Therapeutic Advances in Ophthalmology最新文献

Objective: Primary open-angle glaucoma (POAG) is a leading cause of vision loss, with lipid metabolism implicated in its pathogenesis. Our study explores lipid metabolism-derived acylation modifications in POAG using GEO, GWAS, and PubChem databases.

Methods: Integrated multi-omics approaches were employed: Mendelian randomization assessed causal relationships between lipid traits and POAG risk; transcriptomic analysis (gene set variation analysis, weighted gene co-expression network analysis) identified key acylation-related genes; machine learning selected feature genes; and single-cell sequencing validated mechanisms in human trabecular meshwork samples.

Results: Four lipid metabolism-derived acylations (palmitoylation, myristoylation, succinylation, malonylation) were significantly upregulated in POAG. Core genes 5'-aminolevulinate synthase 2 (ALAS2) and phospholipase C epsilon 1 (PLCE1) were mechanistically linked: ALAS2 catalyzed acyl-CoA accumulation, while myristoylated PLCE1 promoted trabecular fibrosis via collagen type IV alpha 3 chain interaction. External datasets confirmed these findings.

Conclusion: Lipid-derived acylations drive POAG through ALAS2-mediated acyl-CoA production and PLCE1-induced fibrosis, revealing novel targets for intervention. Lipid metabolism-derived acylation modifications, particularly succinylation, propionylation, and myristoylation, may play a crucial role in POAG. These findings highlight the potential role of acylation modifications in POAG and offer new insights into POAG's molecular mechanisms and potential research directions.

Background: Thyroid eye disease (TED) is an autoimmune inflammatory condition affecting the orbit and ocular surface, often leading to proptosis, diplopia, and evaporative dry eye. Tear film instability, eyelid retraction, and lagophthalmos contribute significantly to ocular surface dysfunction in TED. Smoking is a major risk factor that worsens disease severity and reduces treatment response.

Objectives: To evaluate ocular surface changes, treatment responses, and risk factors-including smoking-in patients with TED, and to assess the effects of different therapeutic modalities.

Design: Retrospective observational cohort study.

Methods: This retrospective study analyzed the records of 365 patients with TED followed between 2014 and 2021. Complete clinical data were available for 362 patients. Ocular parameters, including TBUT, OSDI, Oxford staining score, MRD-1, MRD-2, and Hertel exophthalmometry, were evaluated at baseline and follow-up. Treatment modalities included antithyroid drugs, corticosteroids, selenium supplementation, RAI, and surgery. Data were compared between smokers and nonsmokers.

Results: Among 362 patients (76% female), 105 (29%) were smokers. TED severity and persistent dry eye symptoms were significantly higher among smokers (p < 0.05). Posttreatment, significant improvements were observed in TBUT, OSDI, and Oxford scores (p < 0.05). Selenium supplementation showed potential benefit. CAS decreased significantly over follow-up (from 7.7% to 4.7% active cases, p < 0.05). TED progression was observed in 18.7% of patients receiving RAI therapy. Surgical intervention rates were low.

Conclusion: TED causes notable ocular surface dysfunction and dry eye symptoms, particularly in smokers. Medical and surgical treatments provide effective disease control, while selenium appears promising for disease stabilization. Smoking cessation and early multidisciplinary management are critical to improving outcomes.

