Advanced Corneal Imaging in Keratoconus: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the diagnostic capabilities of the newest generation of corneal imaging devices for the identification of keratoconus. METHODS: Corneal imaging devices studied included tomographic platforms (Scheimpflug photography, OCT) and functional biomechanical devices (imaging an air impulse on the cornea). A literature search in the PubMed database for English language studies was last conducted in February 2023. The search yielded 469 citations, which were reviewed in abstract form. Of these, 147 were relevant to the assessment objectives and underwent full-text review. Forty-five articles met the criteria for inclusion and were assigned a level of evidence rating by the panel methodologist. Twenty-six articles were rated level II, and 19 articles were rated level III. There were no level I evidence studies of corneal imaging for the diagnosis of keratoconus found in the literature. To provide a common cross-study outcome measure, diagnostic sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were extracted. (A perfect diagnostic test that identifies all cases properly has an AUC of 1.0.) RESULTS: For the detection of keratoconus, sensitivities for all devices and parameters (e.g., anterior or posterior corneal curvature, corneal thickness) ranged from 65% to 100%. The majority of studies and parameters had sensitivities greater than 90%. The AUCs ranged from 0.82 to 1.00, with the majority greater than 0.90. Combined indices that integrated multiple parameters had an AUC in the mid-0.90 range. Keratoconus suspect detection performance was lower with AUCs ranging from 0.66 to 0.99, but most devices and parameters had sensitivities less than 90%. CONCLUSIONS: Modern corneal imaging devices provide improved characterization of the cornea and are accurate in detecting keratoconus with high AUCs ranging from 0.82 to 1.00. The detection of keratoconus suspects is less accurate with AUCs ranging from 0.66 to 0.99. Parameters based on single anatomic locations had a wide range of AUCs. Studies with combined indices using more data and parameters consistently reported high AUCs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Efficacy of Amniotic Membrane Grafting for the Treatment of Chemical and Thermal Ocular Surface Injuries: A Report by the American Academy of Ophthalmology.

