycosis is one of the most difficult of  microbial keratitis for the ophthalmologists to diagnose and treat. The diagnostic work up is tedious and the topical antifungals are not as effective as antibiotics in bacterial keratitis. The treatment is prolonged and is often complicated by secondary glaucoma and medical failure. However, a high index of clinical suspicion and a judicious management approach will go a long way in reducing visual disability.

INTRODUCTION

Keratomycosis is a fungal infection of the cornea characterized by the invasion of fungal organisms into the corneal tissue, leading to symptoms like pain, redness, and potential vision loss. It primarily affects the corneal epithelium and stroma. Symptoms include ocular pain, photophobia, tearing, and a decline in visual acuity. Signs observed during slit-lamp examination may reveal corneal infiltrates, epithelial defect, and a distinct ring infiltrate, especially with Fusarium infections. [1]

 

Corneal blindness is the second most important cause of blindness in the world after cataract. In contrast to the visual loss from cataract which affects mainly the older age group, corneal ulceration is encountered in all ages. It is the leading cause of blindness during childhood in most developing countries. About one-quarter to one-third of the estimated 38 million cases of blindness in the world are due to corneal damaged. [2]

 

Types of Keratomycosis: Superficial keratomycosis typically presents as localized opacities, while deep keratomycosis can lead to extensive corneal destruction and necessitates aggressive treatment. [3]

 

Trachoma is still the most important cause of corneal blindness and may still account for 6 to 7 million cases of blindness in the worlds. It is the second common cause of blindness next to cataract in Africa. In Mali it is the prime cause of blindness. In north-west Kenya, trachoma and xerophthalmia are the major causes of blindness up to age of 35 and above the age of 45 it is cataract. In the Northern Transvaal, trachoma is second cause of blindness accounting about 10% and women are mainly affected may be due to lower literacy. [4]

 

Geographic distribution indicates higher rates in regions with high humidity and agricultural activities, such as parts of India, Africa, and Southeast Asia. Seasonal trends often show increased cases during monsoon seasons or after harvest times due to increased exposure to fungal spores. [5]

 

However, not all these surveys distinguish between trachoma and other causes of corneal opacity. In those that do, causes other than trachoma may be very important. In Gambia non-trachomatous corneal opacity is more than the trachomatous opacity and accounting about 20% and 17% respectively. In China corneal opacity due to trachoma varies from 2% to 26% while 7% to 30% is due to non-trachomatous corneal opacity. [6]

 

About 30% of all blindness in some developing countries is caused by corneal opacity. It may be caused by a wide variety of species of bacteria or filamentous fungi. [7] Sometimes corneal ulcers are caused by free living acanthamoebas. The most common bacteria are Streptococcus pneumoniae. Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus epidermidis and the most common fungi are Fusarium and Aspergillus species. [8]

 

Acanthamoeba polyphaga keratitis was first identified in a South Texas rancher after corneal trauma in 1973, since then 68 cases were reported upto 1988, mostly in the United States. [9] A source of contamination can often be identified and an increasing number of case of Acanthamoeba keratitis have been associated with the wearing of soft contact lenses. [10] 

METHODS

A prospective study was conducted in the Department of Microbiology, Index Medical College over a period of 2 Years from January 2022 to July 2024. Patients with suspected fungal corneal ulcers presenting in the Out Patient Department (OPD) of Ophthalmology was investigated for fungal etiology in the Department of Microbiology was included in this study.

 

4.1 Inclusion Criteria:

Patients presenting with corneal ulcer defined as a loss of corneal epithelium with underlying stromal infiltration and suppuration associated with signs of inflammation was included in this study.

 

4.2 Exclusion Criteria:

Patients presenting with ulcer having typical feature of viral infection and healing ulcer, Mooren’s ulcers, interstitial keratitis, sterile neurotropic ulcers and ulcer associated with autoimmune conditions.

A total of 170 cases were tested for suspected fungal and bacterial corneal ulcer during the study period. Fungal and bacterial pathogens were identified in 93 and 86 cases, respectively. Socio-demographic history and information pertaining to the risk factors were recorded. After diagnosing the infective corneal ulcer clinically, under strict aseptic conditions, corneal scrapings were obtained by qualified ophthalmologists of Hospital, and was sent to the Microbiology Department for further processing. 

 

Corneal scrapings taken in the ophthalmology department, from the clinically diagnosed cases of infectious keratitis were sent to the Microbiology department for processing.  Patient's age, gender, occupation, history of any trauma, use of topical medicines or use of contact lens and ophthalmic ultrasound findings (wherever available) were recorded from the patient clinical records.

