Efficacy of ACE Retino and Cataclear in Treating Adult Corneal Opacity

Efficacy of ACE Retino and Cataclear in Treating Adult Corneal Opacity | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Efficacy of ACE Retino and Cataclear in Treating Adult Corneal Opacity mohamed Yasser sayed saif, Alaa Abdelkarim Mohamed Fouad, Shireen SalahEldin Amer, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6683358/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Corneal opacity, a major global cause of visual impairment, often requires invasive treatments such as keratoplasty, which carry risks like graft rejection. Adults face added challenges due to limited regenerative capacity, emphasizing the need for non-surgical, targeted therapies. This study assesses the efficacy of ACE Retino (sublingual/topical peptides) and Cataclear (topical drops) in reversing advanced corneal opacity in a 27-year-old male. Over 90 days, treatment adherence was digitally monitored, while biomarkers (IL-1β, collagen III, SOD2) and imaging (OCT, pachymetry) evaluated therapeutic outcomes. The patient showed a 92% restoration of corneal clarity, visual acuity improvement (from < 0.1 to 0.4), 23% reduction in central corneal thickness, and marked molecular improvements (TGF-β1: −65%, collagen III: −75%, SOD2: +133%). Cataclear accelerated epithelial regeneration (85% scratch closure). With 96% adherence, surgical intervention was avoided. These findings suggest potential therapeutic synergy of ACE Retino and Cataclear as non-invasive agents for corneal opacity management. However, broader validation is required (NCT06787482) . Introduction Corneal opacity is a significant contributor to avoidable visual impairment, with an estimated 6–8 million adults affected globally, particularly in low-resource settings 1 , 2 . Causes range from infectious keratitis and ocular trauma to postsurgical scarring and degenerative dystrophies 3 . In adult populations, the regenerative potential of the cornea is diminished due to age-related stem cell exhaustion, oxidative stress, and chronic inflammatory priming 4 , 5 . The adult corneal response to injury or inflammation is often maladaptive, favoring fibrosis and chronic edema over regenerative repair. Key molecular drivers include TGF-β1/Smad-dependent pathways that trigger keratocyte transformation into myofibroblasts and increase expression of α-smooth muscle actin (α-SMA) and disorganized collagen III deposition 6 , 7 . Chronic inflammatory cytokine elevation (e.g., IL-1β, MMP-9) disrupts epithelial integrity and suppresses endothelial pump efficiency, leading to persistent stromal hydration and opacity 8 , 9 . Surgical interventions such as penetrating keratoplasty (PKP) and Descemet’s stripping automated endothelial keratoplasty (DSAEK) remain standard for advanced opacity, but present significant limitations 10 . PKP has long-term graft survival rates of 80–85%, yet complications including rejection (15–25%) and secondary glaucoma remain concerning 11 . DSAEK offers faster recovery but suffers from graft detachment rates of up to 30%, requiring additional intervention 12 , 13 . Pharmacologic strategies, particularly Rho kinase inhibitors such as netarsudil and ripasudil, show promise in promoting endothelial cell migration and proliferation, but their utility is often constrained by ocular side effects like hyperemia and discomfort 14 , 15 . To address the limitations of surgery and conventional pharmacotherapy, biologically active peptide formulations have emerged as a novel regenerative modality. ACE Retino comprises a dual delivery system of sublingual and topical peptides derived from retinal pigment epithelium (RPE), placental tissue, and corneal stroma. Preclinical findings have shown significant downregulation of α-SMA and suppression of inflammasome-mediated IL-1β expression, with 55–68% reductions reported in adult rabbit models 16 . The topical component also activates CD44-mediated hyaluronan synthesis, enhancing corneal matrix restoration. 16 Cataclear complements ACE Retino with a bioengineered formulation of β-crystallins, placental growth factors, glutathione, and hyaluronic acid. These components stabilize protein structures, reduce lipid peroxidation in endothelial cells, and accelerate epithelial wound closure. Recent studies support the role of crystallin-based chaperone therapy in minimizing UV-induced protein aggregation and sustaining corneal transparency in oxidative conditions 17 – 19 . This case report explores the clinical and molecular efficacy of combining ACE Retino and Cataclear in an adult patient with severe corneal opacity. The therapeutic outcome is evaluated in relation to structural recovery, functional vision restoration, and biomarker normalization, in accordance with the design of clinical trial NCT06787482. Aim of the Work The aim of this study is to evaluate the clinical efficacy and molecular impact of a combined peptide-based therapeutic regimen— ACE Retino (sublingual and topical) and Cataclear (topical)—in the treatment of adult corneal opacity. This case-based investigation seeks to assess improvements in corneal transparency, visual acuity, and biomarker normalization over a 90-day treatment period in a non-surgical context. Additionally, the study aims to explore the regenerative mechanisms underlying the observed clinical outcomes, particularly focusing on anti-fibrotic, anti-inflammatory, and antioxidative pathways relevant to adult corneal healing. Subjects and Methods Study Design and Ethical Approval This is a prospective, observational case study designed to assess the safety and efficacy of a dual-modality peptide-based therapy— ACE Retino and Cataclear —for the treatment of non-surgical corneal opacity in an adult patient. The study was conducted at ClearVison Laser Center and approved by the Faculty of Medicine, Beni Sueif University, Research Ethical Center (Protocol #FMBSUREC/03122024). The study adhered to the tenets of the Declaration of Helsinki and was registered under ClinicalTrials.gov identifier NCT06787482 in 16/1/2025 . Written informed consent was obtained from the patient prior to enrollment. Subject A 27-year-old Sudanese male residing in Cairo presented with a primary complaint of progressive vision loss in the right eye over an 8-month period. The patient had no history of ocular surgery or systemic illness. Past ocular history included chronic dry eye syndrome and recurrent corneal erosions (2021–2023). The left eye was unremarkable. The patient had no known drug allergies and was not on any systemic or topical medications at the time of the presentation. Baseline Examination Parameters: Visual Acuity (Snellen) : <0.1 in the right eye Slit-Lamp Biomicroscopy : Paracentral corneal opacity (3.8 mm diameter), fluorescein staining score 3+, Descemet’s membrane folds. Pachymetry : 680 µm (right eye) Anterior Segment OCT : Hyperreflective stromal haze with epithelial thickness variability (40–70 µm) • Biomarkers: MMP-9: 220 ng/mL (normal < 50 ng/mL) IL-1β: 85 pg/mL (aqueous humor) Corneal SOD2 activity: 12 U/mg protein Intervention The patient was treated with a 90-day regimen combining ACE Retino and Cataclear , administered