Proper hydration and the clarity of the cornea are maintained through the crucial function of the corneal endothelium. Inflammation of the corneal endothelium, known as endotheliitis, can disrupt endothelial function, resulting in alterations to vision. Corneal endotheliitis is characterised by corneal oedema, the presence of keratic precipitates, inflammation within the anterior chamber, and occasionally, limbal injection, neovascularisation, and the concurrent or overlapping presence of uveitis. The aetiology of this condition is diverse, predominantly viral, but it may also be drug-induced, result from bacterial or fungal infections, be associated with systemic diseases and procedures, or remain idiopathic with no identifiable cause. To date, no standardised protocol for the treatment of this ocular disease exists, and in severe cases, corneal transplantation may be required. A 31-year-old male was transferred to our hospital for the management of corneal endothelial decompensation resulting from corneal endotheliitis. Hormonal therapy and antiviral medications proved ineffective, rendering the patient a candidate for corneal transplantation. As a final measure, treatment with the ROCK inhibitor netarsudil was initiated. The patient demonstrated significant improvement in symptoms, and the inflammation was successfully managed after nine months. In this study, a novel approach employing ROCK inhibitor therapy was utilised for the treatment of corneal endotheliitis, leading to marked recovery during patient follow-up. This case report represents the inaugural application of the ROCK inhibitor netarsudil in managing corneal endothelial decompensation attributed to corneal endotheliitis. These findings suggest that this method warrants consideration as a potential novel treatment option for similar conditions.

Rho-associated kinase inhibitors have been used in glaucoma management for reducing intraocular pressure. Their role in treating corneal endothelial damage and promoting corneal epithelial healing has also been reported. Presented is a case report demonstrating healing of a previously nonresponsive neurotrophic ulcer with addition of the Rho-associated kinase inhibitor, netarsudil.
Early in vitro -based research on corneal application of Rho-associated kinase inhibitors has shown these molecules to be beneficial to corneal epithelial wound healing. The presented case supports their use in epithelial disease. It is the author\'s hope that this will inspire further investigation.
Presented here is a case report describing the use of netarsudil, a Rho-associated kinase inhibitor in the management of a neurotrophic corneal ulcer that was nonresponsive to frontline therapy. The application of netarsudil was followed by rapid healing of the defect, although a concomitant increase in mucous production was also noted.
This case supports the use of netarsudil as an agonist of epithelial healing, although further research is needed.

Extremophiles produce macromolecules which inhibit ice recrystallization, but there is increasing interest in discovering and developing small molecules that can modulate ice growth. Realizing their potential requires an understanding of how these molecules function at the atomistic level. Here, we report the discovery that the amino acid l-α-alanine demonstrates ice recrystallization inhibition (IRI) activity, functioning at 100 mM (∼10 mg/mL). We combined experimental assays with molecular simulations to investigate this IRI agent, drawing comparison to β-alanine, an isomer of l-α-alanine which displays no IRI activity. We found that the difference in the IRI activity of these molecules does not originate from their ice binding affinity, but from their capacity to (not) become overgrown, dictated by the degree of structural (in)compatibility within the growing ice lattice. These findings shed new light on the microscopic mechanisms of small molecule cryoprotectants, particularly in terms of their molecular structure and overgrowth by ice.

UNASSIGNED: The Rho kinase inhibitor netarsudil is a recently approved therapeutic option for the management of increased intraocular pressure in the United States. Although phase 3 clinical trials noted corneal changes related to the medication-namely, nonvisually-significant corneal verticillata-descriptions of a unique form of cystic epithelial edema began to surface as netarsudil (and its sister drug ripasudil, approved in Japan) gained widespread use. This series adds 3 new cases and reviews the current literature on this unique side effect.

Intracorneal hemorrhages are a rare finding generally associated with surgery or trauma. There is no consensus on preferred management except eliminating or addressing the causative mechanism in hopes of reducing the risk of corneal haze or scarring.
This case highlights a rare adverse outcome of intracorneal hemorrhages occurring after recent initiation of netarsudil, possibly exacerbated by scleral contact lens wear in a patient with open-angle glaucoma and limbal stem cell deficiency.
A 77-year-old man using scleral contact lenses for therapeutic management of limbal stem cell deficiency started netarsudil for open-angle glaucoma. During an annual follow-up to adjust his scleral contact lenses, the patient developed peripheral intracorneal hemorrhages bilaterally. The intracorneal hemorrhages resolved over the course of 10 weeks after minor adjustments were made to the scleral contact lens fit and netasurdil was discontinued. Visual acuity and intraocular pressure remained stable throughout.
There are few reports of intracorneal hemorrhages associated with scleral contact lens use and even fewer associated with the use of netarsudil. This case proposes several possible causes of the intracorneal hemorrhages, including topical rho-associated kinase inhibitors, contact lens wear, and trauma. Further studies are needed to determine if netarsudil is associated with intracorneal hemorrhages, to understand the sequelae of intracorneal hemorrhages in netarsudil therapy, and to recommend management when intracorneal hemorrhages manifest with netarsudil use.