OBJECTIVE: To evaluate the published literature on the efficacy of amniotic membrane grafting (AMG) in the management of acute chemical and thermal ocular surface burns with respect to the rate of corneal re-epithelialization and improvement of visual acuity or corneal clarity. METHODS: Literature searches were conducted in the PubMed database in May 2023 and updated in January 2024 and were limited to the English language without date restrictions. The searches yielded 474 citations; 58 were reviewed in full text, and 9 met the inclusion criteria. Four studies were rated level II, and 5 studies were rated level III. This assessment focuses on 3 level II articles that provided consistent primary and secondary outcomes but demonstrated suboptimal study design with respect to power calculations and lacked a priori sample-size calculations. RESULTS: Amniotic membrane grafting significantly improved corneal re-epithelialization compared with medical therapy alone in eyes with moderate-grade burns. For severely burned eyes, AMG demonstrated no advantage over medical therapy. Additionally, AMG demonstrated no significant advantage over medical therapy for improved visual acuity or corneal clarity for moderate or severe ocular surface burns. CONCLUSIONS: The best available level II evidence suggests that AMG in the setting of acute ocular surface burns has efficacy in hastening re-epithelialization in moderate burns. As an adjuvant to medical therapy, it did not demonstrate a benefit in improving re-epithelialization in severe burns or visual acuity or corneal clarity in either moderate or severe burns. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Outcomes and Complications of Limbal Stem Cell Allograft Transplantation: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the safety and outcomes of keratolimbal allograft (KLAL) transplantation and living-related conjunctival limbal allograft (lr-CLAL) transplantation for bilateral severe/total limbal stem cell deficiency (LSCD). METHODS: Literature searches were last conducted in the PubMed database in February 2023 and were limited to the English language. They yielded 523 citations; 76 were reviewed in full text, and 21 met the inclusion criteria. Two studies were rated level II, and the remaining 19 studies were rated level III. There were no level I studies. RESULTS: After KLAL surgery, best-corrected visual acuity (BCVA) improved in 42% to 92% of eyes at final follow-up (range, 12-95 months). The BCVA was unchanged in 17% to 39% of eyes and decreased in 8% to 29% of eyes. Two of 14 studies that evaluated the results of KLAL reported a notable decline in visual acuity over time postoperatively. Survival of KLAL was variable, ranging from 21% to 90% at last follow-up (range, 12-95 months) and decreased over time. For patients undergoing lr-CLAL surgery, BCVA improved in 31% to 100% of eyes at final follow-up (range, 16-49 months). Of the 9 studies evaluating lr-CLAL, 4 reported BCVA unchanged in 30% to 39% of patients, and 3 reported a decline in BCVA in 8% to 10% of patients. The survival rate of lr-CLAL ranged from 50% to 100% at final follow-up (range, 16-49 months). The most common complications were postoperative elevation of intraocular pressure, persistent epithelial defects, and acute allograft immune rejections. CONCLUSIONS: Given limited options for patients with bilateral LSCD, both KLAL and lr-CLAL are viable choices that may provide improvement of vision and ocular surface findings. The studies trend toward a lower rejection rate and graft failure with lr-CLAL. However, the level and duration of immunosuppression vary widely between the studies and may impact allograft rejections and long-term graft survival. Complications related to immunosuppression are minimal. Repeat surgery may be needed to maintain a viable ocular surface. Reasonable long-term success can be achieved with both KLAL and lr-CLAL with appropriate systemic immunosuppression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Safety and Efficacy of Epithelium-Off Corneal Collagen Cross-Linking for the Treatment of Corneal Ectasia: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the evidence on the safety and effectiveness of epithelium-off corneal collagen cross-linking (CXL) for the treatment of progressive corneal ectasia. METHODS: A literature search of the PubMed database was most recently conducted in March 2024 with no date restrictions and limited to studies published in English. The search identified 359 citations that were reviewed in abstract form, and 43 of these were reviewed in full text. High-quality randomized clinical trials comparing epithelium-off CXL with conservative treatment in patients who have keratoconus (KCN) and post-refractive surgery ectasia were included. The panel deemed 6 articles to be of sufficient relevance for inclusion, and these were assessed for quality by the panel methodologist; 5 were rated level I, and 1 was rated level II. There were no level III studies. RESULTS: This analysis includes 6 prospective, randomized controlled trials that evaluated the use of epithelium-off CXL to treat progressive KCN (5 studies) and post-laser refractive surgery ectasia (1 study), with a mean postoperative follow-up of 2.4 years (range, 1-5 years). All studies showed a decreased progression rate in treated patients compared with controls. Improvement in the maximum keratometry (Kmax) value, corrected distance visual acuity (CDVA), and uncorrected distance visual acuity (UDVA) was observed in the treatment groups compared with control groups. A decrease in corneal thickness was observed in both groups but was greater in the CXL group. Complications were rare. CONCLUSIONS: Epithelium-off CXL is effective in reducing the progression of KCN and post-laser refractive surgery ectasia in most treated patients with an acceptable safety profile. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

The role of eye banking with cell-based therapies.

PURPOSE OF REVIEW: Cell-based therapies are an exciting new frontier in managing corneal diseases. The introduction of these novel therapies may provide new alternatives to corneal transplantation and decrease the dependence on donor corneal tissue. These changes have the potential to significantly impact eye banking in the future. RECENT FINDINGS: The current article reviews current research involving cell-based therapy for treating corneal disorders, including cultivated limbal stem cell transplantation, limbal mesenchymal stem cells for stromal regeneration, and the use of human-cultivated endothelial cells. We will look at barriers to the development and implementation of these therapies. SUMMARY: As corneal surgery expands to include cell-based therapies; eye banks will need to redefine their role to support the everchanging landscape of corneal surgery and the decreased demand for corneal donor tissue.

Advances in eye banking and corneal tissue processing.