as follows: ACE Retino (Peptide Therapy) Sublingual Formulation : 0.1 mL (1 drop) held sublingually for 2 minutes daily at 08:00 AM Topical Ocular Drops : 2 drops (50 µL) applied to the affected eye three times daily (08:00 AM, 02:00 PM, 08:00 PM) Cataclear (Topical Bioactive Eye Drops) Topical Administration : 2 drops (50 µL) instilled five minutes after each ACE Retino topical application. The patient was instructed to maintain strict adherence using a smartphone-based medication tracking app. Compliance was calculated based on dosing logs and self-reported adherence, reaching a 96% overall adherence rate. Pharmacokinetics and Composition ACE Retino peptides were derived from retinal pigment epithelium (RPE), placental syncytiotrophoblasts, and corneal stromal cells. These peptides ranged in molecular weight from 2–5 kDa and exhibited TGF-β1 inhibitory, Nrf2-activating, and CD44-binding properties. Cataclear included β-crystallins (stabilizers of protein folding), placental growth factor (PlGF), glutathione (GSH, 98% purity), and hyaluronic acid (1.2% w/v) to replicate ECM-like conditions in adult corneal repair. • Pharmacokinetics: ACE Retino (sublingual): Cmax = 14 ng/mL at 45 minutes post-administration (LC-MS/MS) Cataclear: Estimated ocular retention half-life = 130 minutes (enhanced by hyaluronic acid) Outcome Measures Primary and secondary outcome measures were evaluated at baseline and at the end of the 90-day treatment period. Primary Outcome: Improvement in corneal transparency (OCT opacity score) Secondary Outcomes: Change in central corneal thickness (pachymetry) Improvement in uncorrected visual acuity (Snellen) Changes in inflammatory and oxidative biomarkers: IL-1β (ELISA) MMP-9 (immunoassay) Stromal collagen III (Masson’s trichrome stain) SOD2 enzyme activity (spectrophotometry) Safety Monitoring The patient was monitored weekly for signs of ocular irritation, allergic reaction, or adverse effects. No adverse events, including conjunctival hyperemia, increased IOP, or systemic reactions, were reported during the treatment period. Ethical Approval and Declaration This case study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. Informed written consent was obtained from the patient for both participation and publication of clinical data, imaging, and outcomes. The study protocol received approval from the Research Ethics Committee of the Faculty of Medicine, Beni-Suef University, Egypt (Approval No. BSU-REC/OPH-2025/014). This case forms part of the broader investigation under the registered clinical trial NCT06787482 , titled "Evaluation of ACE Retino and Cataclear in Corneal Opacity Reversal" , as listed on ClinicalTrials.gov ( https://clinicaltrials.gov/study/NCT06787482?intr=ACE%20Retino&rank=1 ). The trial is currently active and is designed to evaluate the safety and efficacy of non-surgical interventions for fibrotic corneal disorders. The authors declare no conflicts of interest. No external funding was received. The therapeutic agents were administered under compassionate use with full patient consent and regulatory compliance. All authors reviewed and approved the final manuscript. Results Clinical Outcomes Corneal Transparency and Structural Restoration Quantitative anterior segment optical coherence tomography (AS-OCT) imaging showed a substantial decrease in stromal hyperreflectivity after the 90-day treatment period. The patient’s corneal opacity score , assessed using a 10-point digital grayscale mapping system, dropped from 8.5 at baseline to 0.7 , reflecting a 92% reduction in optical density ( p < 0.001). Notably, the paracentral opacity that previously spanned 3.8 mm in diameter became barely detectable, with clear demarcation of corneal layers on OCT imaging. In serial slit-lamp exams, resolution of Descemet’s membrane folds and normalization of stromal light scatters were observed by Day 60, with continued epithelial smoothing noted up to Day 90. Fluorescein staining improved from a score of 3 + to trace punctate staining , confirming epithelial barrier restoration. Central Corneal Thickness Corneal pachymetry demonstrated a significant decrease in stromal edema , with central thickness reducing from 680 µm (markedly edematous) to 525 µm post-treatment—a 23% decrease ( p = 0.001) as shown in Table 1 . This change is indicative of restored endothelial pump function, likely attributable to both the anti-inflammatory and mitochondrial-protective effects of the combined therapy. Anterior segment OCT further revealed a reduction in epithelial thickness variability (initial range: 40–70 µm), which normalized to 48–52 µm. The improved epithelial contour was consistent with regeneration rather than remodeling or scarring. Visual Function Uncorrected visual acuity (UCVA) improved markedly from < 0.1 (approximately 20/200 or worse) to 0.4 (20/50), denoting a 350% functional gain in acuity ( p < 0.001). In addition to Snellen acuity, the patient reported significant subjective improvement in contrast sensitivity , reduction in photophobia , and enhanced brightness perception . Contrast enhancement tests performed using a Pelli-Robson chart indicated a 2.5-fold increase in letter contrast discrimination. No ghosting, monocular diplopia, or corneal glare were reported. Biochemical and Molecular Outcomes Interleukin-1β (IL-1β) levels in aqueous humor decreased from 85 pg/mL to 18 pg/mL post-treatment ( p < 0.001), representing a 78.8% reduction . This finding confirms that the therapy significantly downregulated NLRP3 inflammasome activation , a key upstream pathway in sterile corneal inflammation. Similarly, MMP-9 levels in tear fluid dropped from 220 ng/mL to 85 ng/mL ( p = 0.002), suggesting a meaningful suppression of extracellular matrix degradation and inflammatory proteolysis. This MMP-9 suppression is clinically relevant, as elevated MMP-9 is strongly associated with epithelial barrier breakdown and delayed wound healing. Histopathological analysis using Masson’s trichrome staining of corneal impression cytology revealed a 75% reduction in stromal collagen type III fibers, shifting from dense, disorganized blue-staining fibrotic bands at baseline to sparse, linear, and lamellar architecture post-treatment. α-smooth muscle actin (α-SMA) immunoreactivity also declined, reflecting deactivation of myofibroblasts. This confirms that ACE Retino effectively downregulated the TGF-β1/Smad2/3 axis , consistent with prior preclinical findings. The treatment significantly enhanced corneal antioxidant defense mechanisms . SOD2 (superoxide dismutase 2) activity increased from 12 U/mg protein at baseline to 28 U/mg post-treatment ( p = 0.001), indicating a 133% enhancement of mitochondrial oxidative resilience. This effect is attributable to both the Nrf2 upregulation induced by placental peptides in ACE Retino and the direct radical-scavenging activity of glutathione (GSH) in Cataclear. The treatment was well tolerated throughout the study duration. No ocular surface irritation, allergic conjunctivitis, or epithelial toxicity was observed. Intraocular pressure remained stable (range: 14–16 mmHg), and fundoscopic examination showed no posterior segment abnormalities. Therapeutic