BACKGROUND: Rhopressa (netarsudil) has recently been added to the arsenal of treatment for open-angle glaucoma. It is an effective norepinephrine transporter and Rho-associated protein kinase (ROCK) inhibitor used to decrease intraocular pressure (IOP), with the most common side effect being conjunctival hyperemia.
METHODS: We report a unique case of Rhopressa-induced corneal edema in a 79-year-old African-American woman, which resolved after discontinuation. She had a history of smoking one cigarette per day and did not consume alcohol. She had no history of corneal edema or uveitis.
CONCLUSIONS: Previous case reports have documented patients with Rhopressa-induced corneal edema; however, they have all had a preexisting history of corneal edema or uveitis. We believe that this is a unique case of Rhopressa-induced corneal edema in a relatively healthy eye. While Rhopressa is effective in managing glaucoma, there may be effects of treatment that are still unknown. We will discuss clinical findings of our case, along with a review of previous literature on Rhopressa and novel ROCK inhibitors. We hope that we can add to the existing body of literature and invite further investigation of Rhopressa and ROCK inhibitors and their effects on the cornea.

OBJECTIVE: To describe 3 cases of corneal clearance after the use of topical rho-kinase inhibitor, netarsudil, in the setting of endothelial cell dysfunction in comparison to one case without corneal clearance after the use of netarsudil.
METHODS: Four patients presenting to a busy academic clinical corneal practice with visual complaints from corneal edema secondary to endothelial cell dysfunction were treated with topical netarsudil one drop daily in the affected eye.
RESULTS: Corneal clearance was observed in 1) a case of peripheral corneal edema in the setting of iridocorneal endothelial syndrome after 4 weeks on netarsudil, 2) a case of corneal edema in the setting of early penetrating keratoplasty graft failure after 2-week use of netarsudil, and 3) a case of corneal edema in the setting of chronic penetrating keratoplasty graft failure after 4-week use of netarsudil. Corneal clearance was not observed in a case of corneal edema in the setting of pseudophakic bullous keratopathy from previous complicated intraocular lens exchange surgery with placement of an anterior chamber intraocular lens after the use of netarsudil for 12 weeks.
CONCLUSIONS: Addition of topical rho-kinase inhibitor in the form of netarsudil can result in corneal clearance in a variety of certain cases of endothelial cell dysfunction, not previously documented in the literature.

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Hyperammonemia is an important adverse event associated with 5-fluorouracil (5FU) from 5FU metabolite accumulation. We present a case of an advanced gastric cancer patient with chronic renal failure, who was treated with 5FU/leucovorin (LV) infusion chemotherapy (2-h infusion of LV and 5FU bolus followed by 46-h 5FU continuous infusion on day 1; repeated every 2 weeks) and developed hyperammonemia, with the aim of exploring an appropriate hemodialysis (HD) schedule to resolve its symptoms.
The blood concentrations of 5FU and its metabolites, α-fluoro-β-alanine (FBAL), and monofluoroacetate (FA) of a patient who had hyperammonemia from seven courses of palliative 5FU/LV therapy for gastric cancer were measured by liquid chromatography-mass spectrometry.
On the third day of the first cycle, the patient presented with symptomatic hyperammonemia relieved by emergency HD. Thereafter, the 5FU dose was reduced; however, in cycles 2-4, the patient developed symptomatic hyperammonemia and underwent HD on day 3 for hyperammonemia management. In cycles 5-7, the timing of scheduled HD administration was changed from day 3 to day 2, preventing symptomatic hyperammonemia. The maximum ammonia and 5FU metabolite levels were significantly lower in cycles 5-7 than in cycles 2-4 (NH3 75 ± 38 vs 303 ± 119 μg/dL, FBAL 13.7 ± 2.5 vs 19.7 ± 2.0 μg/mL, FA 204.0 ± 91.6 vs 395.9 ± 12.6 ng/mL, mean ± standard deviation, all p < 0.05). After seven cycles, partial response was confirmed.
HD on day 2 instead of 3 may prevent hyperammonemia in 5FU/LV therapy.

This is a descriptive case series of 3 patients with uncontrolled intraocular pressure that developed reticular corneal changes after initiating netarsudil (0.02%). In all cases, upon observing reticular corneal edema, netarsudil (0.02%) was stopped followed by disappearance of corneal honeycombing. With the increasing use of this novel glaucoma medication, potentially more rare side effects will be observed. Reticular corneal edema or corneal honeycombing is an ocular examination finding that can rarely occur after initiating netarsudil (0.02%) regardless of prior corneal edema status. In our experience, the reticular changes resolve upon cessation of netarsudil.