Short- and long-term safety of glaucoma drugs

Glaucoma, a leading cause of blindness worldwide, is a chronic neurodegenerative disorder. Patients with glaucoma may require long-term administration of intraocular pressure (IOP)-lowering medications. These medications belong to several classes of molecules including β-adrenergic blockers, cholinergic agents, α-adrenergic agonists, carbonic anhydrase inhibitors and ocular hypotensive lipids. Most adverse effects associated with IOP-lowering medications are mild and ocular in nature; however, several of them are associated with systemic risks as well as serious ocular effects, especially following chronic use. The following review discusses the acute and long-term effects of commonly used IOP-lowering medications.     

Short- and long-term safety of glaucoma drugs

Glaucoma, a leading cause of blindness worldwide, is a chronic neurodegenerative disorder. Patients with glaucoma may require long-term administration of intraocular pressure (IOP)-lowering medications. These medications belong to several classes of molecules including beta-adrenergic blockers, cholinergic agents, alpha-adrenergic agonists, carbonic anhydrase inhibitors and ocular hypotensive lipids. Most adverse effects associated with IOP-lowering medications are mild and ocular in nature; however, several of them are associated with systemic risks as well as serious ocular effects, especially following chronic use. The following review discusses the acute and long-term effects of commonly used IOP-lowering medications.     

Glaucoma and its treatment: a review.

PURPOSE: A review of glaucoma and its treatment is presented. SUMMARY: Glaucoma is a common eye disease that can cause irreversible blindness if left undiagnosed and untreated. Glaucoma is a leading cause of blindness in the United States and other industrialized countries. In most cases, the symptoms of early-stage glaucoma are minimal or nonexistent. There are several different types of glaucoma, and they have been classically divided into the categories of primary or secondary open-angle or angle-closure glaucoma. Secondary forms of glaucoma are caused by various ocular or systemic diseases. Every available treatment to prevent progressive glaucomatous optic neuropathy has potential adverse effects and involves a certain amount of risk and financial expense. Conventional first-line treatment of glaucoma usually begins with the use of a topical selective or nonselective beta-blocker or a topical prostaglandin analog. Second-line drugs of choice include alpha-agonists and topical carbonic anhydrase inhibitors. Parasympathomimetic agents, most commonly pilocarpine, are considered third-line treatment options. For patients who do not respond to antiglaucoma medications, laser trabeculoplasty and incisional surgery are further methods that can be used to lower intraocular pressure. The results of clinical trials have reaffirmed the utility of antiglaucoma medications in slowing the progression of the disease. CONCLUSION: Glaucoma is a common eye disease that is usually associated with an elevated intraocular pressure. Treatment options for patients with glaucoma include medications, laser therapy, and incisional surgery. The risks and benefits of each type of treatment must be carefully considered to maximize the treatment's benefits while minimizing adverse effects.     

Emerging drugs to treat glaucoma: targeting prostaglandin F and E receptors

Introduction: Commercially available prostaglandin analogues (PGAs) activate the prostaglandin F receptor (FP) reducing intraocular pressure (IOP), thereby stabilizing glaucomatous optic neuropathy. Poor adherence with eye drops and intolerance impact treatment success.

Areas covered: We review developments in drug formulation and delivery, including punctal plugs, topical ring inserts, subconjunctival injections and inserts, and intraocular inserts. We also outline research into new fixed dose combinations that include prostaglandin analogues and preservative-free versions of established agents.

Expert opinion: Glaucoma is a chronic, usually progressive disease that causes irreversible visual loss. As its prevalence increases exponentially with age, it has significant implications as the population ages. Health resources need to meet increased demand for glaucoma management resources, including monitoring and treating glaucoma suspects and patients and supporting those who have suffered visual disability. Several promising therapies are under investigation. Sustained-release prostaglandin analogues using alternate delivery methods are encouraging. Delivery routes may be more invasive than topical drops. Nanotechnological-release delivery of prostaglandin analogues could lower IOP effectively. Approaches like this would eliminate many of the adherence issues associated with daily topical PGA eye drop use.     