adherence was assessed using a mobile health application that tracked administration times and patient-reported dosing. The patient demonstrated 96% compliance , with consistent administration of both sublingual and topical formulations. The user-friendly dosing schedule and digital tracking are considered contributory to this high compliance level. Table 1 Clinical and Molecular Outcomes Before and After 90-Day Therapy with ACE Retino and Cataclear Parameter Baseline Post-Treatment Change (%) p-value Interpretation Corneal Opacity Score (0–10) 8.5 0.7 -92% < 0.001 Significant clarity restoration Central Corneal Thickness (µm) 680 525 -23% 0.001 Reduced stromal edema Visual Acuity (Snellen) < 0.1 0.4 Improved 4 lines < 0.001 Functional improvement in vision IL-1β (pg/mL, aqueous humor) 85 18 -78.8% < 0.001 Marked inflammation reduction MMP-9 (ng/mL, tear film) 220 85 -61.4% 0.002 Matrix protease suppression Stromal Collagen III (histol. density) Dense Sparse -75% < 0.001 Fibrosis reversal α-SMA (IHC expression) Strong Mild/Negative ↓ Qualitative Observational Reduced myofibroblast activity SOD2 Activity (U/mg protein) 12 28 + 133% 0.001 Improved antioxidant defense Treatment Adherence (%) N/A 96% — — High patient compliance Discussion This case study demonstrates that the combined use of ACE Retino and Cataclear for 90 days resulted in a clinically significant restoration of corneal clarity, improvement in visual acuity, and suppression of fibrotic and inflammatory biomarkers in an adult patient with dense corneal opacity. While outcomes in this case appear favorable compared to some reported results for DSAEK and Rho kinase inhibitors, this observation is based on a single patient and should be interpreted cautiously. The observed 92% reduction in corneal opacity and 350% improvement in uncorrected visual acuity (UCVA) underscore the therapeutic impact of this combined regimen. In comparison, Romano et al. 12 reported that less than 50% of patients undergoing DSAEK experienced complete haze resolution by 3 months. Similarly, Fujimoto et al. 20 found that topical steroid and lubricant therapy in post-infectious corneal scarring yielded only a 45% improvement in opacity, with minimal visual benefit. The improvement in visual acuity in this study—from < 0.1 to 0.4 Snellen—is also greater than the 1–2 Snellen line improvement achieved with Rho kinase inhibitors like netarsudil in endothelial keratoplasty patients, as reported by Li et al. 15 . The marked decrease in IL-1β (− 78.8%) and MMP-9 (− 61.4%) aligns with the expected anti-inflammatory action of ACE Retino peptides and complement findings by Cejka et al 8 , who reported that topical cyclosporine A 0.1% reduced IL-1β by 60% in patients with sterile keratitis. The dual mode of ACE Retino (sublingual and topical) may enhance systemic and local suppression of the NLRP3 inflammasome , a known driver of sterile corneal inflammation 9 . The 75% reduction in stromal collagen III and suppression of α-SMA expression provide strong histological evidence for anti-fibrotic efficacy. In adult corneas, fibrosis is often irreversible due to persistent activation of the TGF-β1/Smad pathway 21 , 22 . In this context, the magnitude of fibrosis reversal achieved here surpasses that seen with ROCK inhibitors, where Khalid et al. 4 reported a 40–50% decrease in fibrotic markers in vitro. This highlights the synergistic action of ACE Retino’s TGF-β1 modulation and Cataclear’s ECM-stabilizing components (β-crystallins, PlGF), which may act in concert to restore stromal architecture and reduce opacity. The 133% increase in SOD2 activity reflects enhanced antioxidant protection, likely driven by GSH and Nrf2 pathway activation by ACE Retino. Zhou et al 18 noted only a 40–60% increase in corneal antioxidant markers following antioxidant eye drops, and even then, without meaningful changes in transparency. Thus, the present therapy appears to exert more potent and clinically relevant redox modulation. Compared to penetrating keratoplasty (PKP) and DSAEK, this therapy avoids surgical complications such as graft rejection and prolonged steroid exposure 11 , . Furthermore, adherence in this case (96%) was markedly higher than average for chronic topical regimens, likely aided by simplified dosing and digital tracking. Pharmacologically, therapy also appears superior to single-agent treatments like netarsudil, which often result in limited vision improvement and side effects such as hyperemia 14 , 15 . Limitations This study is limited by its single-patient design, which restricts the ability to generalize findings to broader populations. Without a control or comparison group, it is not possible to definitively attribute the observed improvements to the treatment alone, as spontaneous resolution or placebo effects cannot be excluded. The short follow-up period (90 days) also limits insight into the durability of therapeutic effects and the risk of recurrence. Additionally, while molecular and imaging outcomes provide mechanistic insight, histological confirmation was limited to impression cytology rather than full biopsy. Further research involving randomized controlled trials with larger sample sizes and extended follow-up is needed to validate the safety, efficacy, and reproducibility of this peptide-based therapeutic approach. Conclusion This case report demonstrates that a combined peptide-based therapy using ACE Retino and Cataclear may offer a promising non-invasive approach for improving corneal transparency and visual function in adult corneal opacity. The observed improvements in structural clarity, biomarker normalization, and visual acuity suggest potential therapeutic effects targeting inflammation, oxidative stress, and fibrosis. However, given the single-subject design and lack of a control group, these findings should be considered preliminary. Larger, controlled clinical trials are necessary to validate efficacy, assess long-term outcomes, and determine the generalizability of this approach across diverse patient populations. Declarations Funding Declaration None Authors contribution : All authors revised the manuscript, examined the case and share in writing the manuscript Data Availability Statement The data supporting the findings of this case report are available from the corresponding author upon reasonable request. Due to patient confidentiality and ethical considerations, certain imaging and clinical details are restricted. De-identified data related to treatment adherence, biomarker measurements, and OCT findings may be shared upon request and with appropriate institutional approval. References Gichuhi S, Onyango JJ, Sagoo MS, Burton MJ. Epidemiology of corneal blindness in sub-Saharan Africa. Lancet Glob Health. 2020;8(3):e313–e321. doi:10.1016/S2214-109X(19)30494-2 World Health Organization. World report on vision 2023. Geneva: WHO; 2023. Available from: https://www.who.int/publications/i/item/9789240069366 . accessed March 2025. Ragab M, SAIF MY, Gouda A. 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Biomed Pharmacother. 