The Effectiveness and Safety of a Novel Crosslinked Hyaluronate Canalicular Gel Occlusive Device for Dry Eye.

PURPOSE: Evaluate effectiveness and safety of a crosslinked hyaluronate (HA) canalicular filler (Lacrifill Canalicular Gel) compared to a commercially available hydrogel canalicular plug (Form Fit). SETTING: 5 sites in United States. DESIGN: Prospective, multicenter, controlled, double-masked, randomized 2:1 (filler:plug). METHODS: Adults (≥22 years) with Schirmer test (with anesthesia) ≤10 mm/5 minutes, presence of corneal staining, ocular surface disease index (OSDI) of ≥23 with ≤3 responses of "not applicable," patent lacrimal drainage system, and bilateral best-corrected distance visual acuity of 20/40 or better. Filler or plugs were instilled bilaterally in the inferior canaliculi. Primary effectiveness endpoint was non-inferiority of the mean within subject change from baseline to Month 3 in Schirmer score for patients receiving filler compared to plugs. The key secondary effectiveness endpoint was non-inferiority of the proportion of patients with filler achieving improvement from baseline to Month 3 in OSDI by a minimal clinically important difference (MCID). Additional endpoints included the mean change from baseline to 3 and 6 months in tear meniscus height, OSDI, corneal staining, tear break-up time, and safety. RESULTS: 157 patients were randomized; 99 patients with crosslinked HA filler and 52 patients with hydrogel plugs completed the study. Filler was non-inferior to plugs in the mean Schirmer score change from baseline and in the proportion of patients achieving a clinically important improvement in OSDI. CONCLUSIONS: Crosslinked HA filler is a safe, well-tolerated, and effective method to treat dry eye. Clinically and statistically significant improvements in signs and symptoms of dry eye were sustained through 6 months.

Early Real-World Patient and Staff Experience with an Intracanalicular Dexamethasone Insert.

Purpose: To evaluate both the early experience of real-world patients treated with dexamethasone ophthalmic insert (0.4 mg; DEXTENZA®), hereafter referred to as DEX, after cataract surgery as well as staff/practice integration of DEX relative to eyedrops. Patients and Methods: This was a cross-sectional survey study of 23 cataract practices in the United States. Respondents were patients and practice staff who had experience with DEX following cataract surgery. Both patients and practice staff completed an online survey. Descriptive statistics summarized the survey responses to portray the experience of the respondents. Results: Surveys were completed by 62 patients and 19 practice staff. Almost all patients (93%) were satisfied or extremely satisfied with DEX. Patients highly preferred DEX (93%) to topical steroid drops (7%) based on past experiences with topical steroid drops. Most practice staff (95%) were satisfied or highly satisfied with DEX, reporting a 45% reduction in time spent educating patients on postoperative drop use and a 46% decrease in time spent addressing calls from pharmacies regarding postoperative medications. Conclusion: Incorporating the DEX insert into clinical practice in cataract surgery practices can improve patient adherence, while potentially providing significant savings to practices in terms of time spent educating patients and responding to patient and pharmacy call-backs.

Considerations for the Identification and Management of Geographic Atrophy: Recommendations from an Expert Panel.

Newly approved treatments for patients with geographic atrophy are changing the treatment paradigm, highlighting the need for eye care providers (ECPs) to have a set of recommendations on how to best manage GA patients. Here, we outline how to identify various stages of age-related macular degeneration including geographic atrophy (GA) by examining optimal management scenarios implicating various ECPs and reviewing treatment considerations for patients with GA. Early identification of GA will lead to optimal patient outcomes, while a standardized management scenario will reduce clinical burden among ECPs treating patients with GA.

Long-Term Outcomes of 6-Week Treatment of Lotilaner Ophthalmic Solution, 0.25%, for Demodex Blepharitis: A Noninterventional Extension Study.

