Operating Room Waste Generated From Corneal and Conjunctival Surgeries.

PURPOSE: The purposes of this study were to bring awareness to the surgical waste generated from corneal and conjunctival surgeries and to compare those findings with the waste generated from cataract surgeries. METHODS: This was an observational prospective pilot cohort study at a tertiary corneal/anterior segment private practice. All waste related to cataract, cornea, and conjunctival surgical procedures (including anesthesia waste and corneal tissue storage) was weighed. The primary outcome was total waste generated while other outcomes included surgical setting (ambulatory surgical center, hospital, and minor operating room) and comparison of corneal/conjunctival surgeries with cataract surgery. RESULTS: Surgical waste data were collected from 119 surgeries (82 corneal/conjunctival surgeries and 37 cataract surgeries). Hospital surgeries produced more waste than ambulatory surgical center and minor operating room surgeries. Penetrating keratoplasty (2.22 kg, P = 0.483) and Descemet stripping only (2.11 kg, P = 0.326) procedures generated comparable mean waste with cataract surgery (2.07 kg) while endothelial keratoplasties produced more (P < 0.001, 0.002). (Deep) anterior lamellar keratoplasty results depended on the surgical setting. All conjunctival surgeries produced less waste than cataract surgery. CONCLUSIONS: In comparison with cataract surgery, keratoplasties overall produced comparable or more waste while conjunctival surgeries produced less waste. The surgical setting and type of anesthesia played a substantial role in the amount of waste generated. Assessing waste production from different ophthalmic surgeries may increase awareness of the negative environmental impact of surgical waste and promote practice or legal changes to improve environmental sustainability.

Efficacy of a Novel Water-Free Topical Cyclosporine 0.1 % Solution for Optimizing the Ocular Surface in Patients with Dry Eye and Cataract.

This is a pooled analysis from two phase III clinical trials investigating a water-free topical cyclosporine 0.1% for the treatment of moderate to severe dry eye. The analyses included 1162 patients: 35% with cataract, 20% with pseudophakia and 45% without cataract. Demographics or baseline characteristics were comparable across groups except for age and vision. The cyclosporine treated patients achieved large mean improvements from baseline by day 15: -3.7 in patients without cataract, -3.2 in patients with cataract and -3.1 in pseudophakic patients. These improvements were statistically significantly higher compared to the respective vehicle groups. In the cataract subgroup, 59% of patients treated with cyclosporine achieved ≥3 grade improvements in corneal staining score, as early as day 15. The magnitude of the effect and early onset of action make this novel cyclosporine solution a promising candidate for pre-operative management of ocular surface in patients undergoing cataract surgery.

Dual Accuracy-Quality-Driven Neural Network for Prediction Interval Generation.

Accurate uncertainty quantification is necessary to enhance the reliability of deep learning (DL) models in real-world applications. In the case of regression tasks, prediction intervals (PIs) should be provided along with the deterministic predictions of DL models. Such PIs are useful or "high-quality (HQ)" as long as they are sufficiently narrow and capture most of the probability density. In this article, we present a method to learn PIs for regression-based neural networks (NNs) automatically in addition to the conventional target predictions. In particular, we train two companion NNs: one that uses one output, the target estimate, and another that uses two outputs, the upper and lower bounds of the corresponding PI. Our main contribution is the design of a novel loss function for the PI-generation network that takes into account the output of the target-estimation network and has two optimization objectives: minimizing the mean PI width and ensuring the PI integrity using constraints that maximize the PI probability coverage implicitly. Furthermore, we introduce a self-adaptive coefficient that balances both objectives within the loss function, which alleviates the task of fine-tuning. Experiments using a synthetic dataset, eight benchmark datasets, and a real-world crop yield prediction dataset showed that our method was able to maintain a nominal probability coverage and produce significantly narrower PIs without detriment to its target estimation accuracy when compared to those PIs generated by three state-of-the-art neural-network-based methods. In other words, our method was shown to produce higher quality PIs.

