Treatment Option For Glaucoma Research Articles

Perceptions and Misconceptions About Eye Disease Treatment: A Cross-Sectional Study From Jazan, Saudi Arabia.

Eye diseases such as cataracts and glaucoma significantly contribute to vision impairment and blindness worldwide. While cataracts are the leading cause of preventable blindness, glaucoma, often referred to as the "silent thief of sight", can lead to irreversible vision loss if untreated. Despite their prevalence, awareness and understanding of these conditions remain low, particularly in regions like Saudi Arabia, where demographic changes and rising diabetes rates exacerbate the burden of eye diseases. This study aims to assess the knowledge and perceptions of cataracts and glaucoma among residents of Jazan to identify gaps and inform public health interventions. A cross-sectional online survey was conducted among participants aged 18 years and older in Jazan. The structured questionnaire assessed demographic information, awareness of cataracts and glaucoma, understanding of symptoms, and perceptions of treatment options. Data collection took place over four weeks, with statistical analysis performed using descriptive statistics to summarize findings. A total of 426 participants completed the survey. Of these, 43.9% (n = 186) were aware of cataracts, while only 28.1% (n = 119) recognized glaucoma. Awareness of cataract symptoms varied, with 43.4% (n = 184) identifying blurred vision; however, 71.5% (n = 303) reported being unaware of glaucoma. A significant majority (68.2%, n = 289) recognized surgical treatment for cataracts, but only 27.8% (n = 118) were aware of treatment options for glaucoma. High levels of uncertainty about both conditions suggest a critical lack of understanding in the community. This study emphasizes the need for improved awareness and understanding of cataracts and glaucoma in Jazan, Saudi Arabia. By implementing targeted public health strategies, healthcare providers can enhance knowledge, encourage regular eye examinations, and ultimately reduce the burden of visual impairment in the community.

A glaucoma micro-stent with diverging channel and stepped shaft structure based on microfluidic template processing technology

BackgroundMinimally invasive glaucoma surgery (MIGS) has experienced a surge in popularity in recent years. Glaucoma micro-stents serve as the foundation for these minimally invasive procedures. Nevertheless, the utilization of these stents still presents certain short-term and long-term complications. This study aims to elucidate the creation of a novel drainage stent implant featuring a diverging channel, produced through microfluidic template processing technology. Additionally, an analysis of the mechanical properties, biocompatibility, and feasibility of implantation is conducted.ResultsThe stress concentration value of the proposed stent is significantly lower, approximately two to three times smaller, compared to the currently available commercial XEN gel stent. This indicates a stronger resistance to bending in theory. Theoretical calculations further reveal that the initial drainage efficiency of the gradient diverging drainage stent is approximately 5.76 times higher than that of XEN stents. Notably, in vivo experiments conducted at the third month demonstrate a favorable biocompatibility profile without any observed cytotoxicity. Additionally, the drainage stent exhibits excellent material stability in an in vitro simulation environment.ConclusionsIn summary, the diverging drainage stent presents a novel approach to the cost-effective and efficient preparation process of minimally invasive glaucoma surgery (MIGS) devices, offering additional filtering treatment options for glaucoma.

QbD-driven thymoquinone laden nanoemulsion for glaucoma management: In vitro, ex vivo, and pre-clinical evaluation

The primary goal of the present research investigation is the development and evaluation of thymoquinone-loaded nanoemulsion (TMQ-NE) for glaucoma therapy. The Box-Behnken Design approach was used for optimization of the TMQ-NE formulation. The TMQ-NE was prepared with the low-energy method, and was evaluated for its physicochemical properties revealed 29.10 ± 0.87 nm droplet size with 0.096 ± 0.03 of polydispersity index. The TMQ-NE exhibited the 6.2 ± 0.2 pH and 302 ± 1.5mOsm/kg osmolarity. Release studies demonstrated that TMQ-NE released 84.87 ± 0.18% of thymoquinone, while ex vivo corneal permeability study showed around 90% of permeation. The safety and efficacy assessments were conducted using ex vivo HET-CAM assay and in vivo Draize test, where the formulation was found safe for ocular administration. The optimized TMQ-NE exhibited a significant reduction in intraocular pressure (IOP) by 39.59 ± 0.88% within 1.5 h post-administration in animal model. Conclusively, the findings promote thymoquinone as an optimistic treatment option for glaucoma, underscoring the potential of TMQ-NE as an effective ocular drug delivery system.

