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Research Article | Volume 11 Issue 1 (Jan- Feb, 2025) | Pages 158 - 163
To Study the Efficacy of Azithromycin and Tetracyclines Ophthalmology Eye Drops in Treatment of Meibomitis Related Keratoconjunctivitis at Tertiary Care Hospital
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1
Associate professor, department of Ophthalmology, Mahavir Institute of Medical Sciences, Vikarabad, Telangana, India.
2
Associate professor, Department of Pharmacology, RKDF Medical college Hospital & research centre, Bhopal, Madhya Pradesh, India.
3
Assistant professor, Department of Biochemistry, RKDF Medical College and Hospital. Bhopal. Madhya Pradesh, India.
4
Associate Professor, Department of Pharmacology Varun Arjun Medical College and Rohilkhand Hospital, Shahjahanpur, UP. India
Under a Creative Commons license
Open Access
Received
Nov. 9, 2024
Revised
Nov. 29, 2024
Accepted
Dec. 26, 2024
Published
Jan. 28, 2025
Abstract

Background: Meibomitis-Related Keratoconjunctivitis (MRKC) is typically managed with a combination of antibacterial eye drops and low-dose steroids. Azithromycin hydrate and tetracycline ophthalmic solutions possess both antibacterial and anti-inflammatory properties. This study evaluates the effectiveness of azithromycin hydrate ophthalmic solution as a monotherapy for treating MRKC. Material and Methods: This retrospective study included 197 patients diagnosed with Meibomitis-Related Keratoconjunctivitis (MRKC) who attended the outpatient department of the ophthalmology department at a tertiary care hospital. Approval was obtained from the institutional ethics committee, and all participants provided informed consent. Eligible patients were randomly assigned into two groups using the chit method: Group A (98 patients) received azithromycin, while Group B (99 patients) were treated with tetracyclines. Data collected included patients' sociodemographic details, symptoms, MRKC subtypes, conjunctival hyperemia grade, bulbar conjunctivitis and the percentage of conjunctival vascular curvature. These parameters were recorded at baseline and monitored weekly for five weeks during treatment. Results: In this study, the majority of patients (136; 69.03%) presented with keratoconjunctivitis in both eyes, while 61 patients (30.97%) experienced it in a single eye. Mild vasodilation was the most frequently observed (113; 57.36%), followed by moderate (62; 31.47%), severe (13; 6.59%), and no vasodilation (9; 4.56%). Most patients (146; 74.11%) had the phlyctenular type, while 51 patients (25.88%) exhibited the non-phlyctenular type. Hyperemia was present in the majority of patients (181; 91.87%) and absent in 16 patients (8.12%). Among the 197 patients assessed, conjunctival hyperemia was noted in all (197; 100.00%). Other common symptoms included eye redness (138; 70.05%), watery eyes (129; 65.48%), blurry vision (114; 56.86%), itchy eyes (112; 56.85%), light sensitivity (95; 48.22%), palpebral conjunctiva swelling (75; 38.07%), eyelid margin swelling (71; 36.05%), granulomatous corneal nodules (48; 24.36%), and superficial vascularization (31; 15.73%). At the first visit, groups A and B included 91 and 90 patients, respectively. After one week of treatment (second visit), hyperemia was reduced to 83 patients (91.20%) in group A and 79 patients (87.77%) in group B. By the second week (third visit), reductions were observed in 65 patients (71.42%) in group A and 57 patients (63.33%) in group B. At the third week (fourth visit), 43 patients (47.25%) remained affected in group A and 34 patients (37.77%) in group B. By the fourth week (fifth visit), conjunctival hyperemia was further reduced to 19 patients (20.83%) in group A and 13 patients (14.44%) in group B. Conclusion: Azithromycin showed superior effectiveness in treating meibomitis related keratoconjunctivitis compared to tetracycline

Keywords
INTRODUCTION

Meibomian gland dysfunction (MGD) is the leading cause of dry eye disease, with a prevalence ranging from 3.5% to 70% depending on factors such as age, sex, and ethnicity [1]. A population-based study conducted on Takushima Island, Japan reported an MGD prevalence of 32.9% [2]. MGD is a chronic condition characterized by obstruction of the terminal ducts or changes in the quality or quantity of meibomian gland secretions (meibum)[3]. In obstructive MGD, hyperkeratinisation of the ductal epithelium reduces the availability of meibum, impairing its ability to coat the aqueous layer of the tear film.[4] This deficiency leads to increased tear evaporation, hyperosmolarity, and bacterial overgrowth at the lid margin [5,6].