PURPOSE OF REVIEW: Eye bank processing of donor corneal tissue has helped to revolutionize and popularize newer corneal transplantation surgeries. In particular, Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) have benefited from eye banks preparing donor corneal tissue in advance of the surgery. As a result of these eye banking advances, surgeons have been able to rapidly adopt these new techniques. RECENT FINDINGS: This article reviews the techniques that are now being utilized to prepare donor tissue for endothelial keratoplasty (EK) with a focus on Ultrathin-DSAEK, prestamped, prestained, preloaded DMEK tissue, and advancements to improve the safety of donor corneal tissue. SUMMARY: Collaborative efforts between surgeons and eye banks have been at the core of advances that have been made in EK over the past decade. Corneal surgery starts in the eye bank, and it is important for corneal surgeons to understand the process and appreciate the efforts that have been made to provide them with suitable and safe donor corneal tissue.

Multimodal ocular imaging of known and novel corneal stromal disorders in dogs.

BACKGROUND: Imaging features obtained with Fourier-domain optical coherence tomography (FD-OCT) and in vivo confocal microscopy (IVCM) for corneal stromal disorders have been sparsely reported in dogs. This case report is a compilation of imaging features for three cases of different stromal disorders of the canine cornea which have not yet been reported elsewhere. CASE PRESENTATION: Lipid deposition in case 1 appeared as needle-shaped hyperreflective lines along the collagen lamellae, which correlated histologically with lipid clefts. In case 2, glycosaminoglycan accumulation by mucopolysaccharidosis type 1 caused diffuse stromal hyperreflectivity and depletion of keratocytes on IVCM and was associated with secondary corneal degeneration presumed to be calcium deposition. In case 3, posterior corneal stromal opacities in the absence of ocular inflammation were identified. Hyperreflective particles were scattered in the middle and posterior corneal stroma on FD-OCT. With IVCM, hyperreflective deposits were identified within keratocytes and the number of enlarged keratocytes containing hyperreflective deposits increased towards the posterior stroma. The bilateral, non-inflammatory nature and unique appearance with IVCM is most consistent with a posterior stromal dystrophy reminiscent of pre-Descemet corneal dystrophy described in humans. CONCLUSIONS: In vivo multimodal corneal imaging facilitated instantaneous microstructural analysis and may be valuable in the differential diagnosis of corneal stromal disorders in veterinary clinical practice. The non-specific nature of imaging findings occurs in some conditions such as mucopolysaccharidosis, thus in vivo corneal imaging should be complemented with other gold standard methods of definitive diagnosis.

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.

Autologous Serum-Based Eye Drops for Treatment of Ocular Surface Disease: A Report by the American Academy of Ophthalmology.

PURPOSE: To describe the safety and effectiveness of using autologous serum-based eye drops for the treatment of severe dry eye and persistent corneal epithelial defect. METHODS: Literature searches of the PubMed and Cochrane Library databases were conducted most recently in March 2019. The searches identified 281 citations, which were reviewed in abstract form. Of these, 48 were selected for a full-text review, and 13 met the inclusion criteria and were assigned a quality-of-evidence rating by the panel methodologist. Eight of these studies were rated level II and 5 were rated level III; there were no level I studies. RESULTS: This analysis included 10 studies of the use of autologous serum-based eye drops for severe dry eye disease and 4 studies of persistent epithelial defect. Several studies showed good effectiveness, with some improvement in symptoms, signs, or both. Eight of the studies reported improved symptoms for severe dry eye disease, and all noted improvement in at least 1 clinical sign. For persistent epithelial defects, all of the studies showed improvement, with 3 of the 4 demonstrating an improvement rate of more than 90%. Adverse events were rare. CONCLUSIONS: Although autologous serum-based tears may be effective in the treatment of severe dry eye and persistent epithelial defect, conclusions are limited owing to the absence of controlled trials.