Oxymatrine impedes the progression of endotoxin-induced glaucoma via redox system modulations.

This study aimed to provide irrefutable evidence of the preventive effects of oxymatine (OMT) on a model of endotoxin induced glaucoma in Wistar rats which can be attributed to its anti-inflammatory, antioxidant, and TNF-α antagonistic properties. To assess the impact of OMT on uveitic glaucoma, the normal group received 100 μLdistilled water topically for 15 days, while the glaucoma control group was induced with uveitic glaucoma by applying 10 μLof 10 μg/mLlipopolysaccharide (LPS) topically for 3 consecutive days. The treatment groups were then given OMT solution at a volume of 50 μLwith varying doses of 0.25%, 0.5%, and 1% once a day via topical administration for 15 days. In addition, as a standard, the animals were also given 100 μLof 1% dorzolamide topically for 15 days. All ophthalmic dosing was carried out by pulling the lower eye-lid of the experimental animals and administration of the respective solutions. The study uses cutting-edge real-time imaging of the retinal vasculature in anesthetized animals, postsacrifice lenticular picturization and biochemical evidence to support the changes in the retinal layers. LPS induced animals demonstrated increased IOP, disrupted antioxidant systems, massive lipid damage, enhanced TNF-α activity and changes in intracellular ATPase and ionic activities. The damaged retinal vasculature and lenticular opacification further supported the biochemical evidence. However, using OMT at a 1% dosage effectively enhanced the antioxidant levels, regulated intracellular ion concentration and ATPases, decreased TNF-α activity, and counteracted mechanobiological changes in the visual front and retina. Moreover, OMT can successfully normalize intraocular pressure, making it a highly beneficial treatment option for glaucoma.

ChatGPT: is it good for our glaucoma patients?

PurposeOur study investigates ChatGPT and its ability to communicate with glaucoma patients.MethodsWe inputted eight glaucoma-related questions/topics found on the American Academy of Ophthalmology (AAO)’s website into ChatGPT. We used the Flesch–Kincaid test, Gunning Fog Index, SMOG Index, and Dale–Chall readability formula to evaluate the comprehensibility of its responses for patients. ChatGPT’s answers were compared with those found on the AAO’s website.ResultsChatGPT’s responses required reading comprehension of a higher grade level (average = grade 12.5 ± 1.6) than that of the text on the AAO’s website (average = 9.4 grade ± 3.5), (0.0384). For the eight responses, the key ophthalmic terms appeared 34 out of 86 times in the ChatGPT responses vs. 86 out of 86 times in the text on the AAO’s website. The term “eye doctor” appeared once in the ChatGPT text, but the formal term “ophthalmologist” did not appear. The term “ophthalmologist” appears 26 times on the AAO’s website. The word counts of the answers produced by ChatGPT and those on the AAO’s website were similar (p = 0.571), with phrases of a homogenous length.ConclusionChatGPT trains on the texts, phrases, and algorithms inputted by software engineers. As ophthalmologists, through our websites and journals, we should consider encoding the phrase “see an ophthalmologist”. Our medical assistants should sit with patients during their appointments to ensure that the text is accurate and that they fully comprehend its meaning. ChatGPT is effective for providing general information such as definitions or potential treatment options for glaucoma. However, ChatGPT has a tendency toward repetitive answers and, due to their elevated readability scores, these could be too difficult for a patient to read.

Provider use of a participatory decision-making style with African American patients with glaucoma

ObjectiveTo examine whether non-adherent African American patients with glaucoma who received a question prompt list and video intervention were more likely to be given treatment options, have their input included into treatment regimens, and rate their providers as using more of a participatory decision-making style. MethodsAfrican American patients with glaucoma taking one or more glaucoma medications and reported being non-adherent were randomized to a pre-visit video and glaucoma question prompt list intervention or usual care. Results189 African American patients with glaucoma participated. Providers gave patients treatment choices during 5.3% of visits and included patient input into treatment regimen decisions during 2.1% of visits. Male patients and patients with more years of education were significantly more likely to rate their providers as using more of a participatory decision-making style. ConclusionAfrican American patients with glaucoma rated their providers high on using a participatory decision-making style. Yet, providers infrequently presented non-adherent patients with medication treatment options, and it was rare for providers to include patient input into treatment decisions. Practice implicationsProviders should provide non-adherent patients with different glaucoma treatment options. Non-adherent African American patients with glaucoma should be encouraged to ask their providers for different medication treatment options.

