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Indian Journal of Ophthalmology Jun 2022The burden of irreversible vision loss from Glaucoma continues to rise. While the disease pathogenesis is not well understood, intraocular pressure (IOP) is the only... (Review)
Review
The burden of irreversible vision loss from Glaucoma continues to rise. While the disease pathogenesis is not well understood, intraocular pressure (IOP) is the only modifiable risk factor identified to prevent glaucomatous vision loss. Medical management remains the first-line of treatment in most adult glaucomas and the evolution of medical therapy for glaucoma has followed an exponential curve. This review tracks the rapid development of new medications and drug delivery systems in the recent years. Introduction of Rho kinase inhibitors with an entirely new mechanism of action from that of the currently used anti glaucoma medications has been a significant milestone. Latanoprostene Bunod is a novel, single molecule which provides two active metabolites that work through two different pathways for reducing intra ocular pressure. Bimatoprost implants and travoprost punctum plugs attempt to ease chronic medication use in glaucoma patients. Nanotechnology is an evolving route of drug delivery. Role of cannabinoids in medical management of glaucoma remain equivocal. The relatively short term effect on IOP, the risks of developing tolerance and side effects impacting patients' neurocognitive health greatly outweigh the potential benefit. Research on Latrunculin B, Adenosine receptor agonists, Specific gene silencing and Stem cell therapy are poised to make an impact on glaucoma treatment. While there is some evidence to support the role of Brimonidine in neuroprotection, further research is needed to clarify the role of Memantine and Neurotrophins. Evidence for benefit from dietary supplementation with Alpha lipoic acid, Forskolin , and Ginko Biloba is limited.
Topics: Antihypertensive Agents; Bimatoprost; Glaucoma; Humans; Intraocular Pressure; Tonometry, Ocular
PubMed: 35647957
DOI: 10.4103/ijo.IJO_2239_21 -
Current Oncology (Toronto, Ont.) Mar 2023Millions of new cancer patients receive chemotherapy each year. In addition to killing cancer cells, chemotherapy is likely to damage rapidly proliferating healthy... (Review)
Review
Millions of new cancer patients receive chemotherapy each year. In addition to killing cancer cells, chemotherapy is likely to damage rapidly proliferating healthy cells, including the hair follicle keratinocytes. Chemotherapy causes substantial thinning or loss of hair, termed chemotherapy-induced alopecia (CIA), in approximately 65% of patients. CIA is often ranked as one of the most distressing adverse effects of chemotherapy, but interventional options have been limited. To date, only scalp cooling has been cleared by the US Food and Drug Administration (FDA) to prevent CIA. However, several factors, including the high costs not always covered by insurance, preclude its broader use. Here we review the current options for CIA prevention and treatment and discuss new approaches being tested. CIA interventions include scalp cooling systems (both non-portable and portable) and topical agents to prevent hair loss, versus topical and oral minoxidil, photobiomodulation therapy (PBMT), and platelet-rich plasma (PRP) injections, among others, to stimulate hair regrowth after hair loss. Evidence-based studies are needed to develop and validate methods to prevent hair loss and/or accelerate hair regrowth in cancer patients receiving chemotherapy, which could significantly improve cancer patients' quality of life and may help improve compliance and consequently the outcome of cancer treatment.
Topics: United States; Humans; Quality of Life; Alopecia; Cryotherapy; Neoplasms; Antineoplastic Agents
PubMed: 37185388
DOI: 10.3390/curroncol30040275 -
Ophthalmology Dec 2020To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-μg bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-μg bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular hypertension (OHT) after initial and repeated administrations.
DESIGN
Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study.
PARTICIPANTS
Adults with OAG or OHT in each eye, open iridocorneal angle inferiorly in the study eye, and study eye baseline IOP (hour 0; 8 am) of 22-32 mmHg after washout.
METHODS
Study eyes received bimatoprost implant 10 μg (n = 198) or 15 μg (n = 198) on day 1 with readministration at weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n = 198). Intraocular pressure was measured at hours 0 and 2 at each visit.
MAIN OUTCOME MEASURES
Primary end points were IOP and change from baseline IOP through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD).