Intraocular Lens Implantation in the Absence of Zonular Support: An Outcomes and Safety Update: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the visual acuity results and complications of different surgical techniques for intraocular lens (IOL) implantation in the absence of zonular support. METHODS: Peer-reviewed literature searches were conducted last in PubMed and the Cochrane Library in July 2019. The searches yielded 734 citations of articles published in English. The panel reviewed the abstracts of these mostly retrospective case series studies, and 45 were determined to be relevant to the assessment objectives. Three articles were rated as level II evidence, and 42 articles were rated as level III evidence. RESULTS: Eight different types of IOL fixation techniques with at least 6-month follow-up were evaluated: anterior chamber IOL (ACIOL), iris-claw IOL, retropupillary iris-claw IOL, 10-0 polypropylene iris-sutured posterior chamber IOL (PCIOL), 10-0 polypropylene scleral-sutured PCIOL, 8-0 polypropylene scleral-sutured PCIOL, CV-8 polytetrafluoroethylene, and intrascleral haptic fixation (ISHF). Eight articles reported data comparing 2 techniques. The 45 studies had insufficient statistical power to compare the techniques conclusively. A qualitative analysis of similar types showed that trends in visual acuity outcomes were not inferior to those of ACIOL implantation, but the severity of preoperative pathologic features was not controlled for. Compared with ACIOL, complications of cystoid macular edema were higher in 10-0 polypropylene iris-sutured PCIOL and 8-0 polypropylene scleral-sutured PCIOL. Non-anterior chamber IOL techniques were less likely to report chronic uveitis. Chronic glaucoma was highest in the 8-0 polypropylene scleral-sutured PCIOL group. Although retinal detachment was infrequent overall, it was twice as common in both iris- and scleral-sutured PCIOLs (except CV-8 polytetrafluoroethylene suture) compared with nonsutured methods: ACIOL, iris-clipped IOL, and ISHF PCIOL. CONCLUSIONS: The evidence reviewed shows no superiority of any single IOL implantation technique in the absence of zonular support. The various techniques seem to have equivalent visual acuity outcomes and safety profiles. Each technique has its own profile of inherent risk of postoperative complications. Surgeons must educate patients on the importance of close, long-term follow-up as a result of the uncertain nature of these techniques. Large prospective studies are needed to confirm the long-term complication profiles of these various IOL implantation techniques.

Descemet Membrane Endothelial Keratoplasty: Safety and Outcomes: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the safety and outcomes of Descemet membrane endothelial keratoplasty (DMEK) for the surgical treatment of corneal endothelial dysfunction. METHODS: Literature searches were last conducted in the PubMed and the Cochrane Library databases most recently in May 2017. The searches, which were limited to English-language abstracts, yielded 1085 articles. The panel reviewed the abstracts, and 47 were determined to be relevant to this assessment. RESULTS: After DMEK surgery, the mean best-corrected visual acuity (BCVA) ranged from 20/21 to 20/31, with follow-up ranging from 5.7 to 68 months. At 6 months, 37.6% to 85% of eyes achieved BCVA of 20/25 or better and 17% to 67% achieved BCVA of 20/20 or better. Mean endothelial cell (EC) loss was 33% (range, 25%-47%) at 6 months. Overall change in spherical equivalent was +0.43 diopters (D; range, -1.17 to +1.2 D), with minimal induced astigmatism of +0.03 D (range, -0.03 to +1.11 D). The most common complication was partial graft detachment requiring air injection (mean, 28.8%; range, 0.2%-76%). Intraocular pressure elevation was the second most common complication (range, 0%-22%) after DMEK, followed by primary graft failure (mean, 1.7%; range, 0%-12.5%), secondary graft failure (mean, 2.2%; range, 0%-6.3%), and immune rejection (mean, 1.9%; range, 0%-5.9%). Overall graft survival rates after DMEK ranged from 92% to 100% at last follow-up. Best-corrected visual acuity after Descemet's stripping endothelial keratoplasty (DSEK) ranged from 20/34 to 20/66 at 9 months. The most common complications after DSEK were graft detachment (mean, 14%; range, 0%-82%), endothelial rejection (mean, 10%; range, 0%-45%), and primary graft failure (mean, 5%; range, 0%-29%). Mean EC loss after DSEK was 37% at 6 months. CONCLUSIONS: The evidence reviewed supports DMEK as a safe and effective treatment for endothelial failure. With respect to visual recovery time, visual outcomes, and rejection rates, DMEK seems to be superior to DSEK and to induce less refractive error with similar surgical risks and EC loss compared with DSEK. The rate of air injection and repeat keratoplasty were similar in DMEK and DSEK after the learning curve for DMEK.

