Topical netarsudil for the treatment of primary corneal endothelial degeneration in dogs.

This study evaluated the tolerability and efficacy of the topical rho-kinase inhibitor netarsudil for canine primary corneal endothelial degeneration (PCED). Twenty-six eyes of 21 client-owned dogs with PCED were enrolled in a prospective, randomized, vehicle control clinical trial and received topical netarsudil 0.02% (Rhopressa®) or vehicle control twice daily (BID) for the first 4 months. Then, all patients received netarsudil for the next 4 or 8 months. Complete ophthalmic examination, ultrasonic pachymetry, Fourier-domain optical coherence tomography, and in vivo confocal microscopy were performed at baseline and 1, 2, 4, 6, 8 and 12 months. Effect of netarsudil on central corneal thickness (CCT), percentage of cornea with edema, and endothelial cell density (ECD) were evaluated by repeated measures ANOVA. Kaplan-Meier curves and log-rank test were used to compare corneal edema and clinical progression of eyes in netarsudil versus vehicle control groups. All dogs developed conjunctival hyperemia in at least one eye while receiving netarsudil. Unilateral transient reticulated intraepithelial bullae and stromal hemorrhage were observed respectively in 2 dogs in the netarsudil group. Two dogs showed persistently decreased tear production while receiving netarsudil, requiring topical immunomodulatory treatment. No significant differences in CCT, ECD, corneal edema or clinical progression were observed between netarsudil or vehicle treated eyes. When comparing efficacy of topical netarsudil BID and topical ripasudil 0.4% administered four times daily from our previous study, dogs receiving ripasudil had significantly less progression than those receiving netarsudil.

The Neuropeptide α-Melanocyte-Stimulating Hormone Prevents Persistent Corneal Edema following Injury.

Corneal endothelial cells (CEnCs) regulate corneal hydration and maintain tissue transparency through their barrier and pump function. However, these cells exhibit limited regenerative capacity following injury. Currently, corneal transplantation is the only established therapy for restoring endothelial function, and there are no pharmacologic interventions available for restoring endothelial function. This study investigated the efficacy of the neuropeptide α-melanocyte-stimulating hormone (α-MSH) in promoting endothelial regeneration during the critical window between ocular injury and the onset of endothelial decompensation using an established murine model of injury using transcorneal freezing. Local administration of α-MSH following injury prevented corneal edema and opacity, reduced leukocyte infiltration, and limited CEnC apoptosis while promoting their proliferation. These results suggest that α-MSH has a proregenerative and cytoprotective function on CEnCs and shows promise as a therapy for the prevention and management of corneal endothelial dysfunction.

Monkeypox-Associated Disciform Keratitis.

PURPOSE: The purpose of this study was to describe a case of monkeypox (MPX)-associated disciform keratitis. METHODS: This is a case report. RESULTS: A 36-year-old male patient presented to the infectious diseases clinic with a 1-week history of disseminated pustular skin lesions, a 4-day history of constitutional symptoms, and redness in the left eye. Testing of blood, 2 skin lesions, and a conjunctival swab confirmed the presence of MPX virus by polymerase chain reaction. On ophthalmologic examination on the 17th day of illness, there was a corneal epithelial ridge that stained with fluorescein with disciform corneal edema and underlying keratic precipitates. The patient was treated with oral tecovirimat 600 mg twice a day for 14 days and topical prednisolone acetate 1% 4 times daily, starting 2 days later. On completion of oral treatment, his corneal findings had resolved except for a small subepithelial scar at which time topical steroids were tapered. CONCLUSIONS: MPX may cause disciform keratitis and scarring that closely resembles other ocular viral infections. Clinical trials are urgently needed to define the optimal management of human MPX infections and reduce vision loss.

Ripasudil Eyedrops Ameliorated Bullous Keratopathy Complicated with Cytomegalovirus Corneal Endotheliitis: A Case Report.