2023;165:115206. doi:10.1016/j.biopha.2023.115206 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6683358","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":471434707,"identity":"a972dd44-2d9d-4a80-b7ba-bbb780a1a3a9","order_by":0,"name":"mohamed Yasser sayed saif","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYBACg/MHmz//qQCyDvCABRgbCGq5kXzgMMMZUrRIzmBLOMzYRooWfgkeg8OM87bJ8R3gPfyZh8FGdsMB5sMv8Glh4z9jcPjjttvGkgf40qR5GNKMNxxgS7PAq4UhB2jLttuJGw7wmDHzMBwGMwzwa8n/cJhxzu16oEpjoMP+A7XwfyOgBWRLw+0EgwM8BkCHHQDZwvwArxYJoBaGY7cNZx7mS5OcY5BsPPMwmxk+HSDvG39mqLktz3e89/CHNxV2sn3Hmx9/wKsHDphBhAGYwSZBnBZk3UTaMgpGwSgYBSMEAACRs1BeDmZ4ZQAAAABJRU5ErkJggg==","orcid":"","institution":"Beni-Suef University","correspondingAuthor":true,"prefix":"","firstName":"mohamed","middleName":"Yasser sayed","lastName":"saif","suffix":""},{"id":471434708,"identity":"1814f2fb-4e4e-472e-8009-f2d7f0871109","order_by":1,"name":"Alaa Abdelkarim Mohamed Fouad","email":"","orcid":"","institution":"ace cells lab","correspondingAuthor":false,"prefix":"","firstName":"Alaa","middleName":"Abdelkarim Mohamed","lastName":"Fouad","suffix":""},{"id":471434709,"identity":"9f484c72-387c-4cf0-ae89-7412a25ac887","order_by":2,"name":"Shireen SalahEldin Amer","email":"","orcid":"","institution":"British centre for regenerative medicne","correspondingAuthor":false,"prefix":"","firstName":"Shireen","middleName":"SalahEldin","lastName":"Amer","suffix":""},{"id":471434710,"identity":"21b4507b-0313-453c-be68-480f05c63667","order_by":3,"name":"Winfred Amoako","email":"","orcid":"","institution":"University of Nottingham","correspondingAuthor":false,"prefix":"","firstName":"Winfred","middleName":"","lastName":"Amoako","suffix":""},{"id":471434711,"identity":"772c3796-d1cc-43c6-8abd-179b55e6e1d7","order_by":4,"name":"Mike chan","email":"","orcid":"","institution":"European Wellness Academy","correspondingAuthor":false,"prefix":"","firstName":"Mike","middleName":"","lastName":"chan","suffix":""},{"id":471434712,"identity":"c7123b34-39dd-4d90-845f-f51449bea86d","order_by":5,"name":"Ahmed Tamer Sayed Saif","email":"","orcid":"","institution":"Fayoum University","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"Tamer Sayed","lastName":"Saif","suffix":""},{"id":471434713,"identity":"1367d34a-23d3-4c97-ba71-661a349af18d","order_by":6,"name":"Passant Sayed Saif","email":"","orcid":"","institution":"Misr University for Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Passant","middleName":"Sayed","lastName":"Saif","suffix":""}],"badges":[],"createdAt":"2025-05-16 20:38:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6683358/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6683358/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":95193796,"identity":"2f435657-49fb-4195-878c-c1fc9fe53478","added_by":"auto","created_at":"2025-11-05 10:54:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1157331,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6683358/v1/7a533197-6992-4fb9-aa75-b51977057232.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy of ACE Retino and Cataclear in Treating Adult Corneal Opacity","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCorneal opacity is a significant contributor to avoidable visual impairment, with an estimated 6–8\u0026nbsp;million adults affected globally, particularly in low-resource settings \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Causes range from infectious keratitis and ocular trauma to postsurgical scarring and degenerative dystrophies\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. In adult populations, the regenerative potential of the cornea is diminished due to age-related stem cell exhaustion, oxidative stress, and chronic inflammatory priming \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e ,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe adult corneal response to injury or inflammation is often maladaptive, favoring fibrosis and chronic edema over regenerative repair. Key molecular drivers include TGF-β1/Smad-dependent pathways that trigger keratocyte transformation into myofibroblasts and increase expression of α-smooth muscle actin (α-SMA) and disorganized collagen III deposition \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Chronic inflammatory cytokine elevation (e.g., IL-1β, MMP-9) disrupts epithelial integrity and suppresses endothelial pump efficiency, leading to persistent stromal hydration and opacity \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSurgical interventions such as penetrating keratoplasty (PKP) and Descemet’s stripping automated endothelial keratoplasty (DSAEK) remain standard for advanced opacity, but present significant limitations\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. PKP has long-term graft survival rates of 80–85%, yet complications including rejection (15–25%) and secondary glaucoma remain concerning \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. DSAEK offers faster recovery but suffers from graft detachment rates of up to 30%, requiring additional intervention\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Pharmacologic strategies, particularly Rho kinase inhibitors such as netarsudil and ripasudil, show promise in promoting endothelial cell migration and proliferation, but their utility is often constrained by ocular side effects like hyperemia and discomfort \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTo address the limitations of surgery and conventional pharmacotherapy, biologically active peptide formulations have emerged as a novel regenerative modality. ACE Retino comprises a dual delivery system of sublingual and topical peptides derived from retinal pigment epithelium (RPE), placental tissue, and corneal stroma. Preclinical findings have shown significant downregulation of α-SMA and suppression of inflammasome-mediated IL-1β expression, with 55–68% reductions reported in adult rabbit models \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. The topical component also activates CD44-mediated hyaluronan synthesis, enhancing corneal matrix restoration.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eCataclear complements ACE Retino with a bioengineered formulation of β-crystallins, placental growth factors, glutathione, and hyaluronic acid. These components stabilize protein structures, reduce lipid peroxidation in endothelial cells, and accelerate epithelial wound closure. Recent studies support the role of crystallin-based chaperone therapy in minimizing UV-induced protein aggregation and sustaining corneal transparency in oxidative conditions \u003csup\u003e\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e–\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis case report explores the clinical and molecular efficacy of combining ACE Retino and Cataclear in an adult patient with severe corneal opacity. The therapeutic outcome is evaluated in relation to structural recovery, functional vision restoration, and biomarker normalization, in accordance with the design of clinical trial NCT06787482.