Emerging drugs for ocular hypertension

INTRODUCTION: Glaucoma is a prevalent ocular disease with characteristic optic disc and visual field changes. Globally, it is the second most common cause of visual disability, and the most common cause of irreversible and preventable blindness. Ocular hypertension (OH) occurs where intraocular pressure elevation occurs in the absence of glaucomatous disc and visual field changes. OH is a strong risk factor for glaucoma. Ocular hypotensive medications are the mainstay of glaucoma and OH treatment, and their use modifies the course of the disease by preventing onset and progression of damage. AREAS COVERED: Prostaglandin analogs, β-blockers, α-agonists, carbonic anhydrase inhibitors and parasympathomimetics are available in our glaucoma armamentarium and are reviewed. Novel agents have evolved as our understanding of the complex mechanisms involved in aqueous humor production and obstacles to aqueous outflow increases. Potential future candidates appear to act on enhancing trabecular meshwork outflow: the Rho-kinase inhibitors, ion-channel modulators and chelating agents. Further work is needed on other promising agents: serotonergics, melatonins, cannabinoids, adenosine agonists, components of the actomyosin system, nucleotide analogs and gene silencing. Methods to improve side effect profiles or efficacy of currently available therapies are also being developed. As glaucoma treatment adherence is poor, novel drug delivery methods might address this challenge. EXPERT OPINION: Although there are good intraocular pressure-lowering medications available, novel mechanisms and drug delivery modes may provide more effective glaucoma control in future.     

Ophthalmic drug discovery: novel targets and mechanisms for retinal diseases and glaucoma

Blindness affects 60 million people worldwide. The leading causes of irreversible blindness include age-related macular degeneration, retinal vascular diseases and glaucoma. The unique features of the eye provide both benefits and challenges for drug discovery and delivery. During the past decade, the landscape for ocular drug therapy has substantially changed and our knowledge of the pathogenesis of ophthalmic diseases has grown considerably. Anti-angiogenic drugs have emerged as the most effective form of therapy for age-related macular degeneration and retinal vascular diseases. Lowering intraocular pressure is still the mainstay for glaucoma treatment but neuroprotective drugs represent a promising next-generation therapy. This Review discusses the current state of ocular drug therapy and highlights future therapeutic opportunities.     

Management of glaucoma: focus on pharmacological therapy

Glaucoma represents a major cause of vision loss throughout the world. Primary open-angle glaucoma, the most common form of glaucoma, is a chronic, progressive disease often, though not always, accompanied by elevated intraocular pressure (IOP). In this disorder, retinal ganglion cell loss and excavation of the optic nerve head produce characteristic peripheral visual field deficits. Patients with normal-tension glaucoma present with typical visual field and optic nerve head changes, without a documented history of elevated IOP. A variety of secondary causes, such as pigment dispersion syndrome and ocular trauma, can result in glaucoma as well. Treatment of all forms of glaucoma consists of reducing IOP. With proper treatment, progression of this disease can often be delayed or prevented. Treatment options for glaucoma include medications, laser therapy and incisional surgery. Laser techniques for the reduction of IOP include argon laser trabeculoplasty and selective laser trabeculoplasty. Both techniques work by increasing outflow of aqueous humour through the trabecular meshwork. Surgical options for glaucoma treatment include trabeculectomy, glaucoma drainage tube implantation and ciliary body cyclodestruction. While each of these types of procedures is effective at lowering IOP, therapy usually begins with medications. Medications lower IOP either by reducing the production or by increasing the rate of outflow of aqueous humour within the eye. Currently, there are five major classes of drugs used for the treatment of glaucoma: (i) cholinergics (acetylcholine receptor agonists); (ii) adrenoceptor agonists; (iii) carbonic anhydrase inhibitors (CAIs); (iv) beta-adrenoceptor antagonists; and (v) prostaglandin analogues (PGAs). Treatment typically begins with the selection of an agent for IOP reduction. Although beta-adrenoceptor antagonists are still commonly used by many clinicians, the PGAs are playing an increasingly important role in the first-line therapy of glaucoma. Adjunctive agents, such as alpha-adrenoceptor agonists and CAIs are often effective at providing additional reduction in IOP for patients not controlled on monotherapy. As with any chronic disease, effective treatment depends on minimising the adverse effects of therapy and maximising patient compliance. The introduction of a variety of well tolerated and potent medications over the past few years now allows the clinician to choose a treatment regimen on an individual patient basis and thereby treat this disorder more effectively.     