A review of the first anti-evaporative prescription treatment for dry eye disease: perfluorohexyloctane ophthalmic solution.

Dry eye disease (DED) is one of the most common ocular surface disorders. All DED involves an imbalance between tear production and evaporation. Most cases of DED are driven by excessive evaporation, which is often associated with meibomian gland dysfunction (MGD). In evaporative DED, a deficient tear film lipid layer is believed to lead to increased tear evaporation, inflammation, and ocular surface damage. Most prescription treatments for DED address signs and symptoms by targeting tear production and/or inflammation, but they do not address excessive evaporation. Perfluorohexyloctane (PFHO) ophthalmic solution (MIEBO™; Bausch + Lomb) is a water-free, single-ingredient, preservative-free prescription eye drop that directly targets tear evaporation and is approved by the FDA to treat the signs and symptoms of DED. Results from preclinical studies indicate that PFHO has a high oxygen carrying capacity, may reduce friction on blinking, and spreads quickly over the tear film surface to form a monolayer that inhibits evaporation. These effects can lead to stabilization of the tear film to promote ocular surface healing. Further, PFHO was detected in tears for at least 6 hours in a rabbit pharmacokinetic study, and results indicate that it may improve lipid layer thickness and quality. In 2 pivotal phase 3 trials in patients with DED and clinical signs of MGD (GOBI [NCT04139798] and MOJAVE [NCT04567329]), treatment with PFHO consistently met primary efficacy end points related to DED signs and symptoms (total corneal fluorescein staining and eye dryness, respectively) and was well tolerated. Compared with use of hypotonic saline solution, instillation of PFHO led to significant improvements in signs and symptoms in as early as 2 weeks. In a long-term, open-label safety extension study, efficacy of PFHO was sustained over 12 months, and the safety profile was consistent with those of previous studies. Clinical trial results indicate that treatment with PFHO effectively and consistently reduces the signs and symptoms of DED.

Addressing excessive evaporation: an unmet need in dry eye disease.

Dry eye disease (DED) is a common condition in which tear film abnormalities result in a damaging cycle of tear hyperosmolarity, desiccating stress, inflammation, and ocular surface injury. In a healthy tear film, meibum produced by the meibomian glands forms a lipid layer that stabilizes the tear film and protects against aqueous tear evaporation. Excessive tear evaporation due to a deficient lipid layer is believed to be the most common cause of DED, and most evaporative DED is associated with meibomian gland dysfunction (MGD); this highlights the pathophysiologic importance of the dysfunctional tear lipid layer. Current treatments for DED may be used to supplement hyperosmolar aqueous tears, lubricate the ocular surface, increase meibum flow, decrease inflammation, promote tear production, or otherwise decrease clinical signs of ocular surface damage and/or improve symptoms. Until now, no prescription eye drop has directly addressed the excessive evaporation that occurs in most patients with DED. Perfluorohexyloctane (PFHO) ophthalmic solution (MIEBO™; Bausch + Lomb) is a preservative-free eye drop that has demonstrated the ability to form a long-lasting barrier that inhibits evaporation in preclinical studies. FDA approval of PFHO was based on results from 2 pivotal clinical trials (GOBI [NCT04139798] and MOJAVE [NCT04567329]) in patients with DED and clinical signs of MGD which demonstrated consistent improvements in both signs and symptoms of disease, with a safety profile similar to that of saline eye drops. PFHO is the first and only FDA-approved eye drop that directly targets tear evaporation in patients with DED, thereby promoting ocular surface healing and providing symptomatic relief.

TFOS Lifestyle: Impact of nutrition on the ocular surface.