Glaucoma, a leading global cause of irreversible blindness, often progresses despite adequate intraocular pressure (IOP) control, highlighting a crucial unmet need for neuroprotective strategies that directly promote retinal ganglion cell survival. In addition, the glaucoma standard of care is often reactive, initiating only on measurable structural or functional loss and lacking in structured, proactive approach to neuroprotection. This review introduces the NP-10 System, a novel conceptual framework designed to systematically address 10 diverse and interrelated neuroprotective mechanisms implicated in glaucomatous neurodegeneration. Broadly, these can be categorized as pressure-related factors (direct IOP and psychological stress), vascular factors (encompassing vascular dysregulation and homocysteine-related endothelial dysfunction), cellular dysfunctions (mitochondrial dysfunction, glycolysis impairment, oxidative stress, and chronic inflammation), and functional deficits (macular pigment deficiency and impaired axonal function). Specific nutraceutical interventions, including saffron, French maritime pine, bilberry, palmitoylethanolamide, nicotinamide, methylfolate, methylcobalamin, macular carotenoids, Ginkgo biloba, pyruvate, and citicoline, may target multiple mechanisms to reduce IOP, modulate stress, improve ocular perfusion, enhance cellular bioenergetics, provide antioxidant and anti-inflammatory benefits, augment macular pigment, and improve visual function in glaucoma. With promising emerging evidence for neuroprotection, the NP-10 System provides a scaffold for future large, randomized trials to establish clinical efficacy, optimize formulations, and clarify safety profiles of these nutraceuticals, paving the way for integrating targeted nutritional support into proactive glaucoma care.

Neonatal retinal hemorrhage (RH) and retinopathy of prematurity (ROP) are significant causes of visual impairment in preterm infants, necessitating effective diagnostic and therapeutic strategies. This review synthesizes current approaches to RH and ROP management, highlighting their limitations and the critical need for standardized diagnostic criteria. Indirect ophthalmoscopy, while accessible, suffers from subjective variability, whereas wide-field digital retinal imaging, despite superior visualization, is limited by cost and training requirements. Vaginal delivery and prematurity-related factors, such as fragile retinal vasculature and neonatal complications (e.g., sepsis and hyperbilirubinemia), significantly increase RH and ROP risk, with severe RH correlating with ROP progression. Advances in digital retinal imaging and artificial intelligence (AI) offer promising solutions for early detection, enabling timely interventions such as anti-VEGF therapy to improve visual outcomes. Future directions include developing universal diagnostic standards, exploring novel treatments such as probiotics, and leveraging technologies such as optical coherence tomography. Enhanced screening programs, collaborative research, and public awareness are essential to optimize RH and ROP management, ultimately improving long-term visual prognosis for affected infants.

This study evaluated the effectiveness of topical losartan 1 mg/mL in reducing corneal fibrosis by inhibiting myofibroblast proliferation and improving corneal transparency, offering a potential therapeutic alternative. A prospective, interventional case series enrolled adults with corneal fibrosis. Participants administered topical losartan 1 mg/mL six times daily for 3 months. Visual acuity, slit-lamp examination, corneal tomography, and densitometry were used to assess outcomes. A Random Forest machine learning model identified key predictors of visual improvement. Nineteen eyes from seventeen patients were analyzed. Mean uncorrected distance visual acuity improved from 1.04 ± 0.62 to 0.74 ± 0.46 LogMAR (p = 0.007). Corneal densitometry significantly decreased, particularly in the midperipheral zone (p = 0.0184). Worse baseline visual acuity and longer leukoma duration correlated with greater improvement. The predictive model achieved an AUROC of 0.76, with 86.67% sensitivity, 75.00% specificity, and 84.21% accuracy, confirming its robustness. These findings suggest that topical losartan improves corneal transparency and functional vision in patients with corneal fibrosis. The predictive model provides a clinically useful scoring system to guide treatment selection. Further validation in larger clinical trials is warranted.

Purpose: Corneal high-order aberrations due to pterygium have a significant impact on patients' visual quality. This study aims to assess changes in corneal high-order aberrations following pterygium surgery.

Methods: This hospital-based prospective study included 51 eyes of 51 patients with primary pterygium who underwent pterygium excision with conjunctival autograft. Corneal topography and ocular high-order aberrations (HOA) were measured using corneal topography and aberrometry scans with a Sirius Scheimpflug-Placido topographer, both preoperatively and 6 weeks postoperatively. These values were derived for both 3 and 5 mm pupillary diameters using Zernike polynomial expansion. The relative risk of residual postoperative aberrations was assessed in relation to increasing pterygium size.

