{'fraction_non_alphanumeric': 0.024931756141947224, 'fraction_numerical': 0.012374886260236579, 'mean_word_length': 4.954496208017335, 'pattern_counts': {'":': 0, '<': 1, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
A comparative study of benzalkonium chloride-free latanoprost versus benzalkonium chloride-preserved latanoprost on ocular surface health in patients of primary open angle glaucoma

Glaucoma, a vision debilitating disorder has become the second leading cause of blindness worldwide. Topical medications are the crux of anti-glaucoma therapy. Preservatives form an essential ingredient of these topical medications as they prevent microbial contamination and maintain their efficacy. Benzalkonium chloride (BKC) is reigning the ophthalmic industry since 1940s bagging the tag of most commonly used preservative. However the long-term use of BKC has been found to be hazardous. It has dose-dependent effects. It damages the tear film and activates the production of inflammatory mediators. The main purpose of our study was to compare the effect of BKC-free latanoprost versus BKC-preserved latanoprost on ocular surface health in patients of primary open angle glaucoma (POAG) by means of parameters like Schirmer test, Tear film break up time (TBUT) and ocular surface disease index (OSDI) questionnaire.

After obtaining approval from Institutional Ethics Committee (IEC), patient recruitment was started. Written informed consent was taken from all patients. Thirty established cases of POAG who were already on BKC-preserved latanoprost for atleast more than three months were enrolled. Their chief complaints, medical history and past ocular history were taken. Patients with past history of any ocular surgery in last one year, intake of any medication causing dry eye, patients suffering from rheumatoid arthritis, scleroderma or any other disease where dry eye is one of the manifestations, history of any ocular trauma in last three months, concomitant conjunctivitis, keratitis or uveitis and patients using contact lens during the study time period were excluded. Schirmer test was performed by using Schirmer tear test strips. Strip was carefully removed and kept in the lateral part of lower conjunctival sac of patients for about five minutes and then the length of the wet area was recorded. Schirmer test reading more than 10 mm was considered to be normal. 9 For Tear film break up time, diagnostic ophthalmic sterilized fluorescein sodium strips were used. Strip was moistened with sterile ophthalmic solution or saline and its tip was placed on bulbar cornea. After the tear film took a uniform fluorescent green appearance, patient was instructed not to blink for the next 60 seconds. Time between one complete blink and appearance of first dark spot was taken as TBUT. TBUT reading more than 10 seconds was taken to be normal. 9 Patients were required to answer an OSDI questionnaire which is basically a "12-item" questionnaire based on ocular complaints of the patient in the past one week. OSDI score ranges from 0 to 100. OSDI score ≤12 was taken to be normal. 10 After performing Schirmer test, Tear film break up time and calculation of OSDI score, patients were switched over to BKC-free latanoprost for another three months. At 6 and 12 weeks of follow-up, Schirmer test, Tear film break up time and calculation of OSDI score were performed again.
Statistical analysis was performed using SPSS software version 20.0 Chicago, Illinois, USA. For analysis of quantitative data, paired t test was used. For categorical variables and qualitative data, chi square test was used. The results were finally presented in tables, charts and bar diagrams. p value less than 0.05 was considered as significant (S) and less than 0.01 was considered as highly significant (HS).

RESULTS
A total of thirty POAG subjects who were on BKCpreserved latanoprost for atleast more than three months were enrolled at the baseline and then they were switched over to BKC-free latanoprost for another three months. Maximum number of patients were in the age group of 61-70 years. The mean age of presentation was 66.9±10.56 years. A male preponderance in glaucoma patients was seen in the study (n=23; 76.67%).

DISCUSSION
Since long-term use of BKC has been implicated in causing OSD in glaucoma patients, the purpose of the present study was to compare the effect of Benzalkonium
On comparison of frequency of symptoms reported by patients on BKC-preserved latanoprost at baseline and 12 weeks after starting treatment with BKC-free latanoprost, a decrease in the frequency was reported at 12 weeks. Statistically significant changes were observed for every symptom (p<0.05) except frequent blinking (p=0.291). Improvement in the frequency of symptoms with preservative free medication in glaucoma patients has also been reported by Pisella et al, Jaenen et al and Uusitalo et al. [18][19][20] Results of the present study were in accordance with the results of previously conducted studies.
The study has its own limitations accounting to its openlabel design, lesser number of patients and shorter duration of follow-up.

CONCLUSION
In a nutshell, the study concludes that BKC-free medications are indeed healthy for the ocular surface of glaucoma patients on long-term therapy as compared to BKC-preserved medications. BKC-preserved therapy deranges the tear film status of glaucoma patients and hampers their adherence to the treatment. It is therefore necessary to explore alternatives to BKC. Single Dose Units (SDUs) is an emerging option which has been launched already, however more horizons of research and development are required in the field of ophthalmic preservative industry.