Nutrients, required by human bodies to perform life-sustaining functions, are obtained from the diet. They are broadly classified into macronutrients (carbohydrates, lipids, and proteins), micronutrients (vitamins and minerals) and water. All nutrients serve as a source of energy, provide structural support to the body and/or regulate the chemical processes of the body. Food and drinks also consist of non-nutrients that may be beneficial (e.g., antioxidants) or harmful (e.g., dyes or preservatives added to processed foods) to the body and the ocular surface. There is also a complex interplay between systemic disorders and an individual's nutritional status. Changes in the gut microbiome may lead to alterations at the ocular surface. Poor nutrition may exacerbate select systemic conditions. Similarly, certain systemic conditions may affect the uptake, processing and distribution of nutrients by the body. These disorders may lead to deficiencies in micro- and macro-nutrients that are important in maintaining ocular surface health. Medications used to treat these conditions may also cause ocular surface changes. The prevalence of nutrition-related chronic diseases is climbing worldwide. This report sought to review the evidence supporting the impact of nutrition on the ocular surface, either directly or as a consequence of the chronic diseases that result. To address a key question, a systematic review investigated the effects of intentional food restriction on ocular surface health; of the 25 included studies, most investigated Ramadan fasting (56%), followed by bariatric surgery (16%), anorexia nervosa (16%), but none were judged to be of high quality, with no randomized-controlled trials.

Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial.

Importance: Dry eye disease (DED) is a common public health problem with significant impact on vision-related quality of life and well-being of patients. Medications with rapid onset of action and a good tolerability profile remain an unmet need. Objective: To assess efficacy, safety, and tolerability of a water-free cyclosporine ophthalmic solution, 0.1% (CyclASol [Novaliq GmbH]), applied twice daily in DED compared with vehicle. Design, Setting, and Participants: CyclASol for the Treatment of Signs and Symptoms of Dry Eye Disease (ESSENCE-2) was a phase 3, multicenter, randomized, double-masked, vehicle-controlled clinical study conducted from December 5, 2020, to October 8, 2021. Following a 14-day run-in period with an artificial tear administered 2 times per day, eligible participants were randomly assigned 1:1 to the treatment groups. Patients with moderate to severe DED were included in the study. Interventions: Cyclosporine solution vs vehicle administered 2 times per day for 29 days. Main Outcomes and Measures: The primary end points were changes from baseline in total corneal fluorescein staining (tCFS; 0-15 National Eye Institute scale) and in dryness score (0-100 visual analog scale) at day 29. Conjunctival staining, central corneal fluorescein staining, and tCFS responders were also assessed. Results: A total of 834 study participants were randomly assigned to cyclosporine (423 [50.7%]) or vehicle (411 [49.3%]) groups at 27 sites. Participants had a mean (SD) age of 57.1 (15.8) years, and 609 (73.0%) were female individuals. The majority of participants self-identified in the following race categories: 79 Asian (9.5 %), 108 Black (12.9%), and 635 White (76.1%). Participants treated with cyclosporine solution had greater improvement in tCFS (-4.0 grades) than the vehicle group (-3.6 grades) at day 29 (change [∆] = -0.4; 95% CI, -0.8 to 0; P = .03). The dryness score showed treatment benefits from baseline in both groups: -12.2 points for cyclosporine and -13.6 points for vehicle (∆ = 1.4; 95% CI, -1.8 to 4.6; P = .38). In the cyclosporine group, 293 participants (71.6%) achieved clinically meaningful reductions of 3 grades or higher in tCFS vs 236 (59.7%) in the vehicle group (∆ = 12.6%; 95% CI, 6.0%-19.3%; P < .001). These responders showed greater improvement in symptoms at day 29 including dryness (∆ = -4.6; 95% CI, -8.0 to -1.2; P = .007) and blurred vision (Δ = -3.5; 95% CI, -6.6 to -4.0; P = .03) compared with nonresponders. Conclusions and Relevance: The ESSENCE-2 trial confirmed that treatment with a water-free cyclosporine solution, 0.1%, results in early therapeutic effects on the ocular surface compared with vehicle. The responder analyses suggest that the effect is clinically meaningful in 71.6% of participants in the cyclosporine group. Trial Registration: ClinicalTrials.gov Identifier: NCT04523129.