Cyclophotocoagulation as a Minimally Invasive Treatment Option for Glaucoma.

Cyclophotocoagulation as a Minimally Invasive Treatment Option for Glaucoma.

Promising Role of Silk-Based Biomaterials for Ocular-Based Drug Delivery and Tissue Engineering.

Silk is a wonderful biopolymer that has a long history of medical applications. Surgical cords and medically authorised human analogues made of silk have a long history of use in management. We describe the use of silk in the treatment of eye diseases in this review by looking at the usage of silk fibroin for eye-related drug delivery applications and medication transfer to the eyes. During this ancient art endeavour, a reduced engineering project that employed silk as a platform for medicine delivery or a cell-filled matrix helped reignite interest. With considerable attention, this study explores the present usage of silk in ocular-based drug delivery. This paper also examines emerging developments with the use of silk as a biopolymer for the treatment of eye ailments. As treatment options for glaucoma, diabetic retinopathy, retinitis pigmentosa, and other retinal diseases and degenerations are developed, the trans-scleral route of drug delivery holds great promise for the selective, sustained-release delivery of these novel therapeutic compounds. We should expect a swarm of silk-inspired materials to enter clinical testing and use on the surface as the secrets of silk are unveiled. This article finishes with a discussion on potential silk power, which adds to better ideas and enhanced ocular medicine delivery.

A systematic approach to reduce intraocular pressure for the treatment of glaucoma.

Glaucoma is the leading cause of irreversible blindness due to increased intraocular pressure (IOP) in the eye. We have developed a novel treatment option for glaucoma based on a real-time IOP-dependent nitric oxide synthase (NOS) and packed in a therapeutic contact lens to reduce the IOP. First, 1.6 nmole nitric oxide was produced from the genetic chassis, which was optimized for isopropyl β-d-1-thiogalactopyranoside (IPTG) induction in a T7 expression system. For biosafety concerns to human being, the csgAD genes responsible for curli biofilm formation in Escherichia coli were co-expressed with NOS in the designated NOSAD strain to strengthen the adherence of cells to the contact lens, thereby preventing the contamination into the eyes. Moreover, NOSAD is a diaminopimelic acid (DAP) auxotrophic strain, which cannot survive without supplementation of DAP and reached the critical consideration of biosafety to the environment. We also demonstrated that the nitric oxide diffusion was 3.6-times enhanced from penetration into the aqueous humor of porcine eyes. The deformation ratio of the contact lens was correlated to the change of IOP by using a digital image correlation (DIC) system in a porcine eye model. The novel systematic approach provides an alternative treatment for glaucoma patients in the future.

Gene Expression Data for Investigating Glaucoma Treatment Options and Pharmacology in the Anterior Segment, State-of-the-Art and Future Directions.

Glaucoma treatment options as well as its etiology are far from understood. Gene expression (transcriptomics) data of the anterior segment of the eye can help by elucidating the molecular-mechanistic underpinnings, and we present an up-to-date description and discussion of what gene expression data are publicly available, and for which purposes these can be used. We feature the few resources covering all segments of the eye, and we then specifically focus on the anterior segment, and provide an extensive list of the Gene Expression Omnibus data that may be useful. We also feature single-cell data of relevance, particularly three datasets from tissues of relevance to aqueous humor outflow. We describe how the data have been used by researchers, by following up resource citations and data re-analyses. We discuss datasets and analyses pertaining to fibrosis following glaucoma surgery, and to glaucoma resulting from the use of steroids. We conclude by pointing out the current lack and underutilization of ocular gene expression data, and how the state of the art is expected to improve in the future.

Corneal Endothelial Cell Loss in Patients After Minimally Invasive Glaucoma Surgery: Current Perspectives.