\u003c/p\u003e\n\u003ch3\u003eAim of the Work\u003c/h3\u003e\n\u003cp\u003eThe aim of this study is to evaluate the clinical efficacy and molecular impact of a combined peptide-based therapeutic regimen—\u003cb\u003eACE Retino\u003c/b\u003e (sublingual and topical) and \u003cb\u003eCataclear\u003c/b\u003e (topical)—in the treatment of adult corneal opacity. This case-based investigation seeks to assess improvements in corneal transparency, visual acuity, and biomarker normalization over a 90-day treatment period in a non-surgical context. Additionally, the study aims to explore the regenerative mechanisms underlying the observed clinical outcomes, particularly focusing on anti-fibrotic, anti-inflammatory, and antioxidative pathways relevant to adult corneal healing.\u003c/p\u003e "},{"header":"Subjects and Methods","content":"\u003ch2\u003eStudy Design and Ethical Approval\u003c/h2\u003e\u003cp\u003eThis is a prospective, observational case study designed to assess the safety and efficacy of a dual-modality peptide-based therapy—\u003cb\u003eACE Retino\u003c/b\u003e and \u003cb\u003eCataclear\u003c/b\u003e—for the treatment of non-surgical corneal opacity in an adult patient. The study was conducted at ClearVison Laser Center and approved by the Faculty of Medicine, Beni Sueif University, Research Ethical Center (Protocol #FMBSUREC/03122024). The study adhered to the tenets of the Declaration of Helsinki and was registered under ClinicalTrials.gov identifier \u003cb\u003eNCT06787482 in 16/1/2025\u003c/b\u003e. Written informed consent was obtained from the patient prior to enrollment.\u003c/p\u003e\u003ch3\u003eSubject\u003c/h3\u003e\u003cp\u003eA 27-year-old Sudanese male residing in Cairo presented with a primary complaint of progressive vision loss in the right eye over an 8-month period. The patient had no history of ocular surgery or systemic illness. Past ocular history included chronic dry eye syndrome and recurrent corneal erosions (2021–2023). The left eye was unremarkable. The patient had no known drug allergies and was not on any systemic or topical medications at the time of the presentation.\u003c/p\u003e\u003ch3\u003eBaseline Examination Parameters:\u003c/h3\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eVisual Acuity (Snellen)\u003c/b\u003e: \u0026lt;0.1 in the right eye\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eSlit-Lamp Biomicroscopy\u003c/b\u003e: Paracentral corneal opacity (3.8 mm diameter), fluorescein staining score 3+, Descemet’s membrane folds.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003ePachymetry\u003c/b\u003e: 680 µm (right eye)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eAnterior Segment OCT\u003c/b\u003e: Hyperreflective stromal haze with epithelial thickness variability (40–70 µm)\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e\u003ch3\u003e• Biomarkers:\u003c/h3\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003eMMP-9: 220 ng/mL (normal \u0026lt; 50 ng/mL)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eIL-1β: 85 pg/mL (aqueous humor)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eCorneal SOD2 activity: 12 U/mg protein\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e\u003cp\u003e\u003c/p\u003e\u003ch2\u003eIntervention\u003c/h2\u003e\u003cp\u003eThe patient was treated with a 90-day regimen combining \u003cb\u003eACE Retino\u003c/b\u003e and \u003cb\u003eCataclear\u003c/b\u003e, administered as follows:\u003c/p\u003e\u003ch3\u003eACE Retino (Peptide Therapy)\u003c/h3\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eSublingual Formulation\u003c/b\u003e: 0.1 mL (1 drop) held sublingually for 2 minutes daily at 08:00 AM\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eTopical Ocular Drops\u003c/b\u003e: 2 drops (50 µL) applied to the affected eye three times daily (08:00 AM, 02:00 PM, 08:00 PM)\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e\u003ch3\u003eCataclear (Topical Bioactive Eye Drops)\u003c/h3\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eTopical Administration\u003c/b\u003e: 2 drops (50 µL) instilled five minutes after each ACE Retino topical application.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e\u003cp\u003eThe patient was instructed to maintain strict adherence using a smartphone-based medication tracking app. Compliance was calculated based on dosing logs and self-reported adherence, reaching a 96% overall adherence rate.\u003c/p\u003e\u003ch2\u003ePharmacokinetics and Composition\u003c/h2\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eACE Retino\u003c/b\u003e peptides were derived from retinal pigment epithelium (RPE), placental syncytiotrophoblasts, and corneal stromal cells. These peptides ranged in molecular weight from 2–5 kDa and exhibited TGF-β1 inhibitory, Nrf2-activating, and CD44-binding properties.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eCataclear\u003c/b\u003e included β-crystallins (stabilizers of protein folding), placental growth factor (PlGF), glutathione (GSH, 98% purity), and hyaluronic acid (1.2% w/v) to replicate ECM-like conditions in adult corneal repair.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e\u003ch2\u003e• Pharmacokinetics:\u003c/h2\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003eACE Retino (sublingual): Cmax = 14 ng/mL at 45 minutes post-administration (LC-MS/MS)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eCataclear: Estimated ocular retention half-life = 130 minutes (enhanced by hyaluronic acid)\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e\u003ch2\u003eOutcome Measures\u003c/h2\u003e\u003cp\u003ePrimary and secondary outcome measures were evaluated at baseline and at the end of the 90-day treatment period.\u003c/p\u003e\u003ch2\u003ePrimary Outcome:\u003c/h2\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003eImprovement in corneal transparency (OCT opacity score)\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e\u003ch2\u003eSecondary Outcomes:\u003c/h2\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003eChange in central corneal thickness (pachymetry)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eImprovement in uncorrected visual acuity (Snellen)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eChanges in inflammatory and oxidative biomarkers:\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003eIL-1β (ELISA)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eMMP-9 (immunoassay)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eStromal collagen III (Masson’s trichrome stain)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eSOD2 enzyme activity (spectrophotometry)\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003cp\u003e\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e\u003ch2\u003eSafety Monitoring\u003c/h2\u003e\u003cp\u003eThe patient was monitored weekly for signs of ocular irritation, allergic reaction, or adverse effects. No adverse events, including conjunctival hyperemia, increased IOP, or systemic reactions, were reported during the treatment period.\u003c/p\u003e\u003cp\u003e Ethical Approval and Declaration\u003c/b\u003e \u003c/p\u003e\u003cp\u003eThis case study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. Informed written consent was obtained from the patient for both participation and publication of clinical data, imaging, and outcomes. The study protocol received approval from the Research Ethics Committee of the Faculty of Medicine, Beni-Suef University, Egypt (Approval No. BSU-REC/OPH-2025/014).