PURPOSE: We describe a case of bullous keratopathy complicated with cytomegalovirus (CMV) corneal endotheliitis that was successfully treated with ripasudil eye drops. METHODS: A retrospective case report. RESULTS: A 65-year-old female patient diagnosed with CMV-associated anterior uveitis in the right eye was referred to us when anterior uveitis recurred with bullous keratopathy. Initial best-corrected visual acuity (BCVA) was 0.4 (decimal visual acuity). Her condition did not improve with anti-CMV treatment, and BCVA decreased to 0.07. At this point, intraocular pressure (IOP) was 20 mmHg, and ripasudil eye drops were started for IOP control. After 1 month, not only had IOP decreased to 14 mm Hg but the condition of the corneal edema had also improved. The central corneal thickness decreased to a normal level, and the BCVA recovered to 0.8. CONCLUSION: Ripasudil eye drops not only lower IOP in patients with CMV corneal endotheliitis but may also have the potential to treat bullous keratopathy.

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.

Unilateral vortex keratopathy of unknown etiology.

A 54-year-old man with noncontributory medical history presented to an ophthalmologist in January 2022 after 10 days of irritation in his right eye. The patient recounts having felt something get into his eye and under his contact lens (CL) while he was climbing into his car, but he was unsure what the foreign body may have been. Initial examination by the clinician found uncorrected distance visual acuity of 20/100-2 with a corneal abrasion, 4+ corneal edema, and 3+ conjunctival injection, for which he was placed on topical antibiotics (ocuflox and tobradex) with a bandage CL. 1 week later, visual acuity was 20/80, corneal edema had improved, and he was noted to have corneal scarring and an epithelial defect. Tobradex was continued while prednisolone drops and preservative-free artificial tears were started. 1 week later, the patient had worsening visual acuity to 20/250 and was referred to our tertiary center. On initial consultation, the patient had an uncorrected distance visual acuity of 20/500 and an uncorrected near visual acuity of >J10 in the right eye. Slitlamp examination of the right eye was significant for vortex keratopathy and mild corneal pannus with 360-degree subtle conjunctivalization of the limbus ( Figure 1JOURNAL/jcrs/04.03/02158034-202210000-00022/figure1/v/2022-10-03T121249Z/r/image-tiff ). The corneal topograph was obtained showing significant surface irregularity on the Placido image ( Figure 2JOURNAL/jcrs/04.03/02158034-202210000-00022/figure2/v/2022-10-03T121249Z/r/image-tiff ). Examination of the left eye was unremarkable. The ocular history is significant for myopia of -4.0 diopters and CL use for 20 years. The patient admits to regularly wearing soft CLs for several days straight and only removing them for a few hours. Antibiotics were discontinued, corticosteroid drops were reduced in frequency, and the patient was continued on preservative-free artificial tears. What imaging might you consider? What is your differential diagnosis at this point? What would be the most appropriate surgical and/or medical interventions? What would you counsel in prognosis for this patient?

Reversible Corneal Decompensation Caused by a Topical Dorzolamide/Timolol Fixed Combination After Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: The purpose of this study was to report a case of acute corneal endothelial decompensation caused by a topical dorzolamide/timolol fixed combination (DTFC) after Descemet stripping automated endothelial keratoplasty. METHODS: A 75-year-old woman who was referred to our hospital with a chief complaint of visual disturbance in the right eye after cataract surgery. Anterior segment optical coherence tomography identified an extensive defect in Descemet membrane. The patient subsequently underwent uneventful Descemet stripping automated endothelial keratoplasty surgery for persistent corneal edema. Two weeks after surgery, she had been prescribed topical DTFC twice daily to control elevated intraocular pressure. On the day she started using the eye drops, the patient noticed an acute deterioration of visual acuity. Severe corneal edema was detected at follow-up 5 days later. RESULTS: The topical DTFC was stopped immediately. Thereafter, the corneal edema improved gradually, and there was a reduction in corneal thickness. CONCLUSIONS: Topical DTFC should be used with caution after corneal endothelial transplantation because of the possibility of iatrogenic corneal endothelial dysfunction.