PURPOSE: The aim of this study was to evaluate the long-term outcomes of lotilaner ophthalmic solution, 0.25%, in the treatment of Demodex blepharitis. METHODS: This observational, extension study included patients with Demodex blepharitis (N = 239) who completed the Saturn-1 study and presented for the day 180 visit. All participants were assessed at days 180 and 365 after the initiation of 6-week treatment with the study drug or its vehicle. RESULTS: The proportion of patients with 0 to 2 collarettes (grade 0) was significantly higher in the study group (N = 128 patients) than in the control group (N = 111 patients) (39.8% vs. 2.7% at day 180 and 23.5% vs. 2.9% at day 365; P < 0.0001). Similarly, the proportion of patients with ≤10 collarettes (collarette grade 0-1) in the study group was significantly higher than in the control group (70.3% vs. 18.0% at day 180 and 62.6% vs. 21.9% at day 365; P < 0.0001). In the study group, erythema continued to improve even after completion of the 6-week lotilaner treatment. No serious ocular adverse events were observed in the study group, and there was 1 treatment-related ocular adverse event in the study group, which was considered mild. CONCLUSIONS: After 6-week treatment with lotilaner ophthalmic solution, 0.25%, for Demodex blepharitis, no long-term concerns were observed during 1 year of follow-up. A high proportion of patients with 0 to 2 collarettes (grade 0) or ≤10 collarettes (collarette grade of 0 or 1) was observed throughout 1 year of follow-up, indicating that the efficacy of lotilaner ophthalmic solution, 0.25%, against Demodex blepharitis may last well after completion of therapy.

Glaucoma and Dry Eye Disease: Opportunity to Assess and Treat.

Dry eye disease (DED) has been found to occur at a higher prevalence in individuals with glaucoma than in individuals without glaucoma. The relationship between glaucoma and DED may be, in part, a result of glaucoma therapy. Greater number of antiglaucoma medications used and greater number of antiglaucoma eyedrops instilled per day have been associated with ocular surface disease in patients with glaucoma. Use of antiglaucoma medication has also been associated with higher levels of ocular surface inflammatory markers and ocular surface alterations. There is evidence to suggest that antiglaucoma medications with preservatives and, to some extent, antiglaucoma medication formulations without preservatives may contribute to ocular surface signs and symptoms. Trabeculectomy for glaucoma has also been associated with ocular surface signs related to DED; however, there may be benefits of trabeculectomy and other procedures for glaucoma due to reduced use of antiglaucoma medications. Patients with glaucoma with ocular surface disease have been found to have greater ocular surface symptoms, poorer vision-related quality of life, and poorer antiglaucoma medication adherence compared with patients with glaucoma without ocular surface disease. Because of the potential negative impact of DED on patients with glaucoma, patients with glaucoma may benefit from evaluation for DED. Management of DED in patients with glaucoma may include modifications to antiglaucoma medications and use of treatments for DED.

Geographic Atrophy Management Consensus (GA-MAC): a Delphi panel study on identification, diagnosis and treatment.

BACKGROUND/AIMS: With a paradigm shift in geographic atrophy (GA) treatments now available, establishing consensus on the identification and diagnosis of the disease along with considerations for management of patients with GA will assist eye care professionals (ECP) in their day-to-day practices, leading to improved patient outcomes. METHODS: A modified Delphi panel process (Geographic Atrophy Management Consensus) consisting of three total surveys and one virtual live meeting held between survey 2 and survey 3. Data were collected from July to October 2022. Participants included expert members of the eye care community that have demonstrated outstanding leadership among peers: a steering committee with three ECPs and a 15-member panel divided between five optometrists, five comprehensive ophthalmologists and five retina specialists. Consensus on statements related to the management of patients with GA was calculated using the RAND/UCLA Appropriateness Method. RESULTS: At the conclusion of the third survey, consensus was reached on 91% of the 77 statements. Critical consensus topics include: (1) optical coherence tomography as the favoured method to diagnose and monitor GA, (2) preferred practice patterns regarding referral of patients to retina specialists and (3) treatment criteria given the advent of emerging therapeutics for GA. CONCLUSIONS: Generating awareness of early signs of disease development, progression and identifying the best tools to evaluate GA establishes ideal management and referral strategies. Given the paradigm shift in GA management driven by approved therapies, coupled with the fact that the disease is progressive resulting in devastating vision loss, these strategies are critical to ensure best overall outcomes.

