This was a prospective study conducted after getting the ethical clearance from the Institutional Ethics Committee (IEC), and the data were collected by strictly adhering to the inclusion and exclusion criteria. Patients of both the genders, who were diagnosed with primary open-angle glaucoma with an age of above 18 years, were included in this study. Exclusion criteria involves pregnant women, nursing women, women who were planning to conceive and who were using adequate birth control measures, subjects with chronic/recurrent inflammatory eye diseases, and patients with drug-induced glaucoma [13].
The diagnosis of POAG is based on the IOP measured by using the Goldmann applanation tonometer and also by analyzing the visual field defects. The other criteria in the diagnosis includes glaucomatous disc with the presence of focal or diffuse optic disc rim with or without any defects in the layers of retinal nerve fibers. The central corneal thickness in these patients was measured by using a pachymeter.
Measurement of the intraocular pressure by the Goldmann applanation tonometer
The thicker cornea shows a higher IOP than it actually exists which indicates the risk of developing glaucoma. The diagnosis of glaucoma is made after conducting a comprehensive eye examination. Initially, the optic nerve examination is done by using the stereo biomicroscopic slit lamp. It measures the cup-to-disc ratio and disc rim integrity as the glaucoma patients usually have higher cup–disc ratio [14,15,16,17,18]. Further, the intraocular pressure is measured using Goldmann applanation tonometry which is considered as the golden standard for the measurement of IOP. However, Goldmann applanation tonometry is dependent on corneal rigidity, curvature, thickness, and other biochemical properties. So, there is a high probability for error in patients with atypical corneas (or) other ocular conditions [19].
Initially, the prism was disinfected with isopropyl alcohol 70% and was cleaned by using sterile water. Further, it was wiped with a clean dry swab (as the residue of disinfectant may cause a caustic burn on the cornea). The graduation is marked at “0” on the prism which is present in white color on the tonometer head, and the calibrated dial was set to 10 mmHg on the tonometer. The patient was asked to sit comfortably at an appropriate height by properly resting their chin on the chin rest, and the forehead should be placed against the head band of the slit lamp. The magnification of the slit lamp was set to 10×.
Procedure
The IOP was measured after the administration of the local anesthetic drops in order to block the transmission of pain signals, and the fluorescein strips were used to stain the eyes. The beam of the slit on tonometer was adjusted towards the right side of the patient during the IOP measurement of the right eye, while it can be adjusted to the left-hand side of the patient during the IOP measurement of the left eye. Blue and green filters are moved to produce the coloured beam. The beam produced was bright making the fluorescein rings more visible. After fixing the gaze, the patient was asked to look straight with eyes opened widely. By using the thumb, the patient’s eyelid must be held gently without applying much pressure on the eye. The blue light from the slit lamp was directed towards the prism ensuring that the head is perpendicular to the eye. The tonometer was slowly moved forward until the prism rests at the centre of the cornea. Using the other hand, the calibrated dial on the tonometer was turned clockwise until the two fluorescein circles in the prism were observed to meet forming a horizontal “S” shape. The readings on the dial were recorded after withdrawing the prism from the corneal surface. The same procedure was repeated for the other eye after wiping the prism with a disinfectant swab [20].
Measurement of the central corneal thickness by using the pachymeter
Few studies suggested that applanation pressures vary significantly depending on the corneal thickness as some of the patients diagnosed with ocular hypertension actually maybe normotensive but corrected for increased corneal thickness. Thus, along with the intraocular pressure measurement, the corneal thickness was also measured in order to make accurate interpretations in the process of diagnosis [19]. Corneal thickness serves the need to measure the pressure in the eyes as it masks the accurate readings of the eye pressure, leading to misinterpretation. A pachymeter is a simple, painless test to measure the central corneal thickness. The normal range of corneal thickness is 540–560 μm. Patients with a thin cornea usually show low IOP readings. It becomes a threat if the IOP reading obtained is higher than the actual reading, which states the risk of developing glaucoma leading to loss of vision if left untreated. Patients with thicker cornea show higher IOP than the suspected readings thus lowering the risk of developing glaucoma [21].
Procedure
After administering a drop of 0.5% proparacaine anesthetic into the affected eye, the patient was asked to look straight without blinking. An ultrasound probe tip was gently placed at the center of the cornea perpendicular to the posterior surface of the eye. The ultrasound rays were passed through the cornea via a probe that receives the echoes from the cornea and displays the readings of central corneal thickness [22,23,24].
Fixed drug combinations prescribed to the study subjects
The patients who were diagnosed with POAG were categorized into two groups. Patients who were not contraindicated with β-adrenoceptor antagonist were categorized into Group A, while the patients who were contraindicated with β-adrenoceptor antagonist were categorized into Group B.
Group A subjects were prescribed with brinzolamide 1%/timolol maleate 0.5% ophthalmic suspension which is a combination of carbonic anhydrase inhibitor and β-adrenoceptor antagonist. This combination (BTFC) was used to reduce the elevated intraocular pressure primarily by reducing aqueous humor secretion by different mechanisms of action. Brinzolamide acts by decreasing the production of the clear fluid inside the eye and timolol works by reducing the production of aqueous humor in the ciliary epithelium. The combined effect of these two substances is highly effective than either substance used alone [25]. This ophthalmic suspension was administered by the patients as one drop twice daily into the affected eye(s). Group B subjects were prescribed with brinzolamide 1%/brimonidine tartarate 0.2% ophthalmic suspension which is a combination of carbonic anhydrase inhibitor and α2-adrenergic agonist. This combination (BBFC) is of two proven drugs into a single dosage form. Brimonidine also decreases the fluid production along with the benefit that increases the fluid outflow [26]. This ophthalmic suspension was administered by the patients as one drop three times a day into the affected eye(s). To compare the efficacy of these two fixed drug combinations, the IOP and the corneal thickness were measured at baseline followed by 4th-week, 8th-week, and 12th-week follow-ups.
Statistical analysis
The data were analyzed by using the statistical software Statistical Package for Social Sciences (SPSS version 21.0). Mean and standard deviations were calculated, and t test was performed in order to obtain the p values at 95% confidence interval (p ≤ 0.05). The statistically significant values were denoted with an asterisk (*).