RESULTS
Both dose strengths of bimatoprost implant were noninferior to timolol in IOP lowering after each administration. Mean diurnal IOP was 24.0, 24.2, and 23.9 mmHg at baseline and from 16.5-17.2, 16.5-17.0, and 17.1-17.5 mmHg through week 12 in the 10-μg implant, 15-μg implant, and timolol groups, respectively. The incidence of corneal and inflammatory TEAEs of interest (e.g., corneal endothelial cell loss, iritis) was higher with bimatoprost implant than timolol and highest with the 15-μg dose strength. Incidence of corneal TEAEs increased after repeated treatment; with 3 administrations at fixed 16-week intervals, incidence of ≥20% CECD loss was 10.2% (10-μg implant) and 21.8% (15-μg implant). Mean best-corrected visual acuity (BCVA) was stable; 3 implant-treated subjects with corneal TEAEs had >2-line BCVA loss at their last visit.
CONCLUSIONS
Both dose strengths of bimatoprost implant met the primary end point of noninferiority to timolol through week 12. One year after 3 administrations, IOP was controlled in most subjects without additional treatment. The risk-benefit assessment favored the 10-μg implant over the 15-μg implant. Ongoing studies are evaluating other administration regimens to reduce the potential for CECD loss. The bimatoprost implant has potential to improve adherence and reduce treatment burden in glaucoma.
Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Bimatoprost; Double-Blind Method; Drug Implants; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Timolol; Tonometry, Ocular; Vitreous Body; Young Adult
PubMed: 32544560
DOI: 10.1016/j.ophtha.2020.06.018 -
Dermatology Practical & Conceptual Jul 2020Chemotherapy-induced alopecia (CIA) is one of the most dramatic side effects of chemotherapy. Currently no guidelines are available for its prevention and treatment.... (Review)
Review
BACKGROUND
Chemotherapy-induced alopecia (CIA) is one of the most dramatic side effects of chemotherapy. Currently no guidelines are available for its prevention and treatment. Several devices and drugs are used, but results are often disappointing.
AIMS
Our aim is to analyze drugs and devices proposed in the literature for prevention and treatment of CIA induced by cytotoxic drugs and to discuss the evidenced-based opinion.
METHODS AND RESULTS
Scalp cooling is the only agent that has been approved by the US Food and Drug Administration for CIA prevention. Minoxidil and bimatoprost should not be used during chemotherapy administration, but they can be used after chemotherapy discontinuation to obtain greater regrowth.
CONCLUSIONS
Therapy should always be modulated for the patient and no fixed protocol should be used. Trichoscopy and trichogram could be useful tools in supporting this treatment.
PubMed: 32642317
DOI: 10.5826/dpc.1003a74 -
Drugs & Aging Jun 2020Bimatoprost implant (Durysta™), developed by Allergan, is a sustained-release drug delivery system containing bimatoprost, a prostaglandin analogue with ocular... (Review)
Review
Bimatoprost implant (Durysta™), developed by Allergan, is a sustained-release drug delivery system containing bimatoprost, a prostaglandin analogue with ocular hypotensive activity. The implant, administered intracamerally, involves the use of a biodegradable, solid polymer drug delivery system for slow, sustained drug release, designed to lower intraocular pressure (IOP) over a 4- to 6-months period. In March 2020, bimatoprost implant received its first approval, in the USA, for use to reduce IOP in patients with open angle glaucoma (OAG) or ocular hypertension (OHT). Allergan's clinical development programme for bimatoprost implant is ongoing. This article summarizes the milestones in the development of bimatoprost implant leading to this first approval for use in the reduction of IOP in patients with OAG or OHT.
Topics: Bimatoprost; Drug Approval; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Prostheses and Implants
PubMed: 32447639
DOI: 10.1007/s40266-020-00769-8 -
Indian Journal of Ophthalmology May 2023Glaucoma is a major cause of irreversible blindness worldwide. Reducing intraocular pressure (IOP) is currently the only approach to prevent further optic nerve head... (Review)
Review
Glaucoma is a major cause of irreversible blindness worldwide. Reducing intraocular pressure (IOP) is currently the only approach to prevent further optic nerve head damage. Pharmacotherapy is the mainstay of treatment for glaucoma patients. In recent years, a significant milestone in glaucoma treatment has been a transition to prostaglandin analogs (PGAs) as the first line of drugs. The rapid shift from traditional β-blockers to PGAs is primarily due to their excellent efficacy, convenient once-a-day usage, better diurnal control of IOP, and systemic safety profiles. This review article aims to provide information regarding the various PGAs in practice and also the newer promising drugs.