Amantadine therapy for Parkinson's Disease: In Vivo Confocal Microscopy corneal findings, case report and revision of literature.

BACKGROUND: To report a case of a patient showing bilateral corneal opacities after amantadine chronic treatment for Parkinson's Disease (PD) and corneal edema associated with intra-epithelial and -endothelial depositions. After amantadine discontinuation a complete clinical remission with only a partial ultrastructural corneal recovery was reported. CASE PRESENTATION: We describe a 78-year-old man with non-medical-responding bilateral corneal edema in treatment with systemic Amantadine for PD. In vivo confocal Microscopy (IVCM) analysis revealed hyperreflective particles at the epithelial level and expanded hyperreflective keratocyte and a disarrangement of stromal lamellae; endothelial cells showed hyperreflective intracellular inclusions in central and in peripheral areas with central polymegatism and pleomorphism. After 1 and 6 months the amantadine discontinuation, the absence of bilateral corneal edema and opacities were noted at the slit lamp examination, associated with the disappearance of epithelial and stromal abnormalities, but the persistence of endothelial hyperreflective deposits with a pleomorphism and polymegatism worsening at the IVCM exam. CONCLUSION: The evaluation of a patient's cornea 6 months after the discontinuation of systemic amantadine therapy showed a clinical complete remission, with a complete resolution of the bilateral corneal oedema. On the other hand, ultrastructurally, amantadine toxicity is a completely reversible phenomenon at the epithelial level; conversely IVCM showed persistent endothelial degradation.

Amantadine-induced bilateral corneal edema in a pediatric patient.

Amantadine was originally developed as an antiviral agent for influenza A. However, it also has off-label uses for Parkinson disease, multiple sclerosis, and in the management of extrapyramidal symptoms. The mechanism of action in these conditions has yet to be elucidated. Ocular side effects from systemic amantadine are rare but have been described in three previous reports of amantadine-associated corneal edema in the pediatric population. We present an additional case of amantadine-associated transient visual impairment in a patient, which was associated with significant regression and worsening of his underlying neurodevelopmental status.

Canine endotheliitis: Clinical characteristics, advanced imaging features, and treatment.

OBJECTIVE: To describe the clinical findings, multimodal corneal imaging features and treatment in canine patients diagnosed with endotheliitis. ANIMALS STUDIED: Four canine patients met inclusion criteria for bilateral corneal disease with endothelial inflammation and secondary corneal edema that responded to topical anti-inflammatory treatment. METHODS: The patients selected underwent a complete ophthalmic examination with emphasis on the cornea including ultrasound pachymetry (USP), Fourier-domain optical coherence tomography (FD-OCT), in vivo confocal microscopy (IVCM), and digital slit lamp photography. RESULTS: All patients in this study demonstrated thickened corneas due to edema with USP and FD-OCT. With IVCM, mild to severe polymegathism and pleomorphism of corneal endothelial cells, reduced endothelial cell density, hyperreflective keratic precipitates (KPs), and extracellular debris as well as hyporeflective pseudoguttata were observed. With FD-OCT, hyperreflective KPs were commonly observed on the inferior cornea. Clinical examination and advanced imaging results were consistent with a diagnosis of endotheliitis. All patients initially responded to topical anti-inflammatory treatment and required continued therapy; two patients also received topical netarsudil, a rho-associated coiled-coil kinase inhibitor. CONCLUSION: Endotheliitis should be considered for canine patients with bilateral edema that is most severe in the inferior cornea. Careful inspection of Descemet's membrane-endothelial complex should be performed for KPs or inflammatory debris. Chronic administration of topical anti-inflammatories may be necessary to prevent flare-ups of endotheliitis.

Multi modal imaging in corneal edema after corneal collagen cross-linking (CXL); a case-based literature review.