 

Conservative management of MGD typically includes warm compresses, lid hygiene, meibum expression, and, in severe cases, the use of anti-inflammatory medications [7]. Topical azithromycin has demonstrated efficacy in treating MGD due to its anti-inflammatory and antibacterial properties, which can suppress posterior blepharitis and bacterial growth on the eyelids. Emerging evidence also suggests that azithromycin may directly promote the differentiation of meibomian gland cells and stimulate lipid production, alleviating MGD symptoms [8,9].

 

Azithromycin, a macrolide antibacterial agent, is particularly effective against Cutibacterium acnes. Azithromycin ophthalmic not only exhibits antibacterial and anti-inflammatory effects but also helps regulate lipid production. It is well-distributed and retained in the eyelids, enhancing its therapeutic potential [10,11]. While numerous studies have investigated the use of topical azithromycin for posterior blepharitis, its effects on various parameters—such as lipid layer quality and quantity, tear film stability, lid margin abnormalities, meibomian gland morphology, tear osmolarity, and ocular symptoms—remain insufficiently explored [12, 13].

 

Tetracyclines are among the earliest broad-spectrum antibiotics that are well-tolerated and easy to administer. They are effective against a wide range of diseases, including plague, cholera, typhoid, syphilis, Legionnaire’s disease, and anthrax. Additionally, some tetracyclines are used to treat conditions such as malaria, Lyme disease, tuberculosis, Rocky Mountain spotted fever, and leprosy. Evidence suggests humans first encountered tetracyclines unintentionally in ancient times, as bone samples over 1,500 years old have revealed traces of these compounds.

Following World War II, tetracyclines were "rediscovered" during an intensive search for new antibiotics at Lederle Laboratories and Pfizer. Their bacteriostatic effect stems from the inhibition of protein biosynthesis. Since the structural elucidation by Robert Woodward, Lloyd Hillyard Conover, and others in the 1950s, tetracyclines have become a significant focus of natural product synthesis research.

 

This study aimed to comprehensively evaluate the efficacy of azithromycin and tetracycline eyedrops with Meibomitis-Related Keratoconjunctivitis (MRKC), considering a broad range of clinical outcomes.

MATERIALS AND METHODS

The study was conducted in the Outpatient Department of Ophthalmology at a tertiary care hospital over a one year, in the year of 2017, following approval from the institutional ethics committee. Written informed consent was obtained from patients or their attendants. patients under inclusion criteria, they were divided into two groups and named as group A & B. Group a patients were treated with Azithromycin, group B patients were treated with tetracycline respectively. Data collected included patients' sociodemographic details, symptoms, MRKC subtypes, conjunctival hyperemia grade, bulbar conjunctivitis and the percentage of conjunctival vascular curvature. These parameters were recorded at baseline and monitored weekly for five weeks during treatment.

 

Inclusion Criteria

  1. Patients aged 20–40 years attending the ophthalmology OPD.
  2. Patients able to follow-up schedule.
  3. Patients or their attendants willing to provide informed consent.
  4. Patients with financial support to purchase required medications.
  5. Patients not using any ocular drugs at the time of enrolment.

 

Exclusion Criteria

  1. Patients younger than 20 years of age.
  2. Patients wearing contact lenses during the study period.
  3. Patients with any ocular disorders.
  4. Patients with a history of ocular surgery within the last one months.
  5. Patients or their attendants unwilling to provide informed consent.

 

Study Design

Participants were randomly divided into three groups using the chit method:

  • Group A: Patients treated with Azithromycin  
  • Group B: Patients treated with Tetracycline

 

Statistical Analysis

Data collected during the study were recorded in Microsoft Excel and analysed using SPSS software (version 16). An unpaired t-test was conducted to compare the two groups. A p-value of less than 0.05 was considered statistically significant, while a p-value of less than 0.005 was deemed highly significant.

 

RESULTS

The per the present study majority of the patients were male 55.32 % followed by female 44.67% (Table 01). Table 02 As per the age group of the patients majority of the patients were under the age group of 31 to 35 years 92 (46.70%) patients followed by 36 to 40 years 81 (46.19%).  respectively.

 

Table 01 Gender distribution among meibomitis associated keratoconjunctivitis patients.

Gender

No of Patients

Percentage no of patients

Male

109

55.32

Female

88

44.67

Total no of patients

197

100.00

 

Table 02 Age group distribution among meibomitis associated keratoconjunctivitis patients.