Topics: Humans; Bimatoprost; Cloprostenol; Travoprost; Latanoprost; Prostaglandins F, Synthetic; Ophthalmology; Antihypertensive Agents; Amides; Prostaglandins, Synthetic; Glaucoma; Intraocular Pressure
PubMed: 37203029
DOI: 10.4103/IJO.IJO_2706_22 -
Journal of Ocular Pharmacology and... May 2020Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade extracellular matrix (ECM) components such as collagen and have important roles in... (Review)
Review
Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade extracellular matrix (ECM) components such as collagen and have important roles in multiple biological processes, including development and tissue remodeling, both in health and disease. The activity of MMPs is influenced by the expression of MMPs and tissue inhibitors of metalloproteinase (TIMPs). In the eye, MMP-mediated ECM turnover in the juxtacanalicular region of the trabecular meshwork (TM) reduces outflow resistance in the conventional outflow pathway and helps maintain intraocular pressure (IOP) homeostasis. An imbalance in the MMP/TIMP ratio may be involved in the elevated IOP often associated with glaucoma. The prostaglandin analog/prostamide (PGA) class of topical ocular hypotensive medications used in glaucoma treatment reduces IOP by increasing outflow through both conventional and unconventional (uveoscleral) outflow pathways. Evidence from and studies using animal models and anterior segment explant and cell cultures indicates that the mechanism of IOP lowering by PGAs involves increased MMP expression in the TM and ciliary body, leading to tissue remodeling that enhances conventional and unconventional outflow. PGA effects on MMP expression are dependent on the identity and concentration of the PGA. An intracameral sustained-release PGA implant (Bimatoprost SR) in development for glaucoma treatment can reduce IOP for many months after expected intraocular drug bioavailability. We hypothesize that the higher concentrations of bimatoprost achieved in ocular outflow tissues with the implant produce greater MMP upregulation and more extensive, sustained MMP-mediated target tissue remodeling, providing an extended duration of effect.
Topics: Administration, Topical; Animals; Antihypertensive Agents; Bimatoprost; Ciliary Body; Collagen; Drug Implants; Extracellular Matrix; Glaucoma; Homeostasis; Humans; Intraocular Pressure; Matrix Metalloproteinases; Models, Animal; Prostaglandins, Synthetic; Tissue Inhibitor of Metalloproteinases; Trabecular Meshwork
PubMed: 32233938
DOI: 10.1089/jop.2019.0146 -
Journal of Current Glaucoma Practice 2023This review summarizes current data on Rho-kinase (ROCK) inhibitors use in ocular diseases, primarily glaucoma. (Review)
Review
AIM
This review summarizes current data on Rho-kinase (ROCK) inhibitors use in ocular diseases, primarily glaucoma.
BACKGROUND
Translational research over the last decade culminating in the development of ROCK inhibitors has provided a much-needed shot in the arm to glaucoma pharmacopeia. ROCK pathway is intricately involved in cytoskeletal modulation with action on cell morphology, cell motility, cell adhesion, cell apoptosis, and smooth muscle contraction. This cytoskeletal modulation property has been utilized to modify trabecular meshwork (TM) resistance, resulting in the discovery of ROCK inhibitors to increase trabecular outflow.
REVIEW RESULTS
Multicentric trials on ROCK inhibitors for antiglaucoma medications are summarized. The focus is on linking pharmacological action to the clinical utility of these drugs. While the Rho Kinase Elevated intraocular Pressure (IOP) Treatment (ROCKET) trials compared monotherapy with ROCK inhibitor netarsudil vs timolol, MERCURY trials compared a fixed dose combination of latanoprost and ROCK inhibitor netarsudil [fixed combination netarsudil-latanoprost (FCNL)] vs monotherapy with either and bimatoprost-timolol combination. While ROCKET trials showed ROCK inhibitors to be non-inferior to timolol, MERCURY trials showed FCNL achieving a much greater IOP reduction than monotherapy with either. Conjunctival hyperemia was the most common side effect reported with ROCK inhibitor use.
CONCLUSION
Moderate efficacy of ROCK inhibitors with a common side effect of conjunctival hyperemia, makes it an adjunctive antiglaucoma drug of choice and not a first-line therapy.
CLINICAL SIGNIFICANCE
ROCK inhibitors' action on diseased TM is more physiological compared to available antiglaucoma medications that either reduce aqueous secretion or enhance uveoscleral outflow. The property of ROCK inhibition to stabilize the endothelium of both retinal vasculature and cornea has opened a new chapter in the treatment of diabetic retinopathy and corneal decompensation.
HOW TO CITE THIS ARTICLE
Singh K, Singh A. Rho-kinase Inhibitors in Ocular Diseases: A Translational Research Journey. J Curr Glaucoma Pract 2023;17(1):44-48.
PubMed: 37228304
DOI: 10.5005/jp-journals-10078-1396