Dry Eye Disease Associated with Meibomian Gland Dysfunction: Focus on Tear Film Characteristics and the Therapeutic Landscape.

Meibomian gland dysfunction (MGD) is highly prevalent and is the leading cause of evaporative dry eye disease (DED). MGD is characterized by a reduction in meibum secretion and/or a change in meibum composition that results in the disruption of the tear film lipid layer and an increase in the tear film evaporation rate. Excessive evaporation causes tear film instability, desiccation, tear hyperosmolarity, inflammation, and apoptosis of ocular surface cells, resulting in a continuous cycle of DED. The primary treatment goal for DED associated with MGD is to restore the tear film lipid layer and decrease evaporation, thereby reducing ocular signs and symptoms. The management of MGD includes home care options (eyelid hygiene, warming eye masks, ocular lubricants) and office-based treatments (manual expression, microblepharoexfoliation, thermal pulsation, intense pulsed light, intraductal probing). Topical ophthalmic prescription medications attempt to alter various factors that may contribute to DED (e.g., inflammation, bacterial growth, inadequate tear production). In this review, clinical evidence regarding available treatments and emerging therapies from randomized studies in patients with DED associated with MGD is summarized. Although some treatment modalities have been evaluated specifically for DED patients with MGD, large-scale randomized controlled trials are needed to confirm efficacy and safety in this patient population. Currently, there are no approved prescription pharmacologic treatments specifically indicated for DED associated with MGD, and those medications approved for the treatment of DED do not target the key driver of the disease (i.e., excessive evaporation). NOV03 (perfluorohexyloctane; under review with the US Food and Drug Administration) is the most advanced emerging therapy for DED associated with MGD and has demonstrated statistically significant improvements in both signs and symptoms in randomized controlled trials. Development of novel pharmacotherapies will improve therapeutic options and allow for a more individualized approach for patients with DED associated with MGD.

NOV03 for Signs and Symptoms of Dry Eye Disease Associated With Meibomian Gland Dysfunction: The Randomized Phase 3 MOJAVE Study.

PURPOSE: To evaluate the efficacy and safety of NOV03 (perfluorohexyloctane) ophthalmic drop for the treatment of signs and symptoms of dry eye disease (DED) associated with meibomian gland dysfunction (MGD). DESIGN: Randomized, double-masked, controlled trial. METHODS: Patients ≥18 years of age with a history of DED and signs of MGD were randomly assigned 1:1 to treatment with NOV03 or hypotonic saline (0.6%) 4 times daily for 8 weeks. The primary sign and symptom endpoints were change from baseline to week 8 in total corneal fluorescein staining (tCFS; National Eye Institute scale) and eye dryness score (0-100 visual analog scale), respectively. RESULTS: A total of 620 patients (NOV03, n = 311; saline, n = 309) were randomized and treated. Least-squares (LS) mean change from baseline to week 8 was statistically significantly greater for NOV03 compared with saline for both tCFS (-2.3 vs -1.1; LS mean treatment difference, -1.2 [95% confidence interval -1.7 to -0.8]; P < .001) and visual analog scale dryness score (-29.4 vs -19.2; LS mean treatment difference, -10.2 [95% CI -14.4 to -6.1]; P < .001), with statistically significant between-group differences observed as early as week 2. The incidence of ocular adverse events was similar for NOV03 (12.9%) and saline (12.3%). There were no serious adverse events and no adverse events leading to treatment discontinuation. CONCLUSIONS: In this randomized controlled trial of patients with DED associated with MGD, NOV03 significantly reduced both signs and symptoms of DED compared with hypotonic saline control. NOV03 was well tolerated, with an adverse event profile similar to that of saline.

Does Dry Eye Disease Severity Impact Efficacy of Varenicline Solution Nasal Spray on Sign and Symptom Treatment Outcomes?

