Tolerability of Current Treatments for Dry Eye Disease: A Review of Approved and Investigational Therapies.

Dry eye disease (DED) is a common, multifactorial ocular disease impacting 5% to 20% of people in Western countries and 45% to 70% in Asian countries. Despite the prevalence of DED and the number of treatment approaches available, signs and symptoms of the disease continue to limit the quality of life for many patients. Standard over-the-counter treatment approaches and behavior/environmental modifications may help some cases but more persistent forms often require pharmacological interventions. Approved and investigational pharmaceutical approaches attempt to treat the signs and symptoms of DED in different ways and tend to have varying tolerability among patients. While several pharmacological approaches are the standard for persistent and severe disease, mechanical options provide alternate treatment modalities that attempt to balance efficacy and comfort. Newer approaches target the causes of DED, utilizing novel delivery methods to minimize irritation and adverse events. Here, we review approved and investigational approaches to treating DED and compare patient tolerability.

Current state and future perspectives in the diagnosis of eyelid margin disease: clinical review.

The eyelid margin is vital to ocular surface integrity. Much peer-reviewed literature has been established in eyelid margin inflammation, better known as blepharitis. The purpose was to review and understand the impact of eyelid margin disease. Anterior blepharitis causes inflammation at the eyelash base, ciliary follicles, and the palpebral skin. Posterior blepharitis occurs when there is inflammation with the posterior eyelid margin disease. In common usage, the term "blepharitis" used alone almost always refers to anterior blepharitis. Classification of eyelid margin disease should be based on etiopathogenesis, location, primary vs secondary, and chronicity. Blepharitis has several etiopathologies (infectious, inflammatory, and squamous). Meibomian gland dysfunction (MGD) can refer to the functional and/or structural problems with the meibomian gland. Meibomitis (or meibomianitis) occurs when there is inflammation associated with the MGD. The presence of blepharitis and/or MGD (with or without inflammation) can affect the ocular surface and thereby affect anterior segment and cataract surgeries. This review article evaluates the differential diagnoses of eyelid margin disease, including various forms of blepharitis, MGD, and meibomitis.

Eyelid margin disease (blepharitis and meibomian gland dysfunction): clinical review of evidence-based and emerging treatments.

Blepharitis is a common ophthalmic condition with multiple etiologies and no definitive, universal treatment. The treatment modalities for managing lid margin diseases vary depending on the disease's cause, location, and severity. For anterior blepharitis, management options include eyelid hygiene with warm compresses, eyelid scrubs, baby shampoo, and over-the-counter eyelid cleansers. Topical antibiotics and antibiotic-steroid combination drops/ointments for the eye and eyelid may accompany these. For posterior blepharitis/meibomian gland dysfunction (MGD), at-home warm compress or in-office administration of heat therapy/thermal pulsation treatment that aims to clear obstruction in the meibomian glands and restore meibum secretions to maintain a healthy tear film is recommended. In addition to the above treatment strategies, various other compounds to manage lid margin diseases are in the late stages of development. This review summarizes the available treatment modalities or those in the pipeline for treating blepharitis and MGD.

Demodex Blepharitis: A Comprehensive Review of the Disease, Current Management, and Emerging Therapies.

ABSTRACT: Demodex blepharitis is a common disease of the eyelid, affecting approximately 25 million Americans. This article reviews what is known about the mechanisms and impact of Demodex blepharitis, risk factors, signs and symptoms, diagnostic techniques, current management options, and emerging treatments. Demodex mites contribute to blepharitis in several ways: direct mechanical damage, as a vector for bacteria, and by inducing hypersensitivity and inflammation. Risk factors for Demodex blepharitis include increasing age, rosacea, and diabetes. The costs, symptom burden, and psychosocial effects of Demodex blepharitis are considerable. The presence of collarettes is pathognomonic for Demodex blepharitis. Redness, dryness, discomfort, foreign body sensation, lash anomalies, and itching are also hallmarks of the disease. Although a number of oral, topical, eyelid hygiene and device-based options have been used clinically and evaluated in studies for the management of Demodex blepharitis, none have been FDA approved to treat the disease. Recent randomized controlled clinical trials suggest that lotilaner ophthalmic solution, 0.25%, is a topical treatment with the potential to eradicate Demodex mites and eliminate collarettes and eyelid redness for an extended period.