Does Menopausal Status Affect Dry Eye Disease Treatment Outcomes with OC-01 (Varenicline Solution) Nasal Spray? A Post Hoc Analysis of ONSET-1 and ONSET-2 Clinical Trials.

INTRODUCTION: This study sought to compare the efficacy of OC-01 (varenicline solution) nasal spray for treatment of dry eye disease (DED) in postmenopausal women (PM+) versus women who were not postmenopausal (PM-). METHODS: This was a post hoc subgroup analysis of data integrated from two prior randomized controlled clinical trials, ONSET-1 and ONSET-2. Women randomized to treatment with OC-01 (varenicline solution) nasal spray 0.03 mg or vehicle control (VC) whose self-reported menopausal status (PM+ versus PM-) was known were included. Outcomes included the treatment difference (the OC-01 [varenicline solution] nasal spray change from baseline [CFB] minus VC CFB) in Schirmer test score (STS, mm) with anesthesia and the eye dryness score (EDS) measured on a 100-mm visual analog scale (0 = no discomfort, 100 = maximal discomfort). Least-squares mean treatment differences were derived from analysis of covariance (ANCOVA) models. RESULTS: Overall, 449 female participants in the ONSET-1 and ONSET-2 trials randomized to the OC-01 (varenicline solution) nasal spray 0.03 mg or VC groups were included in this analysis. The treatment-menopausal status interaction terms in the STS and EDS ANCOVA and logistic regression models were not statistically significant (p > 0.05), indicating consistency of treatment effect between the PM- and PM+ groups. The treatment difference in STS was similar in the PM- and PM+ groups (6.7 and 5.5 mm, respectively). The treatment difference in EDS was similar in the PM- and PM+ groups (- 5.5 and - 4.1, respectively). CONCLUSIONS: OC-01 (varenicline solution) nasal spray demonstrated similar efficacy in promoting natural tear production and improving symptoms in both PM- and PM+ groups. As menopausal-related hormonal changes may be associated with more severe DED, these results may support OC-01 (varenicline solution) nasal spray as an effective treatment for DED in women regardless of presenting menopausal status. TRIAL REGISTRATION: Post hoc subgroup analysis of data integrated from ONSET-1 (ClinicalTrials.gov identifier NCT03636061) and ONSET-2 (ClinicalTrials.gov identifier NCT04036292).

Contractual considerations in the private equity era.

Private equity (PE) has grown rapidly in medicine. The reintroduction of PE in ophthalmology has necessitated a greater understanding of the potential contractual relationships with PE firms from both a practice owner and an employee physician perspective. There are contractual obligations that need to be met as PE agreements are designed to ensure clear investment patterns and abide by legal mandates. A practice owner entering into a PE contract needs to consider how the practice is being valued, what their obligations are to the PE entity after the sale has been completed to attain full compensation and understand their new role at the practice. On the other hand, employee ophthalmologists must carefully evaluate the compensation package being offered in terms of the type of equity, vesting of shares, obligations to the PE firm under the agreement such as a noncompete clause, and what occurs under a subsequent sale of the practice. Overall, contractual considerations in the private equity era need to be carefully evaluated in order to ensure the agreement is in the best interest for the clinician, practice, and their patients.

Real-World Experience with Intracapsular Administration of Dexamethasone Intraocular Suspension 9% for Control of Postoperative Inflammation.

Corticosteroids and non-steroidal anti-inflammatory drugs are commonly used prophylactically to control inflammation after ocular surgery. When prescribed as eye drops, as has been longstanding tradition, anti-inflammatory success is out of surgeons' hands, dependent on patient compliance and proper instillation technique. Sustained-release, intraoperatively administered anti-inflammatory drugs are emerging as another option. DEXYCU (dexamethasone intraocular suspension) 9% is the first and only intraocular corticosteroid FDA-approved for postoperative inflammation, whose sustained-release formulation provides a high initial release of drug, followed by a gradual tapering. Administration of the drug directly into the capsular bag following cataract surgery enables reliable placement proximal to target tissues, ensuring surgeon control and visibility of delivery, safety, and efficiency. This technique also minimizes contact with metabolically active tissues such as the corneal endothelium, iris, and ciliary body. In this paper, we review the available literature on dexamethasone intraocular suspension and summarize surgeons' consensus on best practices for intracapsular administration.