Herpes zoster ophthalmicus: acute keratitis.

PURPOSE OF REVIEW: Herpes zoster is a common condition, and involvement of the trigeminal nerve results in herpes zoster ophthalmicus (HZO). Acute keratitis is one of the most common of these ocular complications associated with HZO. The findings associated with and the management of acute zoster keratitis will be reviewed. RECENT FINDINGS: The incidence rate of herpes zoster has been on the rise over the past several decades. At the same time, the average patient age at presentation is declining with similar trends also seen in HZO. The cause of these changes has yet to be determined. Our understanding of corneal involvement in HZO continues to evolve with new imaging demonstrating viral particles within keratocytes in a case of zoster stromal keratitis. New medications such as topical ganciclovir are also helping to better manage acute zoster keratitis that is unresponsive to oral antiviral therapy. SUMMARY: Acute zoster keratitis can lead to permanent vision loss. Early diagnosis and management may help reduce these potentially devastating complications. Oral and topical antiviral medications can play a role in managing the acute disease, and herpes zoster vaccinations are important for prevention of disease. Further research must be done to establish standards for treatment of anterior segment complications from herpes zoster.

Biomechanical relationships between the corneal endothelium and Descemet's membrane.

The posterior face of the cornea consists of the corneal endothelium, a monolayer of cuboidal cells that secrete and attach to Descemet's membrane, an exaggerated basement membrane. Dysfunction of the endothelium compromises the barrier and pump functions of this layer that maintain corneal deturgesence. A large number of corneal endothelial dystrophies feature irregularities in Descemet's membrane, suggesting that cells create and respond to the biophysical signals offered by their underlying matrix. This review provides an overview of the bidirectional relationship between Descemet's membrane and the corneal endothelium. Several experimental methods have characterized a richly topographic and compliant biophysical microenvironment presented by the posterior surface of Descemet's membrane, as well as the ultrastructure and composition of the membrane as it builds during a lifetime. We highlight the signaling pathways involved in the mechanotransduction of biophysical cues that influence cell behavior. We present the specific example of Fuchs' corneal endothelial dystrophy as a condition in which a dysregulated Descemet's membrane may influence the progression of disease. Finally, we discuss some disease models and regenerative strategies that may facilitate improved treatments for corneal dystrophies.

Use of Scleral Lenses and Miniscleral Lenses After Penetrating Keratoplasty.

PURPOSE: To examine the clinical outcomes of scleral lenses for visual rehabilitation after penetrating keratoplasty (PK). METHODS: A retrospective review was conducted for 34 patients (48 eyes) who had a history of prior PK and were fit with scleral lenses between October 2009 and December 2013 at the UC Davis Eye Center. RESULTS: The most common initial indication for PK was keratoconus in 27 eyes (56%). Thirty-three eyes (69%) had previously been fit with other types of contact lenses, with small-diameter rigid gas-permeable lenses being the most common. The improvement in best-corrected visual acuity with a scleral lens compared with prior spectacle refraction or other contact lens was a mean of two best-corrected visual acuity lines. Forty-four eyes (91.7%) achieved functional vision with best scleral lens-corrected visual acuities of 20/40 or better. Patients who continued wearing scleral lenses were significantly more likely to report "good" subjective vision compared with patients who abandoned scleral lens wear (P=0.009), although change in objective best-corrected visual acuity did not differ significantly. There were no cases of infectious keratitis. Six eyes (12.5%) developed graft rejection; 3 were able to resume scleral lens wear. Nineteen eyes (39.5%) discontinued scleral lens wear for various reasons, the most common reason for discontinuation of lens wear was difficulty with scleral lens insertion or removal (8 eyes, 42.1%). CONCLUSION: Scleral lenses are effective and safe in patients who have had PK. There was a mean gain in visual acuity, with the majority of patients achieving 20/40 vision or better. The patient's subjective perception of vision was a significant factor in determining whether scleral lens wear was continued or abandoned.