Topical bimatoprost: a review of its use in open-angle glaucoma and ocular hypertension

Bimatoprost, a synthetic prostamide analogue, is a new ocular hypotensive agent indicated for the second-line treatment of open-angle glaucoma and ocular hypertension. The drug is formulated as a 0.03% ophthalmic solution. Bimatoprost lowers intraocular pressure (IOP) by increasing aqueous humour outflow. When applied topically once daily in patients with ocular hypertension or glaucoma, bimatoprost 0.03% significantly reduced IOP. Mean IOP was reduced by approximately 7.5 to 9.2mm Hg 12 hours after drug administration in randomised clinical trials. The reduction in IOP was maintained throughout the 24-hour dosage interval. Once-daily treatment with bimatoprost 0.03% was found to be significantly more effective than timolol 0.5% (administered twice daily as an ophthalmic solution or once daily as a gel-forming solution) in randomised comparative trials in patients with ocular hypertension and glaucoma. Furthermore, after 1 to 6 months' treatment, the percentage of patients reaching a target IOP of < or =17mm Hg was significantly greater in the bimatoprost-treated groups than in those receiving timolol. Bimatoprost 0.03% ophthalmic solution was found to be at least as effective as topical latanoprost 0.005% administered once daily in two clinical trials. Reductions in IOP 16 and 20 hours postdose were greater in patients treated with bimatoprost, indicating superior control of IOP at timepoints throughout the dosage interval. In patients refractory to beta-blocker therapy, treatment with bimatoprost 0.03% produced greater reductions in diurnal IOP measurements than combination therapy with topical dorzolamide 2%/timolol 0.5%; approximately twice as many bimatoprost 0.03% recipients achieved an IOP of < or =16mm Hg. The most commonly reported adverse effect during clinical trials of once-daily bimatoprost 0.03% was conjunctival hyperaemia which occurred in 42 to 46% of patients treated. However, most cases were mild and only 1 to 4% of patients withdrew from treatment as a result. Overall withdrawal rates as a result of adverse events during clinical trials ranged from 2.6 to 7%. Bimatoprost has been reported to cause changes in the pigmentation of the periorbital skin, eyelashes and iris, and increase eyelash growth. The long-term consequences of these effects are unknown. Cardiopulmonary adverse effects, which have been associated with the use of beta-blockers such as timolol, were not reported in clinical trials of bimatoprost. Thus, in clinical trials of up to 1-year duration, bimatoprost 0.03% has been found to be effective in significantly lowering IOP and is generally well tolerated. It provides an alternative treatment option for patients in whom beta-blockers are contraindicated. Furthermore, bimatoprost provides an effective second-line treatment option in patients who do not achieve target IOP with other topical ocular hypotensive agents, or who experience unacceptable adverse effects. Wider clinical use of this drug will establish the place of bimatoprost in the treatment of open-angle glaucoma and ocular hypertension.     

Effects of common topical antiglaucoma medications on the ocular surface, eyelids and periorbital tissue

Glaucoma affects millions of people around the world. With the baby boom generation aging, the number of people affected by primary open-angle glaucoma in the US is expected to reach 3.3 million by 2020, and about half may not know they have the disease. The treatment of most forms of glaucoma includes the use of topical agents that enhance aqueous humour outflow, reduce aqueous production, or both. Topical intraocular pressure-lowering drugs must penetrate across the tissues of the eye to reach their therapeutic targets. Often, these tissues show the first signs and symptoms of drug toxicity and adverse effects. These include eyelid dermatitis, malpositions, lacrimal system scarring, ocular discomfort upon instillation, tear film instability, conjunctival inflammation, subconjunctival fibrosis, conjunctival epithelium changes, and corneal surface and endothelial impairment. For these reasons, ophthalmologists should evaluate the risks and benefits of ophthalmic medications before initiating therapy, identify the minimum dosages necessary to achieve a therapeutic benefit, and monitor patients for local and systemic adverse effects. Adverse events may be reduced by changing to a different class of topical medication, using corticosteroids, lubricating the eyes frequently, and reducing exposure to preservatives. This in turn can lead to higher levels of adherence to antiglaucoma therapy, improved outcomes and a reduction in the costs associated with long-term glaucoma complications. This article reviews the ocular adverse effects associated with the various classes of topical antiglaucoma drugs, with a particular focus on the ocular surface, eyelids and periorbital tissue.     