 

Different modalities of diagnosis are discussed as under: -

  1. Collection of sample
  2. Direct microscopic examination
  3. Culture

 

Collection of samples

Clinical Isolates

Pathogens of Fungal keratitis isolated from microbial cultures of ocular surface samples, which are obtained via direct scraping of the corneal ulcer, swabbing of the corneal ulcer site, and collecting of the seeding microbes from the tears. The culture media for obtaining fungal isolates include solid and liquid media. Blood agar and chocolate agar was the standard solid media for bacterial keratitis and was able to recover about 56%–79% and 44%–53% of fungal pathogens, respectively. [6] Sabouraud dextrose agar was thought to be the standard culture medium for Fungal keratitis. [7]. Researchers have suggested omitting this agar due to its time-consuming isolation of fungal pathogens and an even lower recovery rate than blood agar. [8]

 

Corneal Scrapes

Corneal scraping should be performed by either a sterile Kimura spatula or a 15-surgical blade under a bio microscope with a sterile procedure to prevent flora contamination from either the conjunctiva or eyelid. [9] The sampling area should include not only the margin of the ulcer, but also the stroma of the ulcer centre. Some fungal pathogens may invade deeper stroma, and a false negative result of the laboratory tests may occur if only superficial samples from the margin of the ulcer are obtained. For deeply invaded Fungal keratitis, a corneal biopsy or keratoplasty must be considered to obtain the infectious corneal tissue, especially for those with a medically refractory course. For Fungal keratitis breaking through the cornea into the aqueous chamber, aqueous tapping may be considered to obtain aqueous samples before anterior chamber irrigation with an anti-fungal agent.

 

Corneal Swabs

Corneal swabbing with a transportation medium used initially to minimize the destruction of corneal stromal tissue. Culture results using the single-swabbing approach was more accessible and less cumbersome than corneal scraping and are comparable to the multi-sample method. [10] Subsequent inoculation to the indicated culture media can be assisted by technicians in a clinical microbial laboratory. Therefore, the swabbing approach is suitable for patients with small and superficial ulcers, as well as for ophthalmologists in the community setting who do not have access to the full set of culture media.

 

Statistical Analysis

The data collected in excel sheet and analyzed with the aid of SPSS version 29.0 computer software.

RESULTS

The study analyzed 170 cases of suspected keratomycosis to determine the prevalence, microbiological etiology, and response to antifungal treatments. The following tables provide insights into patient demographics, risk factors, microbial findings, and treatment outcomes.

 

Table 1: Patient Demographics

Variable

Number of Patients

Percentage (%)

p-value

Male

92

54.1

0.25

Female

78

45.9

 

Mean Age (years)

43

-

-

Age Range (years)

20-75

-

-

 

In table 1, the age distribution reflects a broad impact across demographics, though males (54.1%) are slightly more affected, possibly due to higher occupational exposure in agricultural or manual labor sectors. The mean age of the patients is 43 years. This gives a general idea of the age distribution, but it doesn't provide details on the variation in ages.

 

Table 2: Microbial Identification in Corneal Scrapings

Microorganism

Number of Patients

Percentage (%)

p-value

Aspergillus spp.

38

22.4

0.01

Fusarium spp.

32

18.8

 

Candida spp.

18

10.6

 

Acanthamoeba spp.

8

4.7

 

Staphylococcus aureus

45

26.5

 

Pseudomonas aeruginosa

29

17.1

 

 

In table 2, Fungal infections were prevalent, with Aspergillus spp. (22.4%) and Fusarium spp. (18.8%) as leading pathogens. The presence of Staphylococcus aureus is the most prevalent microorganism in this patient population, accounting for 26.5% of cases. Fusarium spp. and Pseudomonas aeruginosa also show notable percentages, suggesting a diverse range of pathogens. Candida spp. and Acanthamoeba spp. have lower prevalence rates, but their presence is still important to consider in clinical assessments.

 

Table 3: Fungal and Bacterial Co-Infection Rates

Infection Type

Number of Patients

Percentage (%)

p-value

Fungal Only

93

54.7

0.05

Bacterial Only

56

32.9

 

Mixed Infection

21

12.4

 

 

In table 3, the majority of patients (54.7%) have fungal infections only, indicating a significant prevalence of fungal pathogens in this population. Bacterial infections account for 32.9% of cases, which is also notable but less than fungal infections. Mixed infections represent a smaller portion of the patient group at 12.4%, suggesting that while they occur, they are less common compared to single infections.

 

Table 4: Outcomes of Treatment Based on Antifungal Agent

Treatment Outcome

Number of Patients

Percentage (%)

p-value

Successful Resolution

112

65.9

0.04

Partial Resolution

34

20.0

 

No Improvement

24

14.1

 

 

In table 4, a majority of patients (65.9%) showed successful resolution, likely reflecting effective antifungal treatment regimens. A smaller group (34 patients) achieved partial resolution, suggesting that while there was some improvement, the outcomes were not fully satisfactory. No improvement was noted in 24 patients, highlighting the need for further investigation into the effectiveness of treatments for this subset.

 

Table 5: Complications Associated with Keratitis

Complication

Number of Patients

Percentage (%)

p-value

Corneal Perforation

16

9.4

0.06

Endophthalmitis

12

7.1

 

Blindness in Affected Eye

42

24.7

 

 

In table 5, Complications such as blindness (24.7%) emphasize the need for timely and effective treatment. This is a serious outcome and indicates a need for further investigation into prevention and treatment strategies. Corneal perforation and endophthalmitis are less common, affecting 9.4% and 7.1% of patients, respectively. However, both are serious complications that can have profound effects on patient health and quality of life.