Minimally invasive glaucoma surgery (MIGS) is a rapidly expanding category of surgical glaucoma treatment options that offer a superior safety profile compared with traditional approaches for reducing intraocular pressure. However, MIGS may cause corneal endothelial cell loss; therefore, it has been receiving increasing attention. This systematic review aimed to evaluate and compare the rate and degree of corneal endothelial loss after MIGS. First, this paper presents an overview of the theoretical effectiveness of MIGS, the fundamental aspects regarding the roles of endothelial cells, and the effect of cataract surgery on the quality and count of endothelial cells. Further, we detail the various surgical techniques involved in MIGS, the development of these techniques over the time, and clinical aspects to consider with respect to the endothelial cell count. We discuss in detail the COMPASS-XT study, which was based on data collected over 5 years, reported that withdrawal of the CyPass Micro-Stent (Alcon Laboratories) yielded increased corneal endothelial cell loss. Generally, MIGS procedures are considered safe, with the incidence of complications ranging from 1% to 20% depending on the surgery type; however, there is still need for studies with longer follow-up. Thus, an adequate count of endothelial cells in the central cornea portion is recommended as necessary for candidate patients for MIGS.

Efficacy and Patient Tolerability of Omidenepag Isopropyl in the Treatment of Glaucoma and Ocular Hypertension.

Current therapeutic approaches for glaucoma aim to reduce intraocular pressure (IOP), which is the only available and reliable strategy proven to control the risk of disease development and progression. Omidenepag isopropyl (OMDI) is a novel topical ocular hypotensive agent that was launched onto the market for the treatment of glaucoma and ocular hypertension (OHT). After topical instillation and during corneal penetration, OMDI is converted into the active metabolite omidenepag (OMD), which behaves as a non-prostaglandin, selective E-prostanoid subtype 2 (EP2) receptor agonist. The topical administration of 0.002% OMDI once-daily (QD) possesses a 20–35% IOP-lowering effect, comparable to that of prostaglandin analogs targeting F-prostanoid (FP) receptor QD, which are the current first-line for pharmaceutical reduction of IOP. However, the mechanism of action and adverse events (AEs) of OMDI are different from those of FP receptor agonists. OMDI reduces IOP by enhancing both conventional trabecular and uveoscleral outflow facilities without complications of prostaglandin-associated periorbitopathy (PAP) seen with FP receptor agonists. Moreover, OMDI was also effective and well-tolerated in non-/poor responders to latanoprost and showed a stable IOP-lowering effect for one year, and its concomitant use with timolol enhanced the IOP-lowering effect. OMDI demonstrated acceptable safety and tolerability with good adherence and can be used in almost every patient. However, OMDI has some AEs such as conjunctival hyperemia, corneal thickening, macular edema/cystoid macular edema and ocular inflammation. Moreover, OMDI is contraindicated in patients who are allergic to the product, in aphakic or pseudophakic eyes, and in combination with tafluprost eye drops. If used appropriately in the right patients, OMDI could be an effective treatment option for glaucoma and OHT as a first-line alternative to FP agonists. Here, we summarize the results of clinical studies of OMDI and discuss its efficacy and patient tolerability in glaucoma and OHT in this review.

Mini-Review on Bioanalytical Estimation of Brinzolamide

Abstract: Brinzolamide is a treatment option for glaucoma. As glaucoma is the third leading cause of blindness, there is a need for analytical methods to obtain an effective drug with great precision and accuracy. Even if brinzolamide is official in IP and USP, different analytical methods still need to be brought in one place, which would help attain better results and easy comparison for other analysis specifications and procedures. This review helps to understand and gather different analysis techniques or biological fluid techniques of brinzolamide in a dosage form. These techniques include UV spectroscopy, HPLC, LC-MS, and TLC densitometry.