Age groups

No of patients

Percentage no of patients

20 to 25 Years

21

10.82

26 to 30 Years

66

33.50

31 to 35 Years

92

46.70

36 to 40 Years

81

46.19

Total No of Patients

197

100.00

 

Table 03: effect of Meibomitis related keratoconjunctivitis in different eyes;

Keratoconjunctivitis

No of patients

Percentage no of patients

Single Eye

61

46.19

Both Eye’s

136

69.03

Total No of patients

197

100.00

 

Table 04 Bulbar Conjunctivitis in meibomitis associate keratoconjunctivitis patients.

Bulbar Conjunctivitis

No of Patients

Percentage no of patients

Severe Vasodilation

13

6.59

Moderate Vasodilation

62

31.47

Mild Vasodilation

113

57.36

No Vasodilation

09

4.56

Total No Patients

197

100.00

 

Table 05 Type of meibomitis related keratoconjunctivitis patients.

Types of MRKC

No of patients

Percentage no of patients

Phlyctenular

146

74.11

Non phlyctenular

51

25.88

Total No of Patients

197

100.00

 

Table 06: Number of patients had conjunctival hyperemia in meibomitis keratoconjunctivitis patients.

Conjunctival Hyperemia

No of patients

Percentage no of patients

Present

181

91.87

Absent

16

08.12

Total No of patients

197

100.00

 

Table 07 Symptoms of conjunctival hyperemia in meibomitis keratoconjunctivitis patients.  146

Symptoms

No of patients (197)

Percentage no of patients

Itchy eyes

112

56.85.

Watery eyes

129

65.48

Sensitivity to light

95

48.22

Redness of Eyes

138

70.05

Swelling of eyelids margin

71

36.05

Swelling of palpebral conjunctiva

75

38.07

Superficial vascularization

31

15.73

granulomatous nodules in the cornea

48

24.36

Conjunctival hyperemia

197

100.00

Blurry vision

114

57.86

Total No of Patients

197

 

 

Table 08 number of patients observed with Conjunctival hyperemia in meibomitis keratoconjunctivitis patients.

 

Group A (98)

Group B (99)

Visits conducted after drug administration

No of Patients

Percentage

No of patients

Percentage

1st Visit

(1st day of visit)

91

100.00

90

100.00

2nd Visit

(1st Week)

83

91.20

79

87.77

3rd Visit

(2nd Week)

65

71.42

57

63.33

4th Visit

(3rd Week)

43

47.25

34

37.77

5th Visit

(4th Week)

19

20.83

13

14.44

DISCUSSION

The present study was conducted with approval from the institutional ethics committee, and informed consent was obtained from all participating patients. The study population consisted of a majority of male patients (109; 55.32%) compared to females (88; 44.67%) (Table 1). The largest age group was 31–35 years, comprising 92 patients (46.70%), followed by 36–40 years (81; 41.19%), 26–30 years (66; 33.50%), and 20–25 years (21; 10.82%) (Table 2).

 

Keratoconjunctivitis is defined as inflammation of the eyes, affecting either one or both. In this study, most patients (136; 69.03%) presented with keratoconjunctivitis in both eyes, while 61 patients (30.97%) had it in a single eye (Table 3). Bulbar conjunctivitis associated with meibomitis-related keratoconjunctivitis is caused by vasodilation of the eye's blood vessels. Mild vasodilation was the most common finding (113; 57.36%), followed by moderate (62; 31.47%), severe (13; 6.59%), and no vasodilation (9; 4.56%) (Table 4).

 

Meibomitis-related keratoconjunctivitis can manifest as either phlyctenular or non-phlyctenular types. In this study, the majority of patients had the phlyctenular type (146; 74.11%), while 51 patients (25.88%) presented with the non-phlyctenular type (Table 5).

 

The presence or absence of conjunctival hyperemia is a significant factor in the development of keratoconjunctivitis. Most patients (181; 91.87%) exhibited conjunctival hyperemia, while it was absent in 16 patients (8.12%) (Table 6).

 

Symptoms associated with meibomitis-related keratoconjunctivitis were assessed in 197 patients. Conjunctival hyperemia was present in all patients (197; 100.00%), followed by redness of the eyes (138; 70.05%), watery eyes (129; 65.48%), blurry vision (114; 56.86%), itchy eyes (112; 56.85%), sensitivity to light (95; 48.22%), swelling of the palpebral conjunctiva (75; 38.07%), eyelid margin swelling (71; 36.05%), granulomatous nodules in the cornea (48; 24.36%), and superficial vascularization (31; 15.73%) (Table 7).