SIGNIFICANCE: There is a clinical necessity for dry eye disease treatments that perform across a broad range of presenting patient severities. Varenicline solution nasal spray (VNS), a unique cholinergic agonist ocular surface-sparing nasal spray therapy, demonstrated significant improvement in both signs and symptoms of dry eye disease in subjects with mild, moderate, and severe symptoms as the clinical studies enrolled a more real-world patient population. PURPOSE: This study evaluated efficacy outcomes for VNS in patients with mild-moderate and severe dry eye disease. METHODS: An analysis of integrated data from two randomized clinical trials, ONSET-1 (NCT03636061) and ONSET-2 (NCT04036292) (vehicle control [VC], n = 294; VNS 0.03 mg, n = 308), was performed. Adults 22 years or older with dry eye disease, Ocular Surface Disease Index score of ≥23, corneal fluorescein staining score of ≥2 in ≥1 regions/≥4 all regions, and Schirmer Test Score (STS) of ≤10 mm (no restrictions on Eye Dryness Score [EDS]) were included in this study. Efficacy was evaluated using analysis of covariance among pre-specified subgroups of mild-moderate and severe baseline disease severity defined by STS (≤5 vs. >5) and EDS (<60 vs. ≥60). Consistency of effect was evaluated by interaction tests. RESULTS: No treatment-subgroup interactions were observed for all end points ( P > .05). The odds of achieving a ≥10-mm improvement in STS for VNS versus VC for patients with baseline STS ≤5 and >5 were 3.4(95% confidence interval, 2.0 to 5.6) and 2.3(1.3 to 4.0) and for EDS of <60 and ≥60 were 3.4(1.9 to 6.1) and 2.5(1.5 to 4.0). Least-squares mean treatment/VC differences in change from baseline in EDS for patients with baseline STS ≤5 or >5 were -7.4(95% confidence interval, -12.5 to -2.4) and -2.8(-8.7 to 3.1); EDS of <60 and ≥60 were -2.9(-8.3 to 2.5) and -8.1(-13.6 to -2.6). CONCLUSIONS: Compared with VC, VNS improved tear production and patient-reported symptoms in patients with dry eye disease, demonstrating consistency of effect regardless of initial presenting severity.

Improved Yield Prediction of Winter Wheat Using a Novel Two-Dimensional Deep Regression Neural Network Trained via Remote Sensing.

In recent years, the use of remotely sensed and on-ground observations of crop fields, in conjunction with machine learning techniques, has led to highly accurate crop yield estimations. In this work, we propose to further improve the yield prediction task by using Convolutional Neural Networks (CNNs) given their unique ability to exploit the spatial information of small regions of the field. We present a novel CNN architecture called Hyper3DNetReg that takes in a multi-channel input raster and, unlike previous approaches, outputs a two-dimensional raster, where each output pixel represents the predicted yield value of the corresponding input pixel. Our proposed method then generates a yield prediction map by aggregating the overlapping yield prediction patches obtained throughout the field. Our data consist of a set of eight rasterized remotely-sensed features: nitrogen rate applied, precipitation, slope, elevation, topographic position index (TPI), aspect, and two radar backscatter coefficients acquired from the Sentinel-1 satellites. We use data collected during the early stage of the winter wheat growing season (March) to predict yield values during the harvest season (August). We present leave-one-out cross-validation experiments for rain-fed winter wheat over four fields and show that our proposed methodology produces better predictions than five compared methods, including Bayesian multiple linear regression, standard multiple linear regression, random forest, an ensemble of feedforward networks using AdaBoost, a stacked autoencoder, and two other CNN architectures.

Phialophora chinensis fungal keratitis: An initial case report and species identification.