Behavioral state and stimulus strength regulate the role of somatostatin interneurons in stabilizing network activity.

Inhibition stabilization enables cortical circuits to encode sensory signals across diverse contexts. Somatostatin-expressing (SST) interneurons are well-suited for this role through their strong recurrent connectivity with excitatory pyramidal cells. We developed a cortical circuit model predicting that SST cells become increasingly important for stabilization as sensory input strengthens. We tested this prediction in mouse primary visual cortex by manipulating excitatory input to SST cells, a key parameter for inhibition stabilization, with a novel cell-type specific pharmacological method to selectively block glutamatergic receptors on SST cells. Consistent with our model predictions, we find antagonizing glutamatergic receptors drives a paradoxical facilitation of SST cells with increasing stimulus contrast. In addition, we find even stronger engagement of SST-dependent stabilization when the mice are aroused. Thus, we reveal that the role of SST cells in cortical processing gradually switches as a function of both input strength and behavioral state.

Descemet Endothelial Thickness Comparison Trial 1 (DETECT 1): outcome masked, placebo-controlled trial comparing two types of corneal transplant surgeries and effect of rho kinase inhibitors on endothelial cell loss protocol.

BACKGROUND: It remains uncertain which endothelial keratoplasty (EK) technique yields the best outcomes while maintaining safety, particularly in eyes with coexisting ocular conditions. Moreover, the impact of endothelial cell loss (ECL) on long-term graft survival requires further investigation. Adjuvant ripasudil, a rho kinase inhibitor, may address the challenge of ECL in corneal transplantation. This paper presents the protocol for the Descemet Endothelial Thickness Comparison Trial 1 (DETECT 1), a multicentre, outcome-masked, randomised, placebo-controlled, four-arm clinical trial. METHODS: A total of 160 eligible patients with endothelial dysfunction will be enrolled from five participating sites in the USA. The patients will be randomly assigned in a 2×2 factorial design to one of the following treatment groups: group 1-ultrathin Descemet stripping endothelial keratoplasty (UT-DSAEK) plus topical ripasudil 0.4%; group 2-UT-DSAEK plus topical placebo; group 3-Descemet membrane endothelial keratoplasty (DMEK) plus topical ripasudil 0.4% and group 4-DMEK plus topical placebo. Primary outcomes include the best spectacle-corrected visual acuity at 12 months and ECL at 12 months. Secondary outcomes include visual acuity at different time points, vision-related quality of life, endothelial cell morphology and cost-effectiveness. RESULTS: The study outcomes will be analysed using mixed effects linear regression models, taking into account the treatment arms and relevant covariates. Adverse events, including rebubble procedures, graft failure and graft rejection, will be documented and analysed using appropriate statistical methods. CONCLUSION: DETECT I aims to provide evidence on the comparative effectiveness of UT-DSAEK and DMEK, as well as the potential benefits of adjuvant topical ripasudil in reducing ECL. The results of this trial will contribute to optimising corneal transplantation techniques and improving long-term graft survival, while also exploring the cost-effectiveness of these interventions. Dissemination of findings through peer-reviewed publications and national/international meetings will facilitate knowledge translation and guide clinical practice in the field of corneal transplantation. ETHICS AND DISSEMINATION: A data and safety monitoring committee (DSMC) has been empaneled by the NEI.All study protocols will be subject to review and approval by WCG IRB as the single IRB of record.This study will comply with the National Institute of Health (NIH) Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Data from the trial will be made available on reasonable request.