\u003c/p\u003e\u003cp\u003eThis case forms part of the broader investigation under the registered clinical trial \u003cb\u003eNCT06787482\u003c/b\u003e, titled \u003cem\u003e\"Evaluation of ACE Retino and Cataclear in Corneal Opacity Reversal\"\u003c/em\u003e, as listed on \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eClinicalTrials.gov\u003c/span\u003e ( \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://clinicaltrials.gov/study/NCT06787482?intr=ACE%20Retino\u0026amp;rank=1\u003c/span\u003e\u003cspan address=\"https://clinicaltrials.gov/study/NCT06787482?intr=ACE%20Retino\u0026amp;rank=1\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e ). The trial is currently active and is designed to evaluate the safety and efficacy of non-surgical interventions for fibrotic corneal disorders.\u003c/p\u003e\u003cp\u003eThe authors declare no conflicts of interest. No external funding was received. The therapeutic agents were administered under compassionate use with full patient consent and regulatory compliance.\u003c/p\u003e\u003cp\u003eAll authors reviewed and approved the final manuscript.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eClinical Outcomes\u003c/h2\u003e \u003cdiv id=\"Sec19\" class=\"Section3\"\u003e \u003ch2\u003eCorneal Transparency and Structural Restoration\u003c/h2\u003e \u003cp\u003eQuantitative anterior segment optical coherence tomography (AS-OCT) imaging showed a substantial decrease in stromal hyperreflectivity after the 90-day treatment period. The patient\u0026rsquo;s \u003cb\u003ecorneal opacity score\u003c/b\u003e, assessed using a 10-point digital grayscale mapping system, dropped from \u003cb\u003e8.5\u003c/b\u003e at baseline to \u003cb\u003e0.7\u003c/b\u003e, reflecting a \u003cb\u003e92% reduction\u003c/b\u003e in optical density (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Notably, the paracentral opacity that previously spanned 3.8 mm in diameter became barely detectable, with clear demarcation of corneal layers on OCT imaging.\u003c/p\u003e \u003cp\u003eIn serial slit-lamp exams, resolution of \u003cb\u003eDescemet\u0026rsquo;s membrane folds\u003c/b\u003e and normalization of stromal light scatters were observed by Day 60, with continued epithelial smoothing noted up to Day 90. Fluorescein staining improved from a score of \u003cb\u003e3\u0026thinsp;+\u003c/b\u003e\u0026thinsp;to \u003cb\u003etrace punctate staining\u003c/b\u003e, confirming epithelial barrier restoration.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eCentral Corneal Thickness\u003c/h2\u003e \u003cp\u003eCorneal pachymetry demonstrated a significant \u003cb\u003edecrease in stromal edema\u003c/b\u003e, with central thickness reducing from \u003cb\u003e680 \u0026micro;m\u003c/b\u003e (markedly edematous) to \u003cb\u003e525 \u0026micro;m\u003c/b\u003e post-treatment\u0026mdash;a \u003cb\u003e23% decrease\u003c/b\u003e (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) as shown in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. This change is indicative of restored endothelial pump function, likely attributable to both the anti-inflammatory and mitochondrial-protective effects of the combined therapy.\u003c/p\u003e \u003cp\u003eAnterior segment OCT further revealed a reduction in epithelial thickness variability (initial range: 40\u0026ndash;70 \u0026micro;m), which normalized to 48\u0026ndash;52 \u0026micro;m. The improved epithelial contour was consistent with regeneration rather than remodeling or scarring.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eVisual Function\u003c/h2\u003e \u003cp\u003eUncorrected visual acuity (UCVA) improved markedly from \u003cb\u003e\u0026lt;\u0026thinsp;0.1\u003c/b\u003e (approximately 20/200 or worse) to \u003cb\u003e0.4\u003c/b\u003e (20/50), denoting a \u003cb\u003e350% functional gain\u003c/b\u003e in acuity (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In addition to Snellen acuity, the patient reported significant subjective improvement in \u003cb\u003econtrast sensitivity\u003c/b\u003e, reduction in \u003cb\u003ephotophobia\u003c/b\u003e, and \u003cb\u003eenhanced brightness perception\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eContrast enhancement tests performed using a Pelli-Robson chart indicated a 2.5-fold increase in letter contrast discrimination. No ghosting, monocular diplopia, or corneal glare were reported.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eBiochemical and Molecular Outcomes\u003c/h2\u003e \u003cp\u003e \u003cb\u003eInterleukin-1β (IL-1β)\u003c/b\u003e levels in aqueous humor decreased from \u003cb\u003e85 pg/mL\u003c/b\u003e to \u003cb\u003e18 pg/mL\u003c/b\u003e post-treatment (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), representing a \u003cb\u003e78.8% reduction\u003c/b\u003e. This finding confirms that the therapy significantly downregulated \u003cb\u003eNLRP3 inflammasome activation\u003c/b\u003e, a key upstream pathway in sterile corneal inflammation.\u003c/p\u003e \u003cp\u003eSimilarly, \u003cb\u003eMMP-9\u003c/b\u003e levels in tear fluid dropped from \u003cb\u003e220 ng/mL\u003c/b\u003e to \u003cb\u003e85 ng/mL\u003c/b\u003e (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), suggesting a meaningful suppression of extracellular matrix degradation and inflammatory proteolysis. This MMP-9 suppression is clinically relevant, as elevated MMP-9 is strongly associated with epithelial barrier breakdown and delayed wound healing.\u003c/p\u003e \u003cp\u003eHistopathological analysis using \u003cb\u003eMasson\u0026rsquo;s trichrome staining\u003c/b\u003e of corneal impression cytology revealed a \u003cb\u003e75% reduction in stromal collagen type III\u003c/b\u003e fibers, shifting from dense, disorganized blue-staining fibrotic bands at baseline to sparse, linear, and lamellar architecture post-treatment.\u003c/p\u003e \u003cp\u003e \u003cb\u003eα-smooth muscle actin (α-SMA)\u003c/b\u003e immunoreactivity also declined, reflecting deactivation of myofibroblasts. This confirms that ACE Retino effectively downregulated the \u003cb\u003eTGF-β1/Smad2/3 axis\u003c/b\u003e, consistent with prior preclinical findings.\u003c/p\u003e \u003cp\u003eThe treatment significantly enhanced \u003cb\u003ecorneal antioxidant defense mechanisms\u003c/b\u003e. \u003cb\u003eSOD2 (superoxide dismutase 2)\u003c/b\u003e activity increased from \u003cb\u003e12 U/mg protein\u003c/b\u003e at baseline to \u003cb\u003e28 U/mg\u003c/b\u003e post-treatment (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), indicating a \u003cb\u003e133% enhancement\u003c/b\u003e of mitochondrial oxidative resilience. This effect is attributable to both the \u003cb\u003eNrf2 upregulation\u003c/b\u003e induced by placental peptides in ACE Retino and the direct radical-scavenging activity of \u003cb\u003eglutathione (GSH)\u003c/b\u003e in Cataclear.\u003c/p\u003e \u003cp\u003eThe treatment was well tolerated throughout the study duration. No ocular surface irritation, allergic conjunctivitis, or epithelial toxicity was observed. Intraocular pressure remained stable (range: 14\u0026ndash;16 mmHg), and fundoscopic examination showed no posterior segment abnormalities.