ASCRS clinical advisory on intracameral moxifloxacin injection for infection prophylaxis.

Moxifloxacin solution is frequently injected at the conclusion of cataract surgery for endophthalmitis prophylaxis. 2 different concentrations are most commonly available in the United States for intracameral (IC) use: 0.5% (5 mg/mL) and 0.1% (1 mg/mL). The recommended volume to be injected is different for the 2 concentrations, and incorrect dosing can increase the risk of toxic anterior segment syndrome or endophthalmitis. In addition, the U.S. Food and Drug Administration recently published an alert regarding potential adverse events associated with intraocular compounded moxifloxacin. This clinical advisory reviews the optimal dosing of IC moxifloxacin based on current evidence.

Anti-Inflammatories in the Treatment of Dry Eye Disease: A Review.

Inflammation is an important driver of dry eye disease (DED) pathogenesis. An initial insult that results in the loss of tear film homeostasis can initiate a nonspecific innate immune response that leads to a chronic and self-sustaining inflammation of the ocular surface, which results in classic symptoms of dry eye. This initial response is followed by a more prolonged adaptive immune response, which can perpetuate and aggravate inflammation and result in a vicious cycle of chronic inflammatory DED. Effective anti-inflammatory therapies can help patients exit this cycle, and effective diagnosis of inflammatory DED and selection of the most appropriate treatment are therefore key to successful DED management and treatment. This review explores the cellular and molecular mechanisms of the immune and inflammatory components of DED, and examines the evidence base for the use of currently available topical treatment options. These agents include topical steroid therapy, calcineurin inhibitors, T cell integrin antagonists, antibiotics, autologous serum/plasma therapy, and omega-3 fatty acid dietary supplements.

Optimization of the Ocular Surface Through Treatment of Ocular Surface Disease Before Ophthalmic Surgery: A Narrative Review.

Ocular surface disease commonly exists in individuals requiring ophthalmic surgery and may compromise the structure and function of ocular surface components. Ophthalmic surgery may further affect the ocular surface by injuring the epithelium and sensory nerves, disrupting the tear film, or causing local inflammation. Medical management of ocular surface disease prior to ophthalmic surgery aids in reducing inflammation, resolving infection, improving epithelial pathology, stabilizing the tear film, and easing patient symptoms, promoting positive long-term outcomes and minimizing the incidence of postoperative complications. This review summarizes frequently encountered ocular surface diseases and available preoperative medical management options, discusses common ophthalmic surgeries and their effects on the ocular surface, examines potential postoperative complications, and defines recommendations for postoperative ocular surface maintenance.

Antibiotic susceptibility of bacterial pathogens isolated from the aqueous and vitreous humour in the Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) Surveillance Study: 2009-2020 update.