Descemet Endothelial Thickness Comparison Trial II (DETECT II): multicentre, outcome assessor-masked, placebo-controlled trial comparing Descemet membrane endothelial keratoplasty (DMEK) to Descemet stripping only (DSO) with adjunctive ripasudil for Fuchs dystrophy.

INTRODUCTION: It remains uncertain whether Descemet membrane endothelial keratoplasty (DMEK) or Descemet stripping only (DSO) yields better outcomes in patients with symptomatic Fuchs endothelial corneal dystrophy (FECD). This paper presents the protocol for the Descemet Endothelial Thickness Comparison Trial II (DETECT II), a multicentre, outcome-masked, randomised, placebo-controlled, clinical trial comparing DMEK to DSO with ripasudil (DSO-R) for this patient population. METHODS AND ANALYSIS: A total of 60 patients with endothelial dysfunction due to symptomatic FECD will be enrolled from seven participating sites in the USA. The patients will be randomly assigned in a 1:1 ratio to one of the following treatment groups: group 1-DMEK plus topical placebo and group 2-DSO plus topical ripasudil 0.4%. The enrolment period is 24 months. The primary outcome is best spectacle-corrected visual acuity at 12 months. Secondary outcomes include peripheral and central endothelial cell density, visual acuity, vision-related quality of life and Pentacam Scheimpflug tomography. Study outcomes will be analysed using mixed effects linear regression. Adverse events, including rebubble procedures, endothelial failure and graft rejection, will be documented and analysed using appropriate statistical methods. DETECT II aims to provide evidence on the comparative effectiveness of DMEK and DSO-R. The results of this trial will contribute to optimising the treatment of FECD, while also exploring the cost-effectiveness of these interventions. Dissemination of findings through peer-reviewed publications and national/international meetings will facilitate knowledge translation and guide clinical practice in the field of corneal transplantation. ETHICS AND DISSEMINATION: A data and safety monitoring committee has been empanelled by the National Eye Institute. All study protocols will be subject to review and approval by WCG IRB as the single IRB of record. This study will comply with the National Institute of Health (NIH) Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Data from the trial will be made available on reasonable request. TRIAL REGISTRATION NUMBER: NCT05275972.

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.

Catastrophic globe disruption as a result of a TASER injury.

BACKGROUND: Injuries caused by the TASER(®) (TASER International, Inc., Scottsdale, AZ) have been well documented, and both direct and indirect ocular injuries have been reported. We present a case of severe perforating injury to the globe from a TASER dart with central cornea penetration. OBJECTIVES: To describe the presentation and management of a penetrating ocular injury from a TASER dart. CASE REPORT: A 47-year-old woman presented with a TASER dart injury penetrating through the central cornea. The injury resulted in a stellate corneal laceration, which was repaired with a final visual acuity of light perception without projection. CONCLUSION: This is a case of a severe TASER-related ocular injury resulting in significant vision loss. Although mechanical trauma seemed to be the main etiology for vision loss, electrical shock injury may also be contributory. Direct injury to the eye from a TASER dart is similar to other perforating projectile injuries and can have a devastating visual outcome.

Input-specific synaptic depression shapes temporal integration in mouse visual cortex.

Efficient sensory processing requires the nervous system to adjust to ongoing features of the environment. In primary visual cortex (V1), neuronal activity strongly depends on recent stimulus history. Existing models can explain effects of prolonged stimulus presentation but remain insufficient for explaining effects observed after shorter durations commonly encountered under natural conditions. We investigated the mechanisms driving adaptation in response to brief (100 ms) stimuli in L2/3 V1 neurons by performing in vivo whole-cell recordings to measure membrane potential and synaptic inputs. We find that rapid adaptation is generated by stimulus-specific suppression of excitatory and inhibitory synaptic inputs. Targeted optogenetic experiments reveal that these synaptic effects are due to input-specific short-term depression of transmission between layers 4 and 2/3. Thus, brief stimulus presentation engages a distinct adaptation mechanism from that previously reported in response to prolonged stimuli, enabling flexible control of sensory encoding across a wide range of timescales.