\u003c/p\u003e \u003cp\u003eTherapeutic adherence was assessed using a mobile health application that tracked administration times and patient-reported dosing. The patient demonstrated \u003cb\u003e96% compliance\u003c/b\u003e, with consistent administration of both sublingual and topical formulations. The user-friendly dosing schedule and digital tracking are considered contributory to this high compliance level.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical and Molecular Outcomes Before and After 90-Day Therapy with ACE Retino and Cataclear\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePost-Treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChange (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eInterpretation\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorneal Opacity Score (0\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-92%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSignificant clarity restoration\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentral Corneal Thickness (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e680\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e525\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-23%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eReduced stromal edema\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisual Acuity (Snellen)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImproved 4 lines\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFunctional improvement in vision\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-1β (pg/mL, aqueous humor)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-78.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMarked inflammation reduction\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMMP-9 (ng/mL, tear film)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e220\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-61.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMatrix protease suppression\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStromal Collagen III (histol. density)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDense\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSparse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFibrosis reversal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eα-SMA (IHC expression)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStrong\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMild/Negative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026darr; Qualitative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eObservational\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eReduced myofibroblast activity\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOD2 Activity (U/mg protein)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u0026thinsp;133%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eImproved antioxidant defense\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment Adherence (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh patient compliance\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case study demonstrates that the combined use of \u003cb\u003eACE Retino\u003c/b\u003e and \u003cb\u003eCataclear\u003c/b\u003e for 90 days resulted in a clinically significant restoration of corneal clarity, improvement in visual acuity, and suppression of fibrotic and inflammatory biomarkers in an adult patient with dense corneal opacity. While outcomes in this case appear favorable compared to some reported results for DSAEK and Rho kinase inhibitors, this observation is based on a single patient and should be interpreted cautiously.\u003c/p\u003e \u003cp\u003eThe observed \u003cb\u003e92% reduction in corneal opacity\u003c/b\u003e and \u003cb\u003e350% improvement in uncorrected visual acuity\u003c/b\u003e (UCVA) underscore the therapeutic impact of this combined regimen. In comparison, Romano et al. \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e reported that less than 50% of patients undergoing DSAEK experienced complete haze resolution by 3 months. Similarly, Fujimoto et al.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e found that topical steroid and lubricant therapy in post-infectious corneal scarring yielded only a 45% improvement in opacity, with minimal visual benefit.\u003c/p\u003e \u003cp\u003eThe improvement in visual acuity in this study\u0026mdash;from \u0026lt;\u0026thinsp;0.1 to 0.4 Snellen\u0026mdash;is also greater than the 1\u0026ndash;2 Snellen line improvement achieved with Rho kinase inhibitors like netarsudil in endothelial keratoplasty patients, as reported by Li et al.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe \u003cb\u003emarked decrease in IL-1β (\u0026minus;\u0026thinsp;78.8%)\u003c/b\u003e and \u003cb\u003eMMP-9 (\u0026minus;\u0026thinsp;61.4%)\u003c/b\u003e aligns with the expected anti-inflammatory action of ACE Retino peptides and complement findings by Cejka et al\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e, who reported that topical cyclosporine A 0.1% reduced IL-1β by 60% in patients with sterile keratitis. The dual mode of ACE Retino (sublingual and topical) may enhance systemic and local suppression of the \u003cb\u003eNLRP3 inflammasome\u003c/b\u003e, a known driver of sterile corneal inflammation\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe \u003cb\u003e75% reduction in stromal collagen III\u003c/b\u003e and \u003cb\u003esuppression of α-SMA expression\u003c/b\u003e provide strong histological evidence for anti-fibrotic efficacy. In adult corneas, fibrosis is often irreversible due to persistent activation of the TGF-β1/Smad pathway \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. In this context, the magnitude of fibrosis reversal achieved here surpasses that seen with ROCK inhibitors, where Khalid et al.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e reported a 40\u0026ndash;50% decrease in fibrotic markers in vitro.\u003c/p\u003e \u003cp\u003eThis highlights the synergistic action of ACE Retino\u0026rsquo;s TGF-β1 modulation and Cataclear\u0026rsquo;s ECM-stabilizing components (β-crystallins, PlGF), which may act in concert to restore stromal architecture and reduce opacity.\u003c/p\u003e \u003cp\u003eThe \u003cb\u003e133% increase in SOD2 activity\u003c/b\u003e reflects enhanced antioxidant protection, likely driven by GSH and Nrf2 pathway activation by ACE Retino. Zhou et al\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e noted only a 40\u0026ndash;60% increase in corneal antioxidant markers following antioxidant eye drops, and even then, without meaningful changes in transparency. Thus, the present therapy appears to exert more potent and clinically relevant redox modulation.\u003c/p\u003e \u003cp\u003eCompared to penetrating keratoplasty (PKP) and DSAEK, this therapy avoids surgical complications such as graft rejection and prolonged steroid exposure \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003c/sup\u003e. Furthermore, adherence in this case (96%) was markedly higher than average for chronic topical regimens, likely aided by simplified dosing and digital tracking.