Purpose: To report the initial case of microbial keratitis caused by Phialophora chinensis, a rare cause of fungal keratitis. Observations: A 66-year-old gentleman with a complex right eye (OD) ocular history including herpes simplex virus infectious epithelial keratitis with subsequent neurotrophic keratopathy, and prior combined Candida albicans and parapsilosis fungal keratitis presented with pain OD in the absence of an antecedent trauma. The patient was found to have a filamentous fungal keratitis, which was subsequently cultured and identified as Phialophora chinensis by the laboratory. Despite topical and oral antifungal treatment based on sensitivities determined by the lab, the patient ultimately required intrastromal and subconjunctival antifungal injections, corneal crosslinking, and superficial keratectomy with amniotic membrane to clinically improve. The fungal keratitis recurred twice, with each occurrence rapidly progressing to corneal perforation. Months after the second penetrating keratoplasty, the patient's mental status declined due to multiorgan failure. An occult pulmonary malignancy was discovered during this hospital stay, and the patient was lost to follow-up after entering hospice. Conclusions and Importance: We report a unique case of fungal keratitis caused by Phialophora chinensis and the subsequent management, including both medical and surgical interventions. Despite a multimodal treatment regimen, this case demonstrates the recalcitrant and potentially recurrent nature of fungal keratitis caused by P. chinensis.

Comparison of Persistent Epithelial Defect Treatment With Sutureless Cryopreserved and Dehydrated Amniotic Membrane.

PURPOSE: To compare cryopreserved sutureless amniotic membrane (C-SAM) and dehydrated SAM (D-SAM) outpatient treatment outcomes for persistent epithelial defects (PEDs), analyze risk factors for treatment failure, and identify adverse events. DESIGN: Retrospective, interventional comparative clinical study. METHODS: This study was a multicenter retrospective interventional cohort from 2 tertiary corneal referral practices from 2016 to 2020. The inclusion criteria were as follows: (1) PEDs treated (2) outpatient with (3) either C-SAM or D-SAM. PEDs were defined as epithelial defects present for ≥7 days after failing prior conservative therapy. The primary outcome measure was the resolution or improvement of a PED. The secondary outcomes included analysis of treatment failures and identification of adverse events. A total of 220 PEDs from 204 eyes (197 patients) treated with either C-SAM or D-SAM met the inclusion criteria. RESULTS: A total of 100 PEDs (45.5%) resolved after single amniotic membrane administration, 46.5% (59 of 127) in the C-SAM group and 44.1% (41 of 93) in the D-SAM group (P = .727). Forty-nine PEDs neither improved nor resolved without a significant difference between the C-SAM (21.3%) and D-SAM groups (23.7%, P = .673). There was no statistically significant difference for PED resolution, PED improvement, PEDs that did not resolve/improve, or those requiring surgery between the 2 groups for initial SAM. CONCLUSIONS: C-SAM and D-SAM were both effective for treating PEDs with comparable outcomes for resolution, improvement, and need for additional surgical intervention. Specific differences in adverse events may help dictate clinical use. Inflammatory disease was a risk factor for nonresolution of all PEDs.

Dry eye disease: identification and therapeutic strategies for primary care clinicians and clinical specialists.

Dry eye disease (DED) is a multifactorial disorder characterized by loss of tear film homeostasis with an estimated worldwide prevalence of 5% to 50%. In DED, dysfunction of the ocular structures that create and regulate the tear film components-including the lacrimal glands, meibomian glands, cornea, and conjunctiva-causes a qualitative and/or quantitative tear deficiency with resultant tear film instability and hyperosmolarity. This initiates a vicious cycle of ocular surface inflammation and damage that may ultimately impair the quality of life and vision of affected patients. Many factors can contribute to the development of DED, including ocular and systemic diseases, topical and systemic medications, and environmental conditions. Because DED is a chronic disorder, treatment is most often long term and may utilize both pharmacologic and nonpharmacologic interventions to address all etiologic components. The long-term management of DED can be challenging and most often should involve eye care specialist referral. However, primary care clinicians (PCCs) are often the first points of contact for patients with DED and importantly provide initial diagnosis and preliminary patient education about the disease process. Consideration of DED is also vital for the practice of various specialties due to the large number of comorbidities and medications that can contribute to DED pathogenesis and progression. Therefore, it is important that PCCs and clinical specialists be aware of the etiology of DED and its available therapeutic options. This manuscript provides an overview of DED pathophysiology and treatment and discusses specific considerations regarding DED management for PCCs and clinical specialists.Key messagesSuccessful management of dry eye disease often requires the use of various pharmacologic and/or nonpharmacologic therapies, as well as environmental and lifestyle modifications, to mitigate the underlying etiologies and restore tear film homeostasis.Primary care clinicians play an essential role in dry eye disease management by establishing a diagnosis, educating patients about the disorder, and providing referrals to eye care specialists for initiation of specialized treatment and long-term follow-up.Primary care clinicians and clinical specialists should consider prescribing medications with fewer ocular surface effects whenever possible in patients at risk for or with existing dry eye disease.

