Comparison of Efficacy and Safety of Ripasudil 0.4% and Bimatoprost 0.01% in Patients of Primary Open Angle Glaucoma and Ocular Hypertension

: Objective: To compare Mean Intraocular pressure reduction produced POAG and OHT patients, classified according to their baseline Intraocular pressure (Group A with baseline Intraocular pressure between 22-25mmHg, Group B with baseline Intraocular pressure between 26-30mmHg), at last follow-up visit at 3 months. Study Design and Type: Prospective double blind randomized control trial study. Methodology: IOP measurement with a Calibrated Goldmann Applanation Tonometer (GAT) was done, with Diurnal variation recording at 8am, 12.00 and 4pm as baseline, and then at 2 weeks, 6 weeks and 3months. Two consecutive measurements of IOP in each eye were obtained at each time point and average of the two was taken as the IOP. If the 2 measurements differ by >2mmHg, a 3 rd measurement was obtained and the middle value of the 3 recordings was taken as the IOP. The data analysis and patient examination took place between February 2021 to till February 2022. Results: Distributions of patients of primary open angle glaucoma and Ocular hypertension into Base line IOP 22-25mmhg (group 1) and Base line IOP 26-30mmhg (group 2). . Total 35 patients were included in this study one was lost to follow up and hence data analysis was done


Methodology:
The study followed the guidelines contained in the declaration of Helsinki and approval was taken from the institutional Review Board. Informed written consent was taken in each case regarding the purpose of the study and also for publication of data thereafter. It is a Tertiary Eye care hospital based "Interventional randomized parallel group study" This study was conducted from (February 2021 till February 2022).

STUDY DESIGN:
Prospective double blind randomized control trial study.

INCLUSION CRITERIA:
• All newly diagnosed patient of primary open angle glaucoma and ocular hypertension with IOP between 22-30mmHg were included in the study. • Eligible patients were screened for inclusion and exclusion criteria and were randomly assigned to each group in a 1:1 ratio. • 40 years of age or older.
• POAG or OHT in both eyes (POAG in one eye and OHT in the fellow eye is acceptable). • Complete slit lamp examination with documentation of any pre-existing signs and or symptoms at baseline • IOP measurement with a Calibrated Goldmann Applanation Tonometer (GAT) was done, with Diurnal variation recording at 8am, 12.00 and 4pm as baseline, and then at 2 weeks, 6 weeks and 3months. Two consecutive measurements of IOP in each eye were obtained at each time point and average of the two was taken as the IOP. If the 2 measurements differ by >2mmHg, a 3 rd measurement was obtained and the middle value of the 3 recordings was taken as the IOP. • For randomization into study groups, individuals were required to have an un-medicated IOP between 22 to 30 mmHg at baseline visit. Patients were instructed to in still the medication daily in both eyes at 9 PM. No other ocular medication except preservative free lubricants, were allowed during study period.
To study the effect of baseline IOP on the IOP lowering efficacy of the two drugs, patients were segregated into two groups, according to their baseline IOP as follows-Group 1: Base line IOP 22-25mmHg. Group 2: Base line IOP 26-30mmHg.
Randomization method: As the study groups were formed for IOP lowering efficacy of Bimatoprost and Netarsudil drugs, the randomization was done for Bimatoprost and Netarsudil group. Initially patients were enrolled based on baseline IOP measurements resulting in lower IOP (22-25 mmHg) and higher IOP (26-30 mm Hg) group, consequently each participant of both the groups were given Bimatoprost and Netarsudil on alternate basis resulting in two study group formation at the baseline consisting of 17 patients who were given either Bimatoprost or Netarsudil in each study group (Bimatoprost group and Ripasudil group). The randomization was done by alternate allocation of both the drugs to the participants in each group of the study without any selection bias. All patients had undergone a random 1:1 allocation in Netarsudil and Bimatoprost Groups, irrespective of their baseline IOPs.
Analyzing this information gave us an idea about how the IOP decreasing efficacy of Ripasudil 0.4% and Bimatoprost 0.01% is correlated with the baseline IOP. All patients had undergone Gonioscopy and (CCT) central corneal thickness assessment at baseline visits. HFA 24-2 and disc photography were done at base line visit. SS-OCT for RNFL, ONH, GCC Informed consent: before study the study will be discussed with each subject. Subjects wishing to participate must give written informed consent. Conflict of Interest: there are no financial conflicts of interest to disclose.  Table 1 and Figure 1. Out of 34, total 23 (67.65%) patients were included in group 1 and 11 (32.35%) patients were included in group 2.  Table 2 and Figure 2. Values are expressed as mean, median, ±SD, minimum and maximum. Range of age was 42 to 65 years in group 1 and 33 to 64 years in group 2. The mean age was 58.30±6.98 in group 1 and 55.29±8.03 in group 2. The mean age was not significantly different in between groups.  Table 4: Comparisons of drug use in group 1 and group 2 Table 4 and Figure 8 show the comparisons of drug use in group 1 and group 2. The percentage of number of patients used Bimatoprost and Netarsudil drug were 52.17% and 47.83% in group 1 and 45.45% and 54.55% in group 2, respectively. The percentage of number of patients used Bimatoprost and Ripasudil drug were not significantly different in between groups.  Table 5 shows the correlation in between grading with IOP at baseline to 3 months follow-up in overall patients. The grading was not significantly correlated with change in IOP at baseline, 2 weeks, 6 weeks and 3 months. In this study the bimatoprost and netarsudil drugs were significantly reduced the IOP from baseline to 3 months follow-up in both the groups. Numerous prior observational studies have shown that bimatoprost 0.01% is well tolerated and effective at lowering IOP.

Group 1 (n=23)
[60] Patients with POAG or OHT who had never received treatment benefited from an IOP reduction of 30% over the course of 12 weeks in a clinical practise setting, with 93% of patients suffering mild, trace, or no hyperaemia. [18] In patients who switched from prior medication, bimatoprost 0.01% was well tolerated and related with an additional 10%-15% reduction in IOP. [25] In a comprehensive observational trial with more than 10,000 patients, bimatoprost 0.01% significantly reduced mean IOP from a baseline of 20.1-4.5 mmHg in all study participants and from 20.1-6.5 mmHg in patients who had not previously received treatment.
[46] bimatoprost 0.01% is equal to bimatoprost 0.03% in terms of effectiveness for decreasing IOP throughout a 12-month treatment period, according to research by Katz et al. [44] bimatoprost 0.01% demonstrated better patient adherence than bimatoprost 0.03% in prior observational research.
[72] Adherence in the current study was better than or equal to that of the previous therapy in more than 97% of patients who switched from a previous therapy to bimatoprost 0.01%. The mean IOP for the treatment group changed by around 20% as a result of Netarsudil treatment. While tests on normotensive monkeys revealed a significantly bigger increase, 53% at 6 hours after a single injection, the degree of the impact appears to vary by species. Animal studies also demonstrated an increase in outflow facility with Netarsudil therapy. [31] However, the Netarsudil concentration in that trial was higher (0.04% vs. 0.02% in our investigation), and two drops rather than one were administered to each eye. In this study both bimatoprost and netarsudil showed significant decrease in IOP, however, bimatoprost was found to be more effective in decreasing IOP in all patients as compared to netarsudil especially more in higher base line group.