BACKGROUND: Keratoconus (KCN) is a common ectatic disorder of the cornea. Corneal collagen cross-linking (CXL) is used as an effective option to slowdown the disease progression. Although CXL is considered a safe procedure, corneal endothelial damage, especially in corneal thickness of less than 400 µm, has been reported. CASE PRESENTATION: A 25-year-old man known case of KCN was referred with complaints about blurred vision and discomfort of the right eye 3 days after performing CXL. The preoperative thinnest point was 461 µm. His presenting BCVA was CF at 1 m. Examination showed central corneal edema and stromal haziness. ASOCT demonstrated increased central corneal thickness and very deep CXL line. In the confocal scan, anterior stroma showed hyper-reflective lines without recognizable cells and nerves, the middle stroma showed rare active and edematous keratocytes and a hyper-reflective reticular pattern with elongated keratocytes and needle-like structures involving the posterior stroma indicated increased depth of CXL. To manage the patient, debridement of loosened epithelium was done. Non-preservative steroid 1% eye drop was prescribed frequently. The corneal edema was completely resolved during 2 months with no need for surgical procedure and BCVA of 20/30 in his right eye. CONCLUSION: The corneal thickness of more than 400 µm cannot guarantee the absence of corneal edema after corneal collagen cross-linking, which can pertain to several factors such as inadvertently using of higher energy as well as the incorrect observance of all guidelines, instructions, and other precautions, even by a trained surgeon.

Rhopressa-induced corneal edema: a case report.

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. CASE PRESENTATION: 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.

Topical administration of the kappa opioid receptor agonist nalfurafine suppresses corneal neovascularization and inflammation.

Corneal neovascularization (CNV) causes higher-order aberrations, corneal edema, ocular inflammation, and corneal transplant rejection, thereby decreasing visual acuity. In this study, we investigated the effects of topical administration of the kappa opioid receptor agonist nalfurafine (TRK-820) on CNV. To induce CNV, intrastromal corneal sutures were placed on the corneal stroma of BALB/c mice for 2 weeks. Nalfurafine (0.1 µg/2 µL/eye) was topically administered to the cornea once or twice daily after CNV induction. The CNV score, immune cell infiltration, and mRNA levels of angiogenic and pro-inflammatory factors in neovascularized corneas were evaluated using slit-lamp microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction. The mRNA expression of the kappa opioid receptor gene Oprk1 was significantly upregulated following CNV induction. Topical administration of nalfurafine twice daily significantly suppressed CNV and lymphangiogenesis, as well as reduced the mRNA levels of angiogenic and pro-inflammatory factors in the neovascularized corneas. Moreover, nalfurafine administration twice daily reduced the numbers of infiltrating leukocytes, neutrophils, macrophages, and interferon-γ-producing CD4+ T cells in the neovascularized corneas. In this study, we demonstrated that topical administration of nalfurafine suppressed local CNV in a mouse model along with the activation of KOR, suggesting that nalfurafine may prevent and control CNV in humans.

Hyperosmolar Eye Drops for Diurnal Corneal Edema in Fuchs' Endothelial Dystrophy: A Double-Masked, Randomized Controlled Trial.

