|Year : 1999 | Volume
| Issue : 2 | Page : 121-124
Indiscriminate use of topical antibiotics: A menace
Arun Kumar Sood, Alka Gupta, Tulika Dabral
Upgraded Department of Ophthalmology, L.L.R.M. Medical College, Meerut, India
Arun Kumar Sood
Department of Ophthalmology, L.L.R.M. Medical College, Meerut - 250 004
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Sood AK, Gupta A, Dabral T. Indiscriminate use of topical antibiotics: A menace. Indian J Ophthalmol 1999;47:121-4
Indiscriminate use of topical antibiotics causes histological and ultrastructural changes in conjunctiva leading to decreased tear break-up time and dry eye state.
Lids, tears, mucous and epithelial surfaces interact to produce a complex physiochemical system that ensures optimal health of cornea. Conjunctival xerosis may cause imbalance of this system, resulting in changes which are incompatible with corneal clarity and normal eyesight. Increasing evidence indicates that long-term usage of topically administered medications can induce changes in the conjunctiva and ocular surface. Although clinicians view the conjunctiva as a passive, semipermeable barrier that allows drugs to enter the eye, it is nevertheless a living dynamic tissue that can respond to stress with inflammation, scarring, keratinization, and neovascularization.
The normal conjunctiva consists of two layers, the epithelium and substantia propria. The epithelium comprises non-keratinised stratified squamous cells which are 5-6 layers in thickness. With chronic exposure and drying, the epithelium may become keratinised. The stroma (substantia propria) consists of richly vascularised connective tissue which is separated from the epithelium by a basement membrane. The goblet cells are located within the epithelium and secrete the innermost mucinous portion of the tear film. There is a regional variation in the distribution and density per unit area of goblet cells, averaging 8.84 ± 4.66 cells/mm, their density reduced in dry eye and increased in chronic inflammatory conditions.
This study focuses on commonly prescribed and sometimes indiscriminately used topical medications like antibiotic drops. Our aim was to evaluate the long-term effects of various preparations of antibiotics on the conjunctiva by studying their histopathological details and comparing them with the clinical signs and symptoms of dry eye in the respective groups.
| Materials and Methods|| |
Forty patients attending the outpatient department of Ophthalmology, Medical College, Meerut, U.P., India were asked to provide a detailed history of usage of previous topical therapy and the duration of their usage along with any complaints suggestive of dry eye. Patients also underwent a complete ophthalmic examination, to eliminate any cause of dry eye such as cicatricial pemphigoid, Sjogren's syndrome, Keratitis sicca, and Steven Johnson syndrome. Schirmer's test and tear break-up time were performed on each eye. The patients were divided into two groups of 20 patients each. Group A included normal (control) healthy population 40-60 years of age with no history of previous usage of topical drug; and Group B included patients on topical antibiotic therapy for more than 6 months. Antibiotics like ciprofloxacin, chloromphenicol and sulphacetamide were used in the post-operative period, or for conjunctivitis, keratitis or lid infections. Once these antibiotics were prescribed for some ailments, the patients continued to use them for years even after being relieved of the symptoms.
| Conjunctival biopsy|| |
Conjunctival specimens measuring 3x3 mm were obtained from the inferonasal bulbar conjunctiva after applying of 4% xylocain tampons for 2 minutes. The site was chosen because the inferonasal region has the maximum density of goblet cells. The study of histopathological changes would therefore be more distinct in comparison to the normal control group in this region. Also, the bulbar conjunctiva being loosely adherent is easier and safer to remove in comparison to the palpebral conjunctiva where the density of goblet cells is known to be the lowest.
The conjunctival specimens were immediately fixed in 10% neutral buffered formalin, processed and stained with Haematoxylin & Eosin and Toluidine blue for mast cells. Light microscopic analysis of specimens was performed with the x100/oil immersion objective of a standard light microscope and x10 eye piece fitted with an indexed square grating graticule. For each specimen, the number of goblet cells and thickness of epithelial layer were estimated in the epithelial layer and were counted in the conjunctival substantia propria. With all the specimens, a count was made in the epithelium and substantia propria in five field areas, each field comprising 0.4mm2 area of a square graticule. Thus cell counts were quantified in a 0.2 mm2 area representing one section (= one square area).
| Electron Microscopy|| |
Specimens for electron microscopic study were fixed in formal gluteraldehyde and then processed for the ultrastructural study of the specimens.
| Statistical analysis || |
The student t-test (unpaired) was applied to test the significance of difference between two means.
| Results|| |
The number of cases in each group with their age and sex distribution, the average duration of exposure of usage of topical antibiotics and the results of Schirmir's test and tear break-up time are tabulated in [Table - 1].