Metabolism of ophthalmic timolol: new aspects of an old drug

Glaucoma is a common eye disease that can cause irreversible blindness if not diagnosed and treated in the early stages of progression. This disease is often, albeit not always, associated with increased intraocular pressure, which is also the most important risk factor for glaucoma. Currently, the only treatment option of glaucoma is reduction of intraocular pressure. A β-adrenergic antagonist, timolol, has been used for the treatment of glaucoma and increased intraocular pressure for more than 30 years and still remains the drug of choice. Locally, timolol is well tolerated. However, it has been reported that approximately 80% of a topically administered eye drop is systemically absorbed. Thus, ophthalmic timolol may cause severe adverse cardiovascular and respiratory effects. On the basis of the aforementioned situation, it is somewhat surprising to notice that the metabolism of timolol has only recently been studied in detail even though the drug has been used for decades. Earlier clinical studies have suggested that timolol is metabolized by CYP2D6, an important member of the cytochrome P450 family. Our recent in vitro studies demonstrated convincingly that CYP2D6 is the main enzyme contributing to timolol metabolism, although also CYP2C19 may have a minor role. Liver is the principal site of timolol metabolism, because - according to our recent findings - only negligible amounts of CYP2D6 are expressed in human ocular tissues. After topical administration, systemic timolol concentrations may be high enough to cause cardiovascular and respiratory adverse effects especially in patients who are CYP2D6 poor metabolizers or use concomitant CYP2D6 inhibitors.     

Glaucoma: a review of adjunctive therapy and new management strategies

Glaucoma is a major cause of vision loss throughout the world. Treatment for glaucoma consists of reducing intraocular pressure (IOP) to an acceptable target range to prevent further optic nerve damage. Typically, this involves the selection of a topical IOP-lowering agent. Five major classes of glaucoma medications are presently available for clinical use. These include alpha-adrenergic agonists, beta-adrenergic antagonists (beta-blockers), carbonic anhydrase inhibitors (CAIs), cholinergics and prostaglandin analogs (PGAs). Although beta-blockers enjoyed great success as first-line glaucoma therapy for many years, recently the PGAs have gained favor as the initial treatment of choice for most patients. Although the PGAs offer robust IOP reduction as monotherapy, a significant number of patients will require an adjunctive agent for adequate IOP control. Recent studies have demonstrated that alpha-agonists, beta-blockers and CAIs can be used safely and effectively as adjunctive therapy for patients being treated with a PGA. Comparison studies are beginning to appear in the literature to help determine which adjunctive agent is the most effective when used in combination with a PGA. Additional IOP-lowering efficacy with adjunctive therapy does have limitations, particularly with the addition of a third or fourth agent. For those patients on maximal tolerated medical therapy who still need additional IOP reduction, other available options include laser trabeculoplasty and filtration surgery.     

Glaucoma: a review of adjunctive therapy and new management strategies

Glaucoma is a major cause of vision loss throughout the world. Treatment for glaucoma consists of reducing intraocular pressure (IOP) to an acceptable target range to prevent further optic nerve damage. Typically, this involves the selection of a topical IOP-lowering agent. Five major classes of glaucoma medications are presently available for clinical use. These include α-adrenergic agonists, β-adrenergic antagonists (β-blockers), carbonic anhydrase inhibitors (CAIs), cholinergics and prostaglandin analogs (PGAs). Although β-blockers enjoyed great success as first-line glaucoma therapy for many years, recently the PGAs have gained favor as the initial treatment of choice for most patients. Although the PGAs offer robust IOP reduction as monotherapy, a significant number of patients will require an adjunctive agent for adequate IOP control. Recent studies have demonstrated that α-agonists, β-blockers and CAIs can be used safely and effectively as adjunctive therapy for patients being treated with a PGA. Comparison studies are beginning to appear in the literature to help determine which adjunctive agent is the most effective when used in combination with a PGA. Additional IOP-lowering efficacy with adjunctive therapy does have limitations, particularly with the addition of a third or fourth agent. For those patients on maximal tolerated medical therapy who still need additional IOP reduction, other available options include laser trabeculoplasty and filtration surgery.     

Topical dorzolamide 2%/timolol 0.5% ophthalmic solution: a review of its use in the treatment of glaucoma and ocular hypertension

Topically administered dorzolamide 2%/timolol 0.5% (dorzolamide/timolol ophthalmic solution; Cosopt) is a fixed combination of two ocular hypotensive drugs (the carbonic anhydrase inhibitor dorzolamide and the beta-adrenoceptor antagonist timolol) that have an additive effect on lowering intraocular pressure (IOP) when administered together. This product is indicated for the treatment of elevated IOP in patients with open-angle glaucoma or ocular hypertension (OH) who are insufficiently responsive to topical beta-adrenoceptor antagonist monotherapy. As such, it can be considered for use in individuals who, as a consequence of failing to achieve target IOP with beta-adrenoceptor antagonist monotherapy, require the addition or substitution of another class of topical antiglaucoma medication. Clinical trials have demonstrated that dorzolamide/timolol (1 drop per eye twice daily) is an effective and generally well tolerated fixed combination for lowering IOP in patients with open angle glaucoma or OH, including individuals uncontrolled on beta-adrenoceptor antagonist monotherapy. Compared with concomitant therapy with the individual components, the primary advantage of fixed combination dorzolamide/timolol is convenience.     