Expert consensus on the identification, diagnosis, and treatment of neurotrophic keratopathy.

BACKGROUND: Neurotrophic keratopathy (NK) is a relatively uncommon, underdiagnosed degenerative corneal disease that is caused by damage to the ophthalmic branch of the trigeminal nerve by conditions such as herpes simplex or zoster keratitis, intracranial space-occupying lesions, diabetes, or neurosurgical procedures. Over time, epithelial breakdown, corneal ulceration, corneal melting (thinning), perforation, and loss of vision may occur. The best opportunity to reverse ocular surface damage is in the earliest stage of NK. However, patients typically experience few symptoms and diagnosis is often delayed. Increased awareness of the causes of NK, consensus on when and how to screen for NK, and recommendations for how to treat NK are needed. METHODS: An 11-member expert panel used a validated methodology (a RAND/UCLA modified Delphi panel) to develop consensus on when to screen for and how best to diagnose and treat NK. Clinicians reviewed literature on the diagnosis and management of NK then rated a detailed set of 735 scenarios. In 646 scenarios, panelists rated whether a test of corneal sensitivity was warranted; in 20 scenarios, they considered the adequacy of specific tests and examinations to diagnose and stage NK; and in 69 scenarios, they rated the appropriateness of treatments for NK. Panelist ratings were used to develop clinical recommendations. RESULTS: There was agreement on 94% of scenarios. Based on this consensus, we present distinct circumstances when we strongly recommend or may consider a test for corneal sensitivity. We also present recommendations on the diagnostic tests to be performed in patients in whom NK is suspected and treatment options for NK. CONCLUSIONS: These expert recommendations should be validated with clinical data. The recommendations represent the consensus of experts, are informed by published literature and experience, and may improve outcomes by helping improve diagnosis and treatment of patients with NK.

Understanding the Dual Dilemma of Dry Eye and Glaucoma: An International Review.

Glaucoma-related ocular surface disease (G-OSD) is a significant, yet often underdiagnosed, ocular co-morbidity affecting 40% to 59% of glaucoma patients worldwide. Although the use of topical glaucoma medications represents a proven strategy to control the untoward effects of high intraocular pressure, this treatment can profoundly disrupt the homeostasis of the tear film. The cumulative effect of medications, preservatives, and excipients alter underlying cellular structures which results in tear film abnormalities and instability of the ocular surface. Furthermore, these chronic inflammatory changes have been shown to impact efficacy of glaucoma treatment, patient compliance with therapy and overall quality of life. The pathogenesis of G-OSD is multifactorial and involves a vicious self-perpetuating cycle of inflammatory cytokines and proteins. The diagnosis of such disease is based on similar tests used in assessing traditional dry eye, taking into consideration findings specific to this patient population. The hallmark of treatment for these patients is to minimize the ocular surface inflammatory response by choosing glaucoma therapies that spare the ocular surface such as preservative free formulations and initiating dry eye treatment early in the course of care. In summary, glaucoma affects millions of patients around the world and chronic use of topical glaucoma medications may negatively impact the patient's ocular surface, symptoms, and vision. Understanding the pathogenesis of G-OSD, recognizing its risk factors and incorporating diagnostic and therapeutic strategies that restore and maintain ocular surface homeostasis will result in improved care for our patients.

Vitreous and Aqueous Penetration of Orally Administered Trimethoprim-Sulfamethoxazole Combination in Humans.