[Table - 2] shows the histopathological details of the conjunctival specimens of the patients in Groups A and B [Figure - 1] [Figure - 2].
The mean average results of Schirmer's test revealed no statistically significant difference in the two groups under study. The results of tear break-up time showed a highly significant (p < 0.001) decrease in the antibiotic group as compared to normal.
During a mean exposure time of 11.5 ± 5.18 months of topical antibiotic drops a statistically significant decrease in goblet cell count, with an overall increase in mean cellularity occurred in the conjunctiva of patients in comparison to the normal control group. Thus relative to Group A, Group B contained significantly fewer goblet cells (21.2 ± 2.55 vs 9.9 ± 4.28, p < 0.001), and highly significantly greater epithelial thickness (7.09 ± 0.81 vs 11.75 ± 9.0 p < 0.001), fibroblasts (59.4 ± 11.83 vs 103.33 ± 26.57, p < 0.001),lymphocytes (14.9 ± 5.3 vs 69.17 ± 30.8, p < 0.001), and significantly more polymorphonuclear cells (0 vs 17.83 ± 14.4, p< 0.05), macrophages (10.1 ± 2.02 vs 14.8 ± 8.45, p < 0.05), mast cells (4.6 ± 2.56 vs 12.12 ± 5.69, p < 0.05), and plasma cells (0 vs 8.17 ± 6.48, p < 0.05).
| Electron microscopy|| |
A) Normal conjunctiva: Electron microscopy revealed regularly arranged epithelial cells with no loosening and destruction of cells, with a thickness of 6-7 layers of epithelium. Goblet cell count was 2-3 goblet cells / low power field and secretory vesicles were found in the ultrastructre of goblet cell [Figures:3][Figure - 4]. Surface epithelium showed microvilli projections. Tight junctions were compact. Basal cells showed melanin deposits. Collagen bundles were present in groups.
B) Conjunctiva of antibiotic users: Epithelial thickness was increased. Flattening of surface microvilli was observed with a reduced number of goblet cells. Keratinocytes showed vacuolation and increase in collagen in basal layer [Figure - 5][Figure - 6].
| Discussion|| |
Treatment with topical drug includes not only the active agent but a vehicle, the preservative and the pH of the solution. It was not the aim of study to determine which specific component of the therapy had an effect on the conjunctiva, but to determine the effect of the therapeutic regimens to which patients are exposed in clinical practice.
Usage of antibiotic drops clearly correlated with dry eye and decreased tear break-up-time and compared well with the histopathological changes., A reduced tear break-up time shows a disturbance in the formation of tear film, that is explained by decrease in mucin layer due to a reduced goblet cell count. An increase in chronic and acute inflammatory cells points to an increased fibroblastic activity, indicated by the scarring of the conjunctiva., These findings were substantiated by electron microscopic changes which also revealed features of dry eye with flattened surface microvilli, decreased goblet cell count and increased collgenization.
A mean exposure period of 11.5 ± 5.18 months can thus lead to significant changes in the conjunctiva Hence, the long-term usage of antibiotic drops should be restricted. Judicious prescription and proper patient education can prevent the harm caused by these topical medications. Topical antibiotics drug induced dry eye is preventable; with indiscriminate use it could become chronic and plague its victim for the duration of their lives if timely precautions are not taken.
This is a preliminary study which indicates further study on a larger population and isolation of specific causative agent amongst the ingredients in commercial preparations that initiates the conjunctival changes.
| References|| |
Robert RA. Conjunctival goblet cell density in normal subjects and in dry eye syndromes. Invest Ophthalmol
Derous D, Wole Keizer RJ, Wolf Rouendaal DDE. Conjunctival keratinization, an abnormal reaction to an ocular beta blocker. Acta Ophthalmologica
Broadway DC, Grierson IL, O'Brien C, Hitchings RA. Adverse effects of topical antiglaucoma medication. The conjunctival cell profile. Arch Ophthalmol
Broadway DC, Grierson IL, O'Brien C, Hitchings RA. Adverse effect of topical antiglaucoma medication. The outcome of filtering surgery. Arch Ohthalmol
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6]
[Table - 1], [Table - 2]