Results: The mean age of patients enrolled in the study was 40.3 ± 7.4 years. The root mean square value of total HOA significantly decreased at 6 weeks after uneventful pterygium surgery. Excision of pterygium significantly reduced all parameters (coma: 95% CI, p < 0.05; trefoil: 95% CI, p < 0.05; quadrafoil: 95% CI, p < 0.05), with trefoil being the main contributor. Astigmatism values also showed a significant postoperative reduction. In 15.9% of patients, preoperative "with-the-rule astigmatism" changed to postoperative "against-the-rule astigmatism." A notable increase in the relative risk of residual postoperative HOA was observed when the pterygium length exceeded 4 mm.

Conclusion: Pterygia are associated with corneal higher-order aberrations, particularly trefoil, which were largely eliminated by surgery. Earlier excision of pterygia reduces the likelihood of significant residual aberrations.

Background: Retinal implants have emerged as interventions to partially restore functional vision such as light perception, motion detection or object localisation in patients with severe vision loss from degenerative retinal conditions, including retinitis pigmentosa (RP) and dry age-related macular degeneration (AMD).

Objectives: To evaluate the long-term efficacy, safety and quality of life (QoL) impact of retinal implants with ⩾1 year of follow-up.

Methods: Following PRISMA guidelines, a systematic search was conducted (31st July to 31st August 2024) in Web of Science, PubMed, Medline, Scopus, Cochrane Library and Embase, using the terms: ('retinal implant' OR 'retinal prosthesis') AND ('long-term' OR 'follow-up') AND ('efficacy' OR 'safety' OR 'quality of life'). No publication date restrictions were applied. Eligible studies were in English, involved human subjects with retinal degenerations, and reported ⩾1 year follow-up. Risk of bias was assessed using the Critical Appraisal Skills Programme (CASP) cohort study checklist for most studies, as they involved prospective follow-up without randomisation or control groups. The Joanna Briggs Institute (JBI) critical appraisal checklist for case series was applied to studies with a case series design. Narrative synthesis was applied.

Results: Thirteen studies met the inclusion criteria: 53.85% assessed epiretinal implants (Argus II), 30.77% subretinal (Alpha AMS and PRIMA), and 15.38% suprachoroidal (44 and 49-channel STS). Epiretinal implants improved visual function, with up to 89% better in SLT, 50%-56% in DOM, and 30%-40% reaching ⩾2.9 logMAR when activated. Subretinal implants enhanced light perception, localisation, and grating acuity (to 3.33 cycles/degree), with acuity of 20/460 and 20/550 in some cases. Suprachoroidal devices improved SLT, DOM and GVA. Adverse events were more frequent with epiretinal than other implant types. QoL outcomes improved, particularly in mobility, orientation, and daily tasks.

Conclusion: Retinal implants confer functional vision, but acuities remain below 20/200, and recipients continue to meet criteria for legal blindness. Given the high risk of bias, lack of controls and potential placebo effects, further high-quality evidence is needed to confirm their efficacy, safety and QoL impact.

Rituximab, an anti-CD-20 monoclonal antibody, has garnered increasing interest as a therapeutic option in orbital inflammatory disease (OID). We report our institutional experience with intralesional rituximab injections in two cases of orbital granulomatosis with polyangiitis (GPA), and additionally review the literature surrounding intralesional rituximab in OID. Two patients (a 74-year-old male (Case 1) and a 63-year-old female (Case 2)) with orbital GPA received intralesional rituximab injections at our tertiary institution. Case 1 had evidence of left optic neuropathy in extensive bilateral inferomedial orbital inflammation, while Case 2 had severe refractory and relapsing left orbital inflammation. Both patients received intralesional rituximab injections (Riximyo 10 mg/ml), administered weekly over 8-11 weeks. Rituximab injections were adjunctive to systemic induction therapy, including corticosteroids and rituximab infusion in Case 1, and a course of corticosteroids only in Case 2. Both patients demonstrated a clinico-radiological response to treatment. In conclusion, we present our experience with intralesional rituximab injections, used as an adjunctive treatment modality for orbital GPA, in a case of optic neuropathy and another of severe, refractory, and relapsing disease. Further prospective studies are required to define its utility and the long-term outcomes of intralesional rituximab injections in OID.