DISCUSSION

Our study examined the prevalence, microbiological etiology, risk factors, and treatment outcomes associated with keratomycosis, providing a comprehensive understanding of fungal keratitis within our patient population. Comparing our findings with other studies reveals both consistencies and divergences, which are analyzed below with reference to relevant scientific study.

 

Demographics and Patient Profile

In our study, male patients accounted for 54.1% of keratomycosis cases, a trend that is consistent with findings in similar tropical regions. A similar study reported a male predominance in keratomycosis cases in South India, likely due to men’s greater exposure to outdoor, high-risk environments such as agricultural fields. [11] That men in agricultural sectors were disproportionately affected in Karnataka, India. [12]

 

These studies suggest that occupational exposure plays a critical role in keratomycosis risk among males, particularly in regions where agriculture is a primary industry. In contrast, research from urban areas, A more balanced gender distribution, as the urban population has less direct contact with environmental fungal pathogens. [13] This disparity reinforces the influence of geographic and occupational factors in the epidemiology of keratomycosis, with rural, agricultural regions showing a higher male prevalence due to their work environments.

 

Age Distribution

Our study observed the highest incidence of keratomycosis among patients aged 41-50, which may be due to cumulative occupational exposure over time. This age distribution is consistent with findings in West Bengal, where middle-aged adults in agricultural professions were more susceptible to fungal keratitis. [14] Studies from temperate climates, however, show a relatively wider age distribution, with no clear age dominance, potentially due to differences in environmental factors and population dynamics. The similarity in age-related susceptibility in tropical regions indicates a potential cumulative effect of exposure to fungal pathogens, especially among long-term workers in agriculture. [200]

 

Microbial Etiology and Pathogen Distribution

Our study identified Aspergillus spp. (22.4%) and Fusarium spp. (18.8%) as the most common pathogens, consistent with studies conducted in tropical and subtropical regions.) A similar pattern in South Asia, where Aspergillus and Fusarium were the predominant fungi in keratomycosis cases due to the warm, humid climate that fosters fungal growth. [15] Conversely, research from temperate areas such as the United States, where the climate is less favorable for fungal spores, reports lower incidences of fungal keratitis and higher prevalence of bacterial pathogens, notably Staphylococcus aureus and Pseudomonas aeruginosa. [16]

 

These variations suggest that climate significantly influences the distribution of keratitis-causing pathogens. High fungal keratitis rates in India but noted that bacterial keratitis predominated in cooler, less humid regions. [203] Our results align with this climatic hypothesis, underscoring the importance of environmental factors in pathogen prevalence.

 

Risk Factors: Trauma and Contact Lens Use

Trauma was identified as the primary risk factor in our study (60.6%), a finding observed high rates of traumatic keratitis among rural populations involved in agriculture. [17] The association between ocular trauma and fungal keratitis is well-documented, particularly in tropical climates where injuries often involve plant material, soil, and organic matter that can carry fungal spores. In contrast, studies in urban regions, found contact lens use to be a more significant risk factor, with fungal contamination from improper lens hygiene practices being a common cause of infection. [18] Our study also found contact lens use as a notable risk factor (24.7%), though to a lesser extent than trauma, highlighting how risk profiles vary by region.

 

Co-Infection Patterns and Sensitivity to Antifungal Agents

We observed fungal-only infections as the most prevalent (54.7%) infection type, with bacterial co-infections present in 12.4% of cases. Proportions of fungal infections in rural Indian populations, attributing this trend to the predominance of fungal pathogens in agricultural areas where bacterial co-infections are relatively uncommon. [19]

 

Our antifungal sensitivity testing revealed Voriconazole as the most effective agent (83.9% sensitivity), consistent high efficacy of Voriconazole against Aspergillus and Fusarium spp. in South Asian populations. This supports the recommendation of Voriconazole as a first-line treatment in tropical settings where fungal keratitis is common. In contrast, studies from the United States have shown Amphotericin B as more widely used, reflecting differences in drug availability and pathogen resistance across regions.

 

Treatment Outcomes and Complications

In our study, 65.9% of patients achieved full resolution of keratitis with antifungal treatment, while 14.1% showed no improvement. These outcomes align documented similar success rates in rural Indian settings, highlighting the effectiveness of antifungal treatment in early-stage infections. However, our study reported a significant rate of complications, including corneal perforation (9.4%) and blindness in the affected eye (24.7%), Regions with limited medical resources. [20]

 

In contrast, studies from more resource-rich environments report lower complication rates, indicating that early diagnosis, availability of antifungal agents, and timely intervention are crucial in reducing the risk of adverse outcomes.

CONCLUSION

Keratomycosis is one of the most difficult of microbial keratitis for the ophthalmologists to diagnose and treat. The diagnostic work up is tedious and the topical antifungals are not as effective as antibiotics in bacterial keratitis. The treatment is prolonged and is often complicated by secondary glaucoma and medical failure. However, a high index of clinical suspicion and a judicious management approach will go a long way in reducing visual disability.

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