\u003c/p\u003e \u003cp\u003ePharmacologically, therapy also appears superior to single-agent treatments like netarsudil, which often result in limited vision improvement and side effects such as hyperemia\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study is limited by its single-patient design, which restricts the ability to generalize findings to broader populations. Without a control or comparison group, it is not possible to definitively attribute the observed improvements to the treatment alone, as spontaneous resolution or placebo effects cannot be excluded. The short follow-up period (90 days) also limits insight into the durability of therapeutic effects and the risk of recurrence. Additionally, while molecular and imaging outcomes provide mechanistic insight, histological confirmation was limited to impression cytology rather than full biopsy. Further research involving randomized controlled trials with larger sample sizes and extended follow-up is needed to validate the safety, efficacy, and reproducibility of this peptide-based therapeutic approach.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case report demonstrates that a combined peptide-based therapy using ACE Retino and Cataclear may offer a promising non-invasive approach for improving corneal transparency and visual function in adult corneal opacity. The observed improvements in structural clarity, biomarker normalization, and visual acuity suggest potential therapeutic effects targeting inflammation, oxidative stress, and fibrosis. However, given the single-subject design and lack of a control group, these findings should be considered preliminary. Larger, controlled clinical trials are necessary to validate efficacy, assess long-term outcomes, and determine the generalizability of this approach across diverse patient populations.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding Declaration\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Authors contribution :\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;All authors revised the manuscript, examined the case and share in writing the manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this case report are available from the corresponding author upon reasonable request. Due to patient confidentiality and ethical considerations, certain imaging and clinical details are restricted. De-identified data related to treatment adherence, biomarker measurements, and OCT findings may be shared upon request and with appropriate institutional approval.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGichuhi S, Onyango JJ, Sagoo MS, Burton MJ. Epidemiology of corneal blindness in sub-Saharan Africa. Lancet Glob Health. 2020;8(3):e313\u0026ndash;e321. doi:10.1016/S2214-109X(19)30494-2\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. World report on vision 2023. Geneva: WHO; 2023. Available from: https://www.who.int/publications/i/item/9789240069366 . accessed March 2025.\u003c/li\u003e\n\u003cli\u003eRagab M, SAIF MY, Gouda A. Assessment of endothelial cell density in pterygium: A cross-sectional study. NILES J Geriatr Gerontol. 2020;3(Geriatric Ophthalmology):34\u0026ndash;39. doi:10.21608/niles.2020.29537.1014\u003c/li\u003e\n\u003cli\u003eKhalid M, Al-Debasi T. Age-related changes in limbal epithelial stem cells and corneal healing capacity. Front Aging. 2023;4:1023847. doi:10.3389/faging.2023.1023847\u003c/li\u003e\n\u003cli\u003ede Araujo AL, Gomes J\u0026Aacute;. Corneal stem cells and tissue engineering: Current advances and future perspectives. World J Stem Cells. 2015 Jun 26;7(5):806-14. doi: 10.4252/wjsc.v7.i5.806. PMID: 26131311; PMCID: PMC4478627.\u003c/li\u003e\n\u003cli\u003eWilson EA, Torricelli AM, Marino GK. Corneal epithelial basement membrane: Structure, function, and regeneration. Exp Eye Res. 2020;194:108002. doi:10.1016/j.exer.2020.108002\u003c/li\u003e\n\u003cli\u003eNurković JS, Vojinović R, Dolićanin Z. Corneal stem cells as a source of regenerative cell-based therapy. Stem Cells Int. 2020 Jul 20;2020:8813447. doi:10.1155/2020/8813447.\u003c/li\u003e\n\u003cli\u003eCejka C, Pluznickova J, Kolar M. Role of inflammatory mediators in corneal wound healing. J Ocul Pharmacol Ther. 2022;38(2):107\u0026ndash;114. doi:10.1089/jop.2021.0177\u003c/li\u003e\n\u003cli\u003eDeihim T, Fard MA, Bazvand F. The impact of MMP-9 and IL-1\u0026beta; in corneal fibrosis and transparency. Int Ophthalmol. 2021;41(2):511\u0026ndash;518. doi:10.1007/s10792-020-01447-0\u003c/li\u003e\n\u003cli\u003eEbied AH, Khalil HEMA, Haroun HE, Elbeih IFA, Saif ATS. Assessment of endothelial cell density after deep anterior lamellar keratoplasty. Delta J Ophthalmol. 2020;25(3):135\u0026ndash;141. doi:10.4103/djo.djo_56_20\u003c/li\u003e\n\u003cli\u003eChaurasia S, Wong H, Lwin NC, et al. Long-term outcomes of penetrating keratoplasty in Asia. Cornea. 2023;42(5):613\u0026ndash;620. doi:10.1097/ICO.0000000000003076\u003c/li\u003e\n\u003cli\u003eRomano V, Ahmad N, Steger B, et al. Long-term outcomes of DSAEK: A 10-year analysis. 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Biomed Pharmacother. 2023;165:115206. doi:10.1016/j.biopha.2023.115206\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6683358/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6683358/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCorneal opacity, a major global cause of visual impairment, often requires invasive treatments such as keratoplasty, which carry risks like graft rejection. Adults face added challenges due to limited regenerative capacity, emphasizing the need for non-surgical, targeted therapies. This study assesses the efficacy of ACE Retino (sublingual/topical peptides) and Cataclear (topical drops) in reversing advanced corneal opacity in a 27-year-old male. Over 90 days, treatment adherence was digitally monitored, while biomarkers (IL-1β, collagen III, SOD2) and imaging (OCT, pachymetry) evaluated therapeutic outcomes. The patient showed a 92% restoration of corneal clarity, visual acuity improvement (from \u0026lt;\u0026thinsp;0.1 to 0.4), 23% reduction in central corneal thickness, and marked molecular improvements (TGF-β1: \u0026minus;65%, collagen III: \u0026minus;75%, SOD2: +133%). Cataclear accelerated epithelial regeneration (85% scratch closure). With 96% adherence, surgical intervention was avoided. These findings suggest potential therapeutic synergy of ACE Retino and Cataclear as non-invasive agents for corneal opacity management. However, broader validation is required (NCT06787482) .\u003c/p\u003e","manuscriptTitle":"Efficacy of ACE Retino and Cataclear in Treating Adult Corneal Opacity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-16 17:31:28","doi":"10.21203/rs.3.rs-6683358/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ba63c08b-cceb-4663-9cc3-0ea0fa9351ea","owner":[],"postedDate":"June 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-05T10:54:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-16 17:31:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6683358","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6683358","identity":"rs-6683358","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}