New pharmacotherapy for the treatment of glaucoma

Introduction: Glaucoma is the second leading cause of blindness in the world and current pharmacotherapies for glaucoma have remained relatively unchanged (with the exception of fixed combinations of previously available medications) since the mid-1990s with the development of prostaglandin analogues. Now, with both new formulations and new classes of medications with novel mechanisms of action, the medical therapy of glaucoma may be heralding a new dawn in medical management.

Areas covered: This review outlines new topical therapies for intraocular pressure (IOP) lowering treatment, in addition to new formulations, preservative-free options, and advances in glaucoma medical therapy delivery. We performed a comprehensive search for published studies for glaucoma medical therapy using the electronic database PubMed. A manual search for each therapy or delivery system was also performed.

Expert commentary: These advances in glaucoma therapy have the potential to overcome many barriers to glaucoma’s medical care, particularly in terms of adherence. However, both time and research are needed to prove the relative efficacy and safety of these new pharmacotherapies and products, helping us decide their role in the treatment of elevated intraocular pressure. We are hopeful that these new developments in therapy may bring more options for glaucoma medical therapy.     

Overview of the [corrected] travoprost /timolol BAK-free fixed combination

INTRODUCTION: Glaucoma is the second leading cause of blindness globally, representing a significant public health concern. More than 60 million people are affected by glaucoma worldwide; as this population ages, the number is expected to increase. Glaucoma is a collection of heterogeneous diseases sharing common clinical characteristics. The goal of treatment is to prevent significant visual dysfunction through reduction of intraocular pressure (IOP). AREAS COVERED: This is a review of the current literature about combination therapeutic regimens for the reduction of IOP, focusing on the risk : benefit profile of a fixed-combination therapy using travoprost and timolol. EXPERT OPINION: Since the debut of prostaglandin analogues in the 1990s, only modest innovation has occurred in glaucoma pharmacology. A growing body of research has established that the preservative benzalkonium chloride (BAK) might not be the benign contributor expected of excipient ingredients. Thus, BAK-free treatments were developed, with the goal of IOP reduction without furthering ocular surface disease symptoms. The BAK-free travoprost/timolol combination represents an important addition to glaucoma medication options and may fill an unmet need in this therapeutic arena.     

Trabecular meshwork as a new target for the treatment of glaucoma

Glaucoma, a group of optic neuropathies, is one of the leading causes of irreversible blindness in the world. It is characterized by degeneration of the optic nerve and progressive visual field loss, often associated with elevated intraocular pressure (IOP). In primary open-angle glaucoma, the most common form of the disease, IOP occurs as a result of abnormally increased resistance to drainage of aqueous humor through the conventional outflow system, which comprises the trabecular meshwork and the Schlemm's canal. The pharmacological treatment of glaucoma has been classically aimed at lowering elevated IOP, either decreasing the production of aqueous humor or improving its outflow. Increasing knowledge of trabecular meshwork physiology shows that this tissue has unique morphologic and functional properties involved in the regulation of aqueous humor outflow. Although trabecular meshwork physiology is yet to be fully revealed, ion channels involved in cell contractility or cell volume regulation, or those capable of responding to high pressure, have been described and may be considered promising pharmacological targets for the treatment of glaucoma. The cytoskeleton architecture of the trabecular meshwork cell is thought to be an important regulator of aqueous humor outflow. Gene technology directed at discovering genes linked to the development of glaucoma or to those upregulated in response to elevated IOP is challenging research but provides an insight into future gene therapy. New tools to study trabecular meshwork physiology have recently been developed, including the use of lentivirus for gene delivery or fusion proteins with a protein transduction domain. These vectors are targeted specifically to the trabecular meshwork and are powerful techniques with broad applications for future gene therapy or as new forms of drug delivery.     