PURPOSE: The Eye Drops for Early Morning-Associated Swelling (EDEMAS) trial assessed the efficacy of hyperosmolar eye drops on corneal edema resolution. DESIGN: Double-masked, randomized controlled trial of hyperosmolar eye drops. PARTICIPANTS: Participants with Fuchs' dystrophy scheduled for Descemet membrane endothelial keratoplasty. METHODS: One eye was randomized to hyperosmolar eye drops (treatment); the fellow eye was randomized to artificial tears (placebo). After baseline examination in the afternoon, corneas were examined using Scheimpflug tomography after eye opening in the morning. Participants received eye drops twice. Imaging was repeated every 30 minutes up to 4 hours. MAIN OUTCOME MEASURES: Decrease in central corneal thickness 1 hour after eye opening (primary end point), corneal thickness, subjective visual function, glare, visual acuity, and adverse events (AEs) (secondary end points). RESULTS: A total of 68 participants received the allocated intervention (59 eyes received treatment; 55 eyes received placebo). All eyes had stromal edema; none had epithelial edema. Corneal thickness was 626 µm in the treatment arm and 622 µm in the placebo arm after eye opening, indicating an early morning edema compared with baseline of +21 µm and +24 µm, respectively. Decrease in corneal thickness after 1 hour was -10.5 µm in the treatment arm (95% confidence interval [CI], -12.8 to -8.2) and -11.2 µm (95% CI, -13.6 to -8.9) in the placebo arm (between-arm difference, 0.7 µm, 95% CI, -2.0 to 3.5; P = 0.59), indicating no clinically relevant effect of hyperosmolar eye drops on early morning corneal edema. Results were not compatible with a relevant treatment effect on corneal thickness, visual acuity, and glare over the entire course of the study. Increase in subjective visual function was less rapid in the treatment arm than in the placebo arm. Adverse events, most commonly burning after eye drop application, were more common with treatment (30 eyes) than placebo (1 eye; risk difference, 49 percentage points; 95% CI, 36-62). CONCLUSIONS: In this double-masked, randomized controlled trial, resolution of early morning stromal edema was not accelerated by hyperosmolar eye drops, which more frequently caused AEs. These results are not compatible with a clinically relevant effect of hyperosmolar eye drops and do not support their routine use.

Randomized, Double-Masked, Pilot Study of Netarsudil 0.02% Ophthalmic Solution for Treatment of Corneal Edema in Fuchs Dystrophy.

PURPOSE: To evaluate off-label use of netarsudil 0.02% for treatment of corneal edema associated with Fuchs dystrophy. DESIGN: Prospective, randomized clinical trial. METHODS: Twenty-nine subjects with symptomatic Fuchs dystrophy were enrolled and randomized to use netarsudil or placebo eye drops once daily for 3 months. The primary outcomes were the change in central corneal thickness between baseline and 1 month and between baseline and 3 months. Secondary outcomes included change in scotopic corrected distance visual acuity (CDVA) at 3 months and change in scores on a visual disability questionnaire validated for use with Fuchs dystrophy. RESULTS: Compared with use of placebo, use of netarsudil produced significant reduction in central corneal thickness at 1 month (mean difference, -20 µm; 95% confidence interval, -32 to -9 µm) and 3 months (mean difference, -26 µm; 95% confidence interval, -39 to -12 µm) and significant improvement in scotopic CDVA at 3 months (mean difference +1.6 lines; 95% confidence interval, 0.2-3.0 lines). Scores on the visual disability questionnaire did not change significantly in either arm or differ significantly between arms. One subject assigned to netarsudil had baseline epithelial bullae and withdrew from the study because of disabling glare. CONCLUSIONS: Use of netarsudil was associated with reduction of corneal edema and improvement in scotopic CDVA in Fuchs dystrophy patients. Further study is needed to more fully assess patient satisfaction and visual acuity under various lighting conditions and to compare use of netarsudil with other treatment options such as endothelial keratoplasty.

Evaluating the safety and efficacy of compression sutures with intracameral perfluoropropane (C3F8) in the management of acute corneal hydrops.

BACKGROUND: To evaluate the safety and efficacy of using corneal compression sutures with intracameral perfluoropropane (C3F8) in patients presenting with acute corneal hydrops in ectatic disorders. METHODS: A retrospective analysis was done for 43 eyes of patients of acute corneal hydrops, managed using a combination of intracameral 14% C3F8 and full-thickness compression sutures. Time for resolution of edema, corneal thickness (CT) change on anterior segment ocular coherence tomography (ASOCT), and visual outcomes were assessed. RESULTS: Corneal edema resolved with a mean duration of 14.8 ± 3.5 days (range 10-21). The mean CT on ASOCT decreased from a mean of 1437 µm (689-2770 µm) preoperatively to 543 µm (434 -66 µm) on the complete resolution of corneal edema. CONCLUSION: Our results suggest that full-thickness compression sutures and intracameral C3F8 injection can restore the imperviousness of posterior stroma. This technique appears to be a safe and effective technique for faster resolution of corneal edema post hydrops.