 

Conjunctival hyperemia was monitored across both treatment groups (A and B) over multiple visits. At the first visit, groups A and B included 91 and 90 patients, respectively. After the first week of treatment (second visit), hyperemia was reduced to 83 patients (91.20%) in group A and 79 patients (87.77%) in group B. By the second week (third visit), further reductions were observed: 65 patients (71.42%) in group A and 57 patients (63.33%) in group B. At the third week (fourth visit), 43 patients (47.25%) remained affected in group A and 34 (37.77%) in group B. By the fourth week (fifth visit), conjunctival hyperemia was reduced to 19 patients (20.83%) in group A and 13 (14.44%) in group B. These results indicate that group A demonstrated a greater reduction in keratoconjunctivitis symptoms compared to group B (Table 8).

According to Takashi Suzuki (2016) [14], all eyes with phlyctenular keratitis exhibited corneal nodules, neovascularization, and superficial punctate keratopathy, findings absent in normal controls. The mean meiboscore of phlyctenular keratitis patients (upper lid: 2.9 ± 0.3, lower lid: 2.7 ± 0.5) was significantly higher compared to controls (upper lid: 0.4 ± 0.6, lower lid: 0.1 ± 0.3). Noncontact meibography revealed meibomian gland loss in phlyctenular keratitis patients, highlighting a potential link between meibomian gland abnormalities in young individuals and the development of phlyctenular keratitis.

CONCLUSION

Azithromycin, a macrolide antibiotic, is highly effective in eliminating a wide range of bacteria. According to the study, azithromycin demonstrated greater improvement in treating keratoconjunctivitis compared to tetracycline.

REFERENCES
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  2. Arita R, Mizoguchi T, Kawashima M, et al. Meibomian gland dysfunction and dry eye are similar, but different based on a population-based study (Hirado-Takushima study) in Japan. Am J Ophthalmol 2019;207:410–418.
  3. Nelson JD, Shimazaki J, Benitez-del-Castillo JM, et al. The international workshop on meibomian gland dysfunction: Report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci 2011;52:1930–1937
  4. Knop E, Knop N, Millar T, et al. The international workshop on meibomian gland dysfunction: Report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci 2011;52:1938–1978.
  5. Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: Executive summary. Invest Ophthalmol Vis  Sci 2011;52:1922–1929.
  6. Geerling G, Tauber J, Baudouin C, et al. The international workshop on meibomian gland dysfunction: Report of the subcommittee on management and treatment of meibomian gland dysfunction. Invest Ophthalmol Vis Sci2011;52:2050–2064.
  7. Liu Y, Kam WR, Ding J, et al. One man’s poison is another man’s meat: Using azithromycin-induced phospholipidosis to promote ocular surface health. Toxicology 2014;320:1–5.
  8. Liu Y, Kam WR,Ding J, et al. Effect of azithromycin on lipid accumulation in immortalized human meibomian gland epithelial cells. JAMA Ophthalmol 2014;132:226–228.
  9. Thode AR, Latkany RA. Current and emerging therapeutic strategies for the treatment of meibomian gland dysfunction (MGD). Drugs 2015;75:11771185.
  10. Akpek EK, Vittitow J, Verhoeven RS, et al. Ocular surface distribution and pharmacokinetics of a novel ophthalmic 1% azithromycin formulation. JOcul Pharmacol Ther 2009;25:433–439.
  11. Luchs J. Efficacy of topical azithromycin ophthalmic solution 1% in the treatment of posterior blepharitis. Adv Ther 2008;25:858–870.
  12. Foulks GN, Borchman D, Yappert M, et al. Topical azithromycin therapy for meibomian gland dysfunction: Clinical response and lipid alterations. Cornea 2010;29:781–788.
  13. Haque RM, Torkildsen GL, Brubaker K, et al. Multicenter open-label study evaluating the efficacy of azithromycin ophthalmic solution 1% on the signs and symptoms of subjects with blepharitis. Cornea 2010; 29:871–877.
  14. Takashi Suzuki, Naoyuki Morishige, et al. Morphological changes in the meibomian glands of patients with phlyctenular keratitis: a multicenter cross-sectional study. BMC Ophthalmology. 2016;16:178.

 

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