Brinzolamide : a review of its use in the management of primary open-angle glaucoma and ocular hypertension

Brinzolamide is a highly specific carbonic anhydrase (CA) inhibitor which lowers intraocular pressure (IOP) by reducing the rate of aqueous humour formation. Formulated as a 1% ophthalmic suspension (Azopt) and administered twice or three times daily, brinzolamide is indicated for the topical management of primary open-angle glaucoma (POAG) and ocular hypertension (OH) as either monotherapy or adjunctive therapy with topical beta-blockers. As monotherapy in patients with POAG or OH, brinzolamide 1% demonstrated IOP-lowering efficacy that was significantly greater than placebo, equivalent to three-times-daily dorzolamide 2% but significantly lower than twice-daily timolol 0.5%. Brinzolamide 1% was equally effective in twice- and three-times-daily regimens producing diurnal mean IOP reductions from baseline in the range of 13.2-21.8%. When used adjunctively twice daily with timolol 0.5%, brinzolamide 1% was as effective as dorzolamide 2% and superior to placebo in lowering IOP in patients with POAG or OH. In clinical trials, brinzolamide 1% was well tolerated causing only nonserious adverse effects that were generally local, transient and mild to moderate in severity. The incidence of the most common adverse events associated with the use of brinzolamide 1% was either similar to (blurred vision and abnormal taste) or significantly lower than (ocular discomfort) with dorzolamide 2%. Topical brinzolamide 1% does not appear to produce the acid-base or electrolyte disturbances and severe systemic adverse effects characteristic of oral CA inhibitors. It can be used in patients unresponsive to beta-blockers or in whom beta-blockers are contraindicated. Brinzolamide 1% administered twice daily is among the least costly alternatives and adjuncts to beta-blocker therapy for glaucoma and is generally associated with less direct medical cost than dorzolamide. CONCLUSION: Brinzolamide 1% ophthalmic suspension administered twice or three times daily, as monotherapy or adjunctive therapy with topical beta-blockers, has good IOP-lowering efficacy in patients with POAG or OH that is equivalent to that of dorzolamide 2% (three times daily as monotherapy, twice daily as adjunctive therapy). Brinzolamide is generally well tolerated and does not produce the systemic adverse effects associated with oral CA inhibitors. It can be used in patients who are unresponsive to, intolerant of, or unable to receive, ophthalmic beta-blockers. Thus, brinzolamide, either as monotherapy or adjunctive therapy with topical beta-blockers, should be regarded as a good second-line option in the pharmacological management of POAG and OH, and may be preferred over dorzolamide because of significantly less ocular discomfort.     

Bimatoprost – a review

Bimatoprost is a synthetic prostamide analog that is efficacious in the treatment of open-angle glaucoma, ocular hypertension and other forms of glaucoma. It reduces intraocular pressure (IOP) by increasing uveoscleral and trabecular outflow. When used as a 0.03% topical preparation once daily, it demonstrates sustained lowering of IOP of 7 – 8 mmHg over a 24-h period. The drug has been found to be more effective than timolol. In some studies it has shown greater ability to lower IOP when compared with other prostaglandin analogs; whereas in others all three clinically used prostaglandin analogs were found to be equally effective. It shows good IOP reduction when used in combination with other glaucoma medications. A common side effect includes mild conjunctival hyperemia, which is generally reversible. Other side effects include periorbital pigmentation, discomfort, ocular surface hyperemia and skin changes. Pharmacoeconomic data indicate that bimatoprost is cost effective in the treatment of open-angle glaucoma.     

Newer approaches for optimal bioavailability of ocularly delivered drugs: review

Eye diseases can cause discomfort and anxiety in patients, with the ultimate fear of loss of vision and facial disfigurement. Many regions of the eye are relatively inaccessible to systemically administered drugs and, as a result, topical drug delivery remains the preferred route in most cases. Drugs may be delivered to treat the precorneal region for conjunctivitis and blepharitis, or to provide intraocular diseases such as glaucoma, uveitis, and cytomegalovirus retinitis. Most of the ophthalmic formulation strategies aim at maximizing ocular drug permeability through prolongation of the drug residence time in the cornea and conjunctival sac, as well as minimizing precorneal drug loss. The conventional topical ocular drug delivery systems show drawbacks such as increased precorneal elimination and high variability in efficacy. Attempts have been made to overcome these problems and enhance ocular bioavailability by the development of newer drug delivery systems. This review is concerned with classification, recent findings and applications and biocompatibility of newer drug delivery systems for the treatment of ocular diseases.