A Comparison of Spinal Robotic Systems and Pedicle Screw Accuracy Rates: Review of Literature and Meta-Analysis.

Introduction The motivation to improve accuracy and reduce complication rates in spinal surgery has driven great advancements in robotic surgical systems, with the primary difference between the newer generation and older generation models being the presence of an optical camera and multijointed arm. This study compares accuracy and complication rates of pedicle screw placement in older versus newer generation robotic systems reported in the literature. Methods We performed a systemic review and meta-analysis describing outcomes of pedicle screw placement with robotic spine surgery. We assessed the robustness of these findings by quantifying levels of cross-study heterogeneity and publication bias. Finally, we performed meta-regression to test for associations between pedicle screw accuracy and older versus newer generation robotic spine system usage. Results Average pedicle screw placement accuracy rates for old and new generation robotic platforms were 97 and 99%, respectively. Use of new generation robots was significantly associated with improved pedicle screw placement accuracy ( p = 0.03). Conclusion Accuracy of pedicle screw placement was high across all generations of robotic surgical systems. However, newer generation robots were shown to be significantly associated with accurate pedicle screw placement, showing the benefits of upgrading robotic systems with a real-time optical camera and multijointed arm.

Phase 2, Randomized, Open-Label Parallel-Group Study of Two Dosing Regimens of Netarsudil for the Treatment of Corneal Edema Due to Fuchs Corneal Dystrophy.

Background: This phase 2 study evaluated the therapeutic potential of netarsudil to reduce corneal edema and to improve vision in patients with Fuchs corneal dystrophy (FCD). Methods: Patients (N = 40) with baseline central corneal thickness (CCT) of ≥600 µm and best-corrected visual acuity (BCVA) of 70-20 letters (20/40-20/400 Snellen equivalent) were randomized 1:1 to receive netarsudil once a day (QD) or twice a day (BID) for 8 weeks. Primary endpoint was mean CCT change from baseline at week 4. Results: Netarsudil QD and BID significantly reduced CCT at week 4 [mean change (standard error of mean), 28.4 (7.99) µm, P = 0.0021; and 20.1 (8.75) µm, P = 0.0335, respectively]. Five (12.5%) patients achieved complete resolution of corneal edema at week 4. BCVA improved by 3.2 (2.76) letters with QD and 1.5 (2.84) letters with BID, and 10 (25%) patients [5 with QD (P = 0.0078) and 5 with BID (P = 0.0096)] gained ≥10 letters at week 4. Improvements in CCT and vision were observed at week 2 and persisted at week 8, without significant differences between the 2 doses at any time point. Netarsudil QD significantly improved visual acuity and glare factor scores on the Visual Function and Corneal Health Status (V-FUCHS) questionnaire at weeks 4 and 8 (mean change, -0.4 to -0.3; P ≤ 0.0200). Netarsudil was well tolerated. Reticular edema developed in one (2.5%) patient with BID, which resolved with treatment discontinuation. Conclusions: Netarsudil QD led to significant reductions in corneal edema as well as improvements in vision and patient-reported symptoms of glare and visual impairment in patients with FCD. Clinical Trial Registration Number: NCT04498169.

Supraorbital Keyhole Craniotomy for Clipping Cerebral Aneurysms: A Systematic Review and Meta-Analysis.