OBJECTIVES: We evaluated antibiotic resistance among intraocular isolates obtained from presumed endophthalmitis cases collected from 2009 through 2020 in the Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) study, the only ongoing nationwide surveillance study tracking in vitro resistance in ocular pathogens. METHODS: Presumed endophthalmitis isolates obtained from the aqueous humour and vitreous humour were collected from participating centres, and minimum inhibitory concentrations were determined and interpreted per Clinical and Laboratory Standards Institute methods and available breakpoints. RESULTS: A total of 307 presumed endophthalmitis isolates (aqueous humour, n = 88; vitreous humour, n = 219) were obtained from 43 clinical sites, including 188 coagulase-negative staphylococci (CoNS), 61 Staphylococcus aureus, 31 Streptococcus pneumoniae, 14 Pseudomonas aeruginosa, and 13 Haemophilus influenzae isolates. Of the CoNS isolates, 47.9% (90/188) were methicillin resistant, 58.0% (109/188) were azithromycin resistant, and 46.3% (87/188) were ciprofloxacin resistant. Of the S. aureus isolates, 45.9% (28/61) were methicillin resistant, 57.4% (35/61) were azithromycin resistant, and 44.3% (27/61) were ciprofloxacin resistant. Multidrug resistance (MDR; i.e., resistance to ≥3 antibiotic classes) was prevalent among staphylococci, particularly methicillin-resistant strains, of which >70% exhibited MDR. Resistance among S. pneumoniae isolates was notable for azithromycin and penicillin, each 38.7% (12/31), and for polymyxin B among P. aeruginosa 100.0% (14/14), whereas no resistance was observed for H. influenzae isolates to the antibiotics tested. CONCLUSION: In vitro antibiotic resistance was common among presumed endophthalmitis isolates collected in the ARMOR surveillance study. These data could inform antibiotic selection for infection prophylaxis and/or treatment of intraocular infections.

Classification of Presbyopia by Severity.

There are close to two billion individuals globally living with presbyopia. In spite of its ubiquitous and progressive nature, there is no widely accepted, formal guideline or consensus statement on the classification of presbyopia by degree of severity. A panel of leading eye care professionals representing both optometrists and ophthalmologists convened virtually to discuss and document their combined assessments from the body of literature and clinical practice expertise in this commentary. In light of emerging therapies, classifying presbyopia by mild, moderate, or advanced severity may help provide consistency of diagnosis among eye care providers and may aid in managing patient expectations with different treatment options.

Review of Loteprednol Etabonate 0.5%/Tobramycin 0.3% in the Treatment of Blepharokeratoconjunctivitis.

Use of a combination corticosteroid and antibiotic in a single formulation is common in the treatment of ocular inflammatory conditions for which corticosteroid therapy is indicated and there exists a risk of superficial bacterial infection. Loteprednol etabonate (LE) is a corticosteroid engineered to maintain potent anti-inflammatory activity while minimizing the risk of undesirable class effects of corticosteroids, such as elevated intraocular pressure and cataract. Tobramycin is a broad-spectrum aminoglycoside antibiotic that is considered generally safe and well tolerated. An ophthalmic suspension combining LE 0.5% and tobramycin 0.3% (LE/T) is approved in the US and several other countries. Use of a combination therapy increases convenience, which may promote patient adherence. A systematic literature review was conducted to examine the efficacy and safety of LE/T for ocular inflammatory conditions within the scope of its labeled indications. Results of published studies indicate that LE/T is effective in the treatment of blepharokeratoconjunctivitis in adults, with similar efficacy as dexamethasone 0.1%/tobramycin 0.3%, but is associated with a lower risk of clinically significant increases in intraocular pressure as demonstrated in both efficacy and safety studies and studies with healthy volunteers. Furthermore, studies in children with blepharitis or blepharoconjunctivitis indicate LE/T was well tolerated in this population, although efficacy vs vehicle was not demonstrated, potentially due to improvements in all groups overall and/or limited sample size. Separately, tobramycin demonstrated potent in vitro activity against most bacterial species associated with blepharitis. In conclusion, published data demonstrate the utility of LE/T for the treatment of the various clinical manifestations of blepharokeratoconjunctivitis in adults.

The corneal endothelium: clinical review of endothelial cell health and function.

The endothelial cell is a critical structure within the cornea and is responsible for maintaining corneal clarity through its pump function. Endothelial cells are lost over time naturally but can be injured medically, surgically, or as a part of various dystrophies. Monitoring of endothelial cells can be performed clinically or more formally with specular microscopy. In cases of significant compromise, endothelial cells can be transplanted by various endothelial keratoplasty techniques. The future pipeline is bright for possible endothelial cell regeneration and rehabilitation. This article reviews these topics in depth to provide a comprehensive look at the structure and function of the endothelial cell, etiologies of endothelial cell damage, detailed review of iatrogenic causes of endothelial cell loss, and management strategies.