PURPOSE: To determine the penetration of orally administered trimethoprim (TMP)-sulfamethoxazole (SMX) into the aqueous and vitreous cavity of noninflamed human eyes. METHODS: Nine adult patients undergoing cataract surgery and 10 adult patients undergoing pars plana vitrectomy were given 3 doses of oral TMP-SMX every 12 hours before the surgery. Aqueous and blood samples were collected from patients undergoing cataract surgery; vitreous and blood samples were collected from patients undergoing vitrectomy. The levels of TMP and SMX were analyzed using high-performance liquid chromatography and were compared with the mean minimum inhibitory concentrations (MIC) of potential ocular pathogens. RESULTS: TMP-SMX was present in all samples. Among eyes undergoing cataract surgery, the mean concentrations of TMP in aqueous and blood were 0.341 ± 0.141 µg/mL (mean ± SD) and 1.501 ± 0.433 µg/mL and of SMX were 5.259 ± 0.929 µg/mL and 11.835 ± 2.100 µg/mL, respectively. Among eyes undergoing vitrectomy, the mean concentrations of TMP in vitreous and blood were 1.864 ± 0.807 µg/mL and 4.591 ± 2.979 µg/mL and of SMX were 5.910 ± 2.705 µg/mL and 39.289 ± 15.469 µg/mL, respectively. MIC levels were achieved against many bacterial pathogens, including methicillin-resistant Staphylococcus aureus. CONCLUSIONS: TMP-SMX penetrates both the aqueous and vitreous cavities when given orally. The components reach therapeutic inhibitory concentrations in the ocular cavity against many potential pathogens.

An adaptable HPLC method for the analysis of frequently used antibiotics in ocular samples.

Four different antibiotics, delivered individually to rabbit eyes via hydrophilic intraocular lenses soaked in the drug solution prior to implantation, were measured in aqueous and vitreous humor samples from the eyes. To meet this analytical need, we developed a sensitive, high performance liquid chromatographic (HPLC) method for measuring the concentrations of moxifloxacin, gatifloxacin, linezolid, and cefuroxime in the ocular tissue. Separations were carried out on a LichroSpher RP-18 column, maintained at room temperature. The fluoroquinolones were eluted with a mobile phase consisting of 20% acetonitrile, in 0.1% trifluoroacetic acid (pH 3.0) with 30 mM tetrabutylammonium chloride. Linezolid and cefuroxime were eluted with 25% acetonitrile in 25 mM Na acetate buffer, pH 5.0. All elutions were isocratic. With ultraviolet detection, the lower limit of quantitation (LLOQ) for these compounds approached 1 ng (on-column injection). By using fluorescence detection, the LLOQ for the fluoroquinolones improved to 200 pg. The overall accuracy of the method was >or=90%. With minor modifications, the method was optimized for each of the agents, and the resulting analytical sensitivity made the method suitable for clinical investigations of the ocular penetration of these drugs.

Polymicrobial keratitis: Acanthamoeba and infectious crystalline keratopathy.

PURPOSE: To report the early presentation, cause, and successful medical management of combined Acanthamoeba keratitis (AK) and infectious crystalline keratopathy (ICK). DESIGN: Interventional case series. METHODS: Retrospective review of 111 AK patients diagnosed and managed at the University of Illinois Eye and Ear Infirmary between June 1, 2003 and November 30, 2008 for an additional diagnosis of infectious keratitis. RESULTS: Of 5 AK patients with microbiologic evidence of an additional bacterial keratitis during their active AK treatment, concomitant ICK developed in 3 patients. All patients were examined within 3 weeks of their AK diagnosis and were found to have characteristic signs and symptoms consistent with ICK. Bacterial culture results at the time of AK diagnosis were negative in 2 patients, but subsequent culture results were positive for Streptococcus oralis. Initial culture results demonstrated light growth of methicillin-sensitive Staphylococcus aureus in the remaining patient, who had received partial antibiotic treatment. Topical corticosteroids were used before diagnosis in 2 patients and were in use in only 1 patient after AK diagnosis. All infections resolved with medical therapy alone. One patient later required penetrating keratoplasty for visual rehabilitation. CONCLUSIONS: In patients with AK, ICK can develop early and without either the use of corticosteroids or a preexisting epithelial defect, inconsistent with previously suggested mechanisms and major risk factors for secondary infection. Combined AK and ICK may exhibit increased pathogenicity with the onset of severe, often new, pain and acceleration of localized tissue loss and resultant scarring. Although early recognition and aggressive medical treatment were successful in resolving the combined infections in our cases, Acanthamoeba coinfection, and perhaps endosymbiosis, should be considered in the evaluation and clinical management of AK, especially in those cases progressing atypically. Further research is needed to understand the precise mechanism of the introduction of coinfectious pathogens and their role in the pathogenicity of AK.