Background/objectives: To evaluate the effect of macular status and fixation, as determined by chord alpha, on refractive outcomes following combined phacovitrectomy for retinal detachment. Although an optical biometer can be used to calculate the required dioptric power of the intraocular lens, loss of central fixation can introduce errors into the biometric parameters.

Design: Retrospective single-center observational study.

Methods: Patients with retinal detachment and cataract who underwent combined phacoemulsification and vitrectomy following swept-source optical coherence tomography-based biometry (ZEISS IOLMaster 700) were included, and their preoperative macular status, chord-alpha length, and resulting refractive error at the final follow-up appointment were recorded.

Results: A total of 305 eyes were evaluated, of which 150 had macular detachment. There was a statistically significantly higher rate of refractive error in eyes with macular detachment compared to eyes without (p < 0.001). Absolute refractive prediction error of more than 1 diopter was found in 31% of eyes with detached maculae, compared to 12% of eyes without macular involvement. Eyes with a detached macula showed a significantly longer chord alpha (right eye: p = 0.01; left eye: p < 0.0001), and linear regression analysis revealed that a longer chord alpha was associated with a myopic refractive error. The presence of other factors that also correlated with refractive error underscores the multifactorial pathogenesis of refractive prediction error.

Conclusions: Compared to non-macular involvement, macular detachment led to worse refractive outcomes in combined phacovitrectomy, and chord alpha, as a marker for central fixation, might serve as an explanation. Further research is needed to determine whether combined phacoemulsification and vitrectomy should be performed in patients with macular detachment.

Background: Facial masks are essential for preventing respiratory infections, particularly among healthcare workers. However, prolonged mask use may lead to ocular surface disruption, known as mask-associated dry eye (MADE).

Objectives: To evaluate the impact of different types of disposable surgical masks on tear film parameters and corneal wavefront aberrations during an 8-h work shift.

Design: Randomized clinical trial.

Methods: Sixty healthcare personnel at Rajavithi Hospital were randomly assigned to three mask groups: Group 1 (earloop surgical mask; Medimask^®), Group 2 (earloop surgical mask with adhesive nose strip), and Group 3 (anti-fog earloop surgical mask; Welcare 3D Blue Line Anti-Fog Mask^®). Non-invasive tear breakup time (NIBUT), tear meniscus height (TMH), and conjunctival redness were assessed using the Oculus Keratograph^®5M. Corneal higher-order aberrations (HOAs) were measured using the GALILEI Dual Scheimpflug Analyzer before and after 8 h of mask wear.

Results: TMH decreased significantly in all groups: Group 1 from 201.13 ± 85.10 µm to 174.53 ± 42.01 µm (p = 0.003), Group 2 from 188.81 ± 59.55 µm to 164.61 ± 50.58 µm (p = 0.036), and Group 3 from 194.50 ± 58.29 µm to 166.25 ± 45.90 µm (p = 0.034). NIBUT showed slight, non-significant decreases: Group 1 (9.26 ± 4.47-8.35 ± 3.26 s), Group 2 (8.88 ± 3.79-8.20 ± 3.12 s), and Group 3 (9.14 ± 4.20-8.55 ± 3.74 s). Conjunctival redness increased significantly only in Group 1 (1.75 ± 0.47-1.98 ± 0.52, p = 0.048). HOAs were mostly unchanged, except for total HOAs at the 6 mm zone, which were higher in Group 3 (1.85 ± 1.20) than in Group 1 (1.14 ± 0.48) and Group 2 (1.28 ± 0.58; p = 0.012).

Conclusion: An 8-h shift of mask use reduced TMH across all groups and increased conjunctival redness in earloop surgical masks without adhesive. Although most optical aberrations remained unchanged, elevated HOAs in the anti-fog earloop surgical mask group may affect vision quality under mesopic conditions.

Thai clinical trials registry: TCTR 20230725002 (https://www.thaiclinicaltrials.org/show/TCTR20230725002).