B S Abhishakth Gerhardt¹, Bhuvaneshwari^2*, Sravani Marpaka³

¹Post Graduate ,²Associate Professor, Department of Pharmacology, Osmania Medical College, Telangana, INDIA.

³Patient Safety Pharmacovigilance Associate, PvPI, AMC-Osmania Medical College, Telangana, INDIA.

Email:bhuvana2005@gmail.com

The graph-3 and table-4 depicts that 21 patients (70%) out of 30 responded favorably to Natamycin as primary treatment in terms of visual acuity. On statistical analysis p value is found to be 0.0021 which is significant. Out of 9 patients with central corneal ulcer, for 3 patients visual acuity has improved from 3 meters to 6/60 and in 4 patients it is improved from 5 meters to 6/36 .Remaining 2 patients did not respond in terms of visual acuity but they responded in other clinical features. 14 with peripheral corneal ulcer responded favorably to topical Natamycin and visual acuity has improved from 6/60 to 6/24 in 7 patients, 6/36 to 6/18 in 4 patients and 6/60 to 6/18 in 3 patients. 3 patients who had large corneal ulcer with perforation and melting did not respond to Natamycin, were taken for keratoplasty. In 4 patients debridement for slough was done and then they were started with 5% Natamycin. They had a favorable response. In 23 out of 30 patients ulcer margin receded, size of hypopyon reduced and satellite lesions reduced. There were no adverse drug reactions observed and reported by patients during the indexed period of the study.

DISCUSSION

In our study male predominance (60%) is observed. Majority of patients are from rural areas. By occupation most of them are farmers and few are house wives. Majority had history of trauma or foreign body like vegetable matter that was encountered at work place. Patients presented with history of insidious onset of symptoms which were gradual in progression. A complete ocular examination and clinical evaluation was done for clinical diagnosis. A simpler and rapid diagnostic test, KOH mount was used as a screening test for fungal elements detection. KOH mount showed positive result in 70% of study population. Though culture results may play a vital role to initiate medical therapy in infectious diseases, fungi grow slower than other pathogens⁹. Here comes the need for proper history, clinical examination, screening tests like KOH smear and confocalmicroscopy which shows fungal elements at a faster rate¹⁰. Based on the above observations we started the anti-fungal treatment as it will be too late if we wait for the culture results. There are three main classes of antifungal agents that are used for treatment of fungal corneal ulcer which are polyenes, triazoles and echinocandins. Our study drug Natamycin, an antifungal agent is chemically a tetraene polyene. Its mechanism of action is by blocking fungal growth by binding specifically to ergosterol which is an essential component in fungal cell wall¹¹.As it has low ocular retention, frequent administration of is advised¹². On topical application Natamycin enters only into corneal stroma but not into ocular fluid¹³. Hence it is primarily useful in patients with superficial ocular infection. Conventional route of administration of antifungal agents in fungal corneal ulcer is in the form of eye drops. Systematic use of the agents possesses serious side effects. Other routes include oral, intravenous, ointment, subconjunctival and corneal stromal injection. With Natamycin intravenous and subconjunctival injections it’s difficult to achieve therapeutic levels and it poorly penetrates into the aqueous⁶. Natamycin has broad antifungal spectrum against filamentous fungi especially Fusarium species¹². In our study we considered visual acuity as the primary outcome in respect to effectiveness of Natamycin. The data was statistically evaluated with IBM SPSS statistics for Windows, Version 22.0. When we compare mean visual acuity before and after Natamycin treatment it is observed that Natamycin showed favorable response in 70% (21 out of 30) of patients with an improved visual acuity with a p=0.0021, which implies it’s statistically significant. In peripheral corneal ulcer patients Natamycin showed favorable response with p= <0.001 and in central corneal ulcer patients showed favorable response with p= 0.001 which also implies its statistical significance. Due to the means of the visual acuity and the direction of t-value, we can conclude that there was a statistically¹⁴ significant improvement in visual acuity following the drug. Another study by Sharma et.al. also stated significant improvement in visual acuity (p=0.005) with Natamycin in patients with Fusarium keratitis and 89.2% patients showed ulcer healing¹⁵. We consider the progression of ulcer and drug safety as secondary outcome. In 77% (23 out of 30) of patients ulcer margin receded, size of hypopyon reduced and satellite lesions reduced. None of the patients developed adverse drug reactions during the indexed period. From the above analysis we can conclude that pharmacotherapy with topical 5% Natamycin is effective both clinically and statistically. Consider central and peripheral corneal ulcers as non severe keratitis (23 out of 30) and large corneal ulcer with perforation and ulcer with slough as severe keratitis(7 out of 30). Among non-severe keratitis 91% (21 among 23) showed improvement in vision with best spectacle-corrected visual acuity. This tells high the efficacy of Natamycin in early and less severe cases. A study done by Kalavathy et.al. also stated 72% (36 of 50) patients showed a favorable response to primary Natamycin therapy among them 28 out of 37 are non severe keratitis, 8 out of 13 are with severe keratitis¹⁶. There are also comparative studies of Natamycin with voriconazole. In a study by Venkatesh Pragna et al states significantly better clinical and microbiological outcomes with Natamycin than voriconazole treatment for smear-positive filamentous fungal keratitis¹⁷.The efficacy of Natamycin is attributed to its broad spectrum of antifungal activity and safety profile. The primary effect of 5% Natamycin in the management of fungal corneal ulcer is prevention of disease progression that may lead to vision loss or blindness and morbidity of eye. The vision improvement attained as Best spectacular corrected visual acuity may be achieved around 3 months post treatment. Generally side effects of Natamycin are rare, but there may be allergic reactions like ocular irritation ¹³.This study brings out the requirement of the patient to seek medical attention as early as possible .We are also emphasizing the importance of creating awareness among the general population regarding need for taking precautionary measures for avoiding foreign body or trauma to the eye.

CONCLUSION

An early medical intervention with topical 5% Natamycin can prevent ocular morbidity and blindness to a great extent. Clinical findings and rapid diagnostic tests like KOH smear are helpful in early detection for timely management of disease. 5% topical Natamycin is a preferable choice as a primary first line management in superficial fungal ocular infection. More rapid, sensitive and specific diagnostic tests for the detection of fungal corneal ulcer, study of more topical ophthalmic antifungal agents and comparative studies are always helpful for better management.

ACKNOWLEDGMENT

We are thankful to Dr.M.Padma , Associate Professor, Sarojini Devi Eye Hospital, for helping us to conduct the study in this institution. We also thank the patients of Sarojini Devi  Eye Hospital, for their cooperation.

REFERENCES