Effect on contrast sensitivity and ocular surface with different formulations of preservative free topical Travoprost in treatment naive Primary open angle glaucoma patients

Glaucoma encompasses a range of progressive optic nerve disorders causing retinal ganglion cell (RGC) loss, optic neuropathy with corresponding visual field defects, potentially leading to permanent blindness. Loss of RGCs is linked to the elevation of intraocular pressure (IOP).1 Without IOP reduction treatment, glaucomatous damage can advance from mild field damage to unilateral blindness in approximately 23 years, while treatment extends this progression to about 35 years.2 As the primary cause of irreversible blindness worldwide, glaucoma emerges as a significant public health issue demanding attention and effective interventions. The United Nations‟ population projections estimates that over 111.8 million will suffer from glaucoma by 2040.3, 4 Globally, primary open-angle glaucoma (POAG) is the most prevalent form of glaucoma.5 Based on available data, an estimated 11.2 million individuals aged over 40 years in India are believed to have glaucoma, underscoring the significant prevalence of the condition in the country, and POAG affects 6.48 million persons.6 To make matters worse, the visual compromise results not just from the disease but also its treatment. High IOP significantly increases the risk of POAG.7 Uncontrolled POAG and resultant glaucomatous optic neuropathy (GON) results in irreversible damage to the visual function.8 In some individuals, a reduction in intraocular pressure may lead to partial improvement in visual field defects.8 In the natural progression of GON, functional vision loss often precedes detection by standard automated perimetry (SAP).9 Changes in contrast sensitivity (CS) can be noted before significant visual acuity loss, visible retinal nerve fiber layer (RNFL) damage, or SAP visual field defects.10 Various studies have documented enhanced central CS in patients with POAG after undergoing medical treatment for reduction in IOP with topical drugs or surgical reduction of IOP.6,8,11,12 All topical multi-dose formulations of anti-glaucoma drugs have preservatives for keeping them sterile and for extending their shelf-life. Preservatives are of two main categories, detergents or oxidizing agents. Detergent type preservatives, e.g., benzalkonium chloride (BAK) can be toxic to the ocular surface, especially where exposure is going to be lifelong and repeated due to the slowly progressive nature of the disease, or if there is pre existing ocular surface disease (OSD).13 Dry eye disease (DED) induced by preservatives arises from a intricate interplay of various contributing factors involving ocular surface, blinking rate and tear film stability. Many antiglaucoma drugs are now using alternative 1 agents to BAK, such as Polyquad or ionic buffer, to have a favourable ocular surface profile.14 OSD induced dry eye can compromise the CS as well. In the current study we plan to see the effect of two different types of, BAK free, prostaglandin analogue (PGA), Travoprost, 0.004%, on CS as well as the ocular surface. Travoprost is a synthetic lipophilic isopropyl ester prodrug of the active compound travoprost free acid, a prostaglandin F2alpha analog with anti-glaucoma property. Travoprost is hydrolysed to a free acid by corneal esterases, and then it selectively stimulates the prostaglandin F (FP prostanoid) receptor, thereby increasing the uveoscleral outflow that leads to a reduction of IOP in open angle glaucomas and ocular hypertensives. It is instilled once daily at bedtime. Patients will be randomly assigned to a travoprost formulation preserved with Polyquad [Polyquaternium-1; PQ], TRAVATAN (Novartis Healthcare Pvt. Ltd.) and another formulation preserved with Ionic buffered solution, TRAVOFLO (Ipca Laboratories Ltd.). In the current study we plan to use the Spaeth Richman Contrast Sensitivity Test (SPARCS), an online computerized assessment incorporating multiple answer choices and a bracketing technique to determine both central and peripheral CS threshold. Tear film parameters, Dry Eye Questionnaire-5 (DEQ-5) and Ocular Surface Disease Index (OSDI) will be employed to ascertain changes in ocular surface at baseline and at 3 months after institution of therapy with two different BAK free formulations of Travoprost. In terms of discriminating symptoms of dry eye, performance of the DEQ-5 questionnaire has been found to be comparable to the OSDI questionnaire.