BACKGROUND: Open cerebrovascular surgery remains an irreplaceable tool in the neurosurgeon's armamentarium for cerebral aneurysms. Among open approaches, the supraorbital keyhole approach provides a novel approach with less soft tissue dissection and cortical exposure compared with the traditional pterional approach. OBJECTIVE: To perform a descriptive synthesis of the literature on cerebral aneurysms approached surgically via the supraorbital keyhole approach. METHODS: Following PRISMA guidelines, we performed a systematic literature review of PubMed, Scopus, and Web of Science. Patient demographic data, aneurysm characteristics, Hunt and Hess score, clipping rate, operative time, postoperative neurologic status, length of stay, and follow-up were extracted. We then performed a meta-analysis to obtain pooled estimates of these metrics across studies, including assessments for cross-study heterogeneity and publication bias. RESULTS: Under a random-effects estimate, mean intraoperative rupture rate was 6.0%. Clipping rate was 99% under a pooled fixed estimate. Significant publication bias was found within studies for aneurysm clipping rate. Forest plot analysis showed an average clinical outcome of 93% of a modified Rankin Scale score from 0 to 2 or Glasgow Outcome Scale score of IV or V at postoperative follow-up. CONCLUSIONS: Aneurysm treatment is highly heterogeneous within the literature. The supraorbital keyhole approach is an effective strategy for aneurysm treatment.

Gut Microbiome and Its Influence On Ocular Surface and Ocular Surface Diseases.

ABSTRACT: The gut microbiome plays a substantial immunologic and pathophysiologic role in maintaining the health of the host, and dysregulation of this dynamic ecosystem has been associated with several inflammatory conditions. Many studies have explored the influence of gut microbiota on the ocular surface and whether gut microbiota impact the pathophysiology of ophthalmic conditions. These findings have highlighted the advantages of enhancing gut microbes through probiotics, prebiotics, diet, vitamin supplementations, and fecal microbial transplant in clinical practice. The purpose of this review article was to provide an up-to-date overview of the knowledge on this topic. Further exploration of this area of research is important to help guide new therapeutic targets to develop treatment and prevention of certain ocular surface diseases.

Selective Pharmacologic Therapies for Dry Eye Disease Treatment: Efficacy, Tolerability, and Safety Data Review from Preclinical Studies and Pivotal Trials.

Keratoconjunctivitis sicca, also known as dry eye disease (DED), is a prevalent, multifactorial disease associated with compromised ocular lubrication, ocular surface inflammation and damage, and ocular symptoms. Several anti-inflammatory, topical ophthalmic therapies are available to treat clinical signs and symptoms of DED in the USA and Europe. Cyclosporine A (CsA)-based formulations include an ophthalmic emulsion of 0.05% CsA (CsA 0.05%), a cationic emulsion (CE) of CsA 0.1% (CsA CE), and an aqueous nanomicellar formulation of 0.09% CsA (OTX-101). Lifitegrast is a 5% ophthalmic solution of a lymphocyte function-associated antigen 1 antagonist that is believed to target T cell activation and recruitment to inhibit ocular inflammation. Here we provide a comprehensive review summarising preclinical studies and pivotal trial data for these treatments to provide a complete understanding of their efficacy and safety profile. Overall, data in the evaluated studies show a favourable risk-benefit profile for the use of targeted topical anti-inflammatory pharmacologic treatments in patients with DED. Pivotal trials for CsA 0.05%, CsA CE, OTX-101, and lifitegrast clearly demonstrate treatment efficacy compared to vehicle across treatments with no serious ocular treatment-emergent adverse events (TEAEs). Patients using ophthalmic treatments reported ocular TEAEs more frequently than those treated with vehicle; however, relatively few TEAEs led to treatment discontinuation. The specific signs and symptoms of DED that improve with treatment vary with the treatment prescribed. Long-term and direct comparative studies between treatments are needed to further understand treatment differences in efficacy and safety profiles.