Cross-sectional Survey to Determine the Awareness and Uptake of Glaucoma Surgery

Introduction: This study aimed to determine the awareness and uptake of surgery as a treatment option in patients with glaucoma on medical treatment.Methods: A cross-sectional survey was conducted among consenting patients with primary glaucoma who were on medical treatment. The survey was conducted in two eye care facilities (government-owned and private). After responding to a questionnaire, patients had ocular examinations, including visual acuity, anterior/posterior segment examinations, gonioscopy and central visual field testing. Information was obtained on the patients’ awareness of a surgical option, and reasons for non-uptake among those offered surgery were recorded. Logistic regression analysis was used to identify possible predictors of awareness of glaucoma.Results: Across both facilities, 299 patients with glaucoma with a mean age of 63.9 years participated in this study. There were 167 (55.9%) male and 132 (44.1%) female participants. Two hundred and sixty-seven (89.3%) had a formal education, and of the 169 evaluated for visual fields in the worse eye, 129 (76.3%) had severe (advanced) glaucoma. Only 79 (26.4%) of the participants were aware of surgery as a treatment option for glaucoma. The multivariate analysis found that female patients, patients from the private eye care facility and patients with primary angle closure glaucoma patients were more likely to be aware of glaucoma surgery than male patients, patients from the government-owned eye care facility and patients with primary open-angle glaucoma. Patients with primary angle closure glaucoma were more likely to be aware of glaucoma surgery than those with primary open-angle glaucoma. Cost was identified as the major barrier to the uptake of glaucoma surgery when it was recommended, followed by fear of blindness. Age, level of education and severity of disease had no statistical relationship to awareness of glaucoma surgery.Conclusion: Incorporating routine glaucoma education and counselling into glaucoma care protocols will likely improve awareness of glaucoma surgery as a treatment option.

A novel EyePhone© App for improving adherence to glaucoma therapy.

Despite advances in glaucoma treatment options, patient adherence and compliance remain very low. The EyePhone© App is a free non-commercial reminder application designed specifically for the needs of glaucoma patients. In this study, we evaluated its usefulness in improving adherence to medical treatment among glaucoma patients. This is a prospective multicenter interventional study. Glaucoma patients were recruited from a tertiary center and a large community glaucoma service center. After a short explanation, the EyePhone© App was installed on their smartphone device, and the notifications for the current medical treatment were entered. After enrollment and at 1-month follow-up, subjects completed the Morisky Medication Adherence Scale (MMAS-8) and the Quality of Life and Glaucoma 17-item (GlauQOL-17) questionnaires for evaluation of adherence and QOL, respectively. In the study, 133 patients (71 men and 62 women) aged 62±15.5 years and using 2.0±0.9 IOP-lowering drugs participated. The proportion of highly adherent subjects improved from 29.3% (39/133) at baseline to 42.1% (56/133) at follow-up (P < 0.001), and the proportion of poorly adherent subjects decreased from 29.3 (39/133) to 20.3% (27/133) at follow-up (P = 0.012). QOL also improved, as evidenced by a significant increase in the GlauQOL-17 score (P < 0.05). In a subgroup of patients for whom IOP measurements were available, IOP reduced by 0.92 mmHg (P = 0.069). Significant improvements in glaucoma adherence and QOL were achieved among poorly adherent glaucoma patients after 1 month of using the EyePhone© App.

Improved Treatment Options for Glaucoma with Brimonidine-Loaded Lipid DNA Nanoparticles.

Glaucoma is the second leading cause of irreversible blindness worldwide. Among others, elevated intraocular pressure (IOP) is one of the hallmarks of the disease. Antiglaucoma drugs such as brimonidine can lower the IOP but their adherence to the ocular surface is low, leading to a low drug uptake. This results in a frequent dropping regime causing low compliance by the patients. Lipid DNA nanoparticles (NPs) have the intrinsic ability to bind to the ocular surface and can be loaded with different drugs. Here, we report DNA NPs functionalized for loading of brimonidine through specific aptamers and via hydrophobic interactions with double stranded micelles. Both NP systems exhibited improved affinity toward the cornea and retained release of the drug as compared to controls both in vitro and in vivo. Both NP types were able to lower the IOP in living animals significantly more than pristine brimonidine. Importantly, the brimonidine-loaded NPs showed no toxicity and improved efficacy and hence should improve compliance. In conclusion, this drug-delivery system offers high chances of an improved treatment for glaucoma and thus preserving vision in the aging population.

WITHDRAWN: Electronic Medical Record Design and Glaucoma Surgery Rehabilitation Nursing Based on Embedded System

Abstract The health sector of developing countries, India, such as mobile computing and cloud computing, has begun to use the latest new technology. Glaucoma is a chronic neurodegenerative disease of the optic nerve. The purpose of therapy is to prevent optic nerve damage's onset and progression by lowering intraocular pressure. The current treatment options, local/systemic drugs, reduced the production of increasing or aqueous humor, including laser treatment targeting the trabecular meshwork and ciliary body and the incision surgery. The collection of enormous capacity, storage, processing, and digital multimedia retrieval is referred to as electronic medical records. Electronic medical records have been constructed with high patient safety attention images. Surgery, documentation of the management process, despite the poor compliance with mandatory tolerated dose therapy, and the case is the largest in glaucomatous optic neuropathy. Please provide an overview of the surgeon to the available treatment options for glaucoma. The possible surgical method, change over an improved time to improve the patient's prognosis and the visual recovery, is full of intraoperative, postoperative complications. Each possible surgical treatment plan's risks and benefits are strictly evaluated; will need to adjust to meet a particular patient's needs. Here is the current evidence is insufficient to establish any of the advantages of these surgeries on top of the other person. The possible surgical method, change over an improved time to improve the patient's prognosis and the visual recovery, is full of intraoperative, postoperative complications.

Intraocular pressure measurement techniques: Current concepts and a review

According to the World Health Organization, glaucoma is the leading cause of irreversible blindness worldwide. Although intraocular pressure (IOP) is not considered any more to be a defining feature of the disease, its lowering remains the only treatment option for glaucoma. Therefore accurate and precise measurement of IOP is the cornerstone of glaucoma.Intraocular pressure is a highly dynamic physiological parameter with individual circadian rhythms. The main limitation of current tonometry methods remains the static and mostly office-based nature of their measurements.

Minimally Invasive Glaucoma Surgery: Where Is the Evidence?

Purpose:The last decade has witnessed an unprecedented growth in glaucoma treatment options through the introduction of minimally invasive glaucoma surgeries (MIGS). The aim of the present review is to provide an understanding of the currently available MIGS and to examine what data are currently available to guide treatment choice.Design:Meta-analysis and systematic review of randomized and non-randomized control trials.Methods:Out of 2567 articles identified, a total of 77 articles were retained for analysis, including 28 comparative studies and 12 randomized control trials. Overall, 7570 eyes were included. When data permitted, the weighted mean difference in intraocular pressure reduction was calculated for comparison purposes.Results:Weighted mean intraocular pressure reductions from all analyzed studies were: 15.3% (iStent), 29.1% (iStent inject), 36.2% (ab interno canaloplasty), 34.4% (Hydrus), 36.5% (gonioscopically-assisted transluminal trabeculotomy), 24.0% (trabectome), 25.1% (Kahook dual blade), 30.2% (Cypass), 38.8% (XEN), and 50.0% (Preserflo).Conclusions:One of the advantages of the heterogenous range of available MIGS options is the chance to tailor therapy in an individualized manner. However, high-quality data are required to make this choice more than an educated guess. Overall, this review confirms the efficiency of assessed MIGS compared with standalone phacoemulsification, but it highlights that only few studies compare different MIGS techniques and even fewer assess MIGS against criterion standard treatments. Current evidence, while non-negligible, is mostly limited to heterogenous nonrandomized studies and uncontrolled retrospective comparisons, with few quality randomized control trials. We suggest that future research should be comparative and include relevant comparators, standardized to report key outcome features, long-term to assess sustainability and late complications, and ideally randomized.

Patient attitudes toward novel glaucoma drug delivery approaches.

Understanding patients' attitudes toward novel therapeutic options can help guide providers in personalizing treatment regimens for glaucoma patients. This study aimed to determine factors associated with acceptance of new drug delivery options among glaucoma patients. A total of 199 patient volunteers participated in an interviewer-administered survey from June to August 2016 at the Glaucoma Service of Massachusetts Eye and Ear. The questionnaire was designed to determine acceptance of 6 drug delivery approaches: (1) triple combination eye drop, (2) microdose eye spray, (3) drug-eluting contact lens, (4) drug-eluting periocular ring insert, (5) injectable subconjunctival drug insert, and (6) injectable anterior chamber implant. Other factors analyzed included self-reported demographics, disease severity, and prior ocular history. The average respondent age was 63.2 ± 15.1 years; 48% were female. For approaches 1-6 listed above, overall acceptance rates were, respectively, 85%, 54%, 31%, 43%, 32%, and 30%. Patients with greater disease severity and prior incisional glaucoma surgery were more likely to pursue alternatives to traditional eye drops. There is limited acceptance of alternatives to traditional eye drop medications among glaucoma patients. Understanding motivating factors and potential barriers to patient acceptance of novel drug delivery approaches is important in how providers will incorporate these glaucoma treatment options into practice.