Ophthalmology and Therapy最新文献

Introduction: In congenital aniridia caused by mutations in paired box 6 (PAX6), PAX6 influences the migration and differentiation of limbal epithelial cells (LECs), thereby playing a pivotal role in aniridia-associated keratopathy. The antidepressants ritanserin and duloxetine affect PAX6 expression in LECs. Limbal stromal cells, which support limbal epithelial stem cells, are crucial in the limbal stem cell niche. This study explores how ritanserin and duloxetine influence gene expression in primary human limbal stromal cells from subjects with congenital aniridia and from healthy subjects, in vitro.

Methods: Primary human limbal stromal cells from corneas affected by aniridia (AN-LSCs) (n = 8) and from healthy corneas (LSCs) (n = 8) were isolated and cultured in either low-glucose serum-free (LGSF) or normal-glucose serum-containing (NGSC) media. Cells were treated with 4 µM ritanserin or duloxetine for 24 h. Quantitative PCR (qPCR) and western blot were used to assess the expression of PAX6, FOSL2, TGF-β1, ACTA2A1, LUM, COL1A1, COL5A1, DSG1, FABP5 and ADH7.

Results: In AN-LSCs with LGSF-medium, ritanserin increased PAX6 messenger RNA (mRNA) (p = 0.007) and decreased TGF-β1 and FOSL2 mRNA levels (P = 0.005, P = 0.038). In addition, TGF-β1 protein levels decreased with both treatments (P = 0.02, P = 0.007), and FABP5 protein level increased, using ritanserin (P = 0.019). In LSCs with LGSF-medium, ACTA2A1 mRNA levels decreased using ritanserin and duloxetine (P = 0.028; P = 0.031), while FABP5 mRNA levels increased with ritanserin treatment (P = 0.003). Also, duloxetine use reduced α-SMA protein (P = 0.013) and increased FABP5 protein levels (P = 0.029). In LSCs with NGSC-medium, ritanserin elevated LUM, FABP5 and ADH7 mRNA and protein levels (P = 0.025, P = 0.003, P = 0.047, P = 0.024, P = 0.013, P = 0.039).

Conclusions: The results of our study confirmed that the antipsychotropic drugs ritanserin and duloxetine alter PAX6 and TGF-β1 gene expression in AN-LSCs cultured in LGSF-medium. These drugs were found to have an impact on retinoic acid signaling pathways and keratocyte characteristic markers both in LSCs and AN-LSCs, using different culture media.

Introduction: The aim of this study was to investigate the predictive factors for persistent disease activity following anti-vascular endothelial growth factors (anti-VEGF) and their long-term effects in patients to be treated for neovascular age-related macular degeneration (nAMD) under real-world conditions.

Methods: Retrospective data analysis of the PROOF study, a multi-center real-world retrospective chart review conducted across Korea in patients with nAMD included treatment-naive patients with nAMD who received first anti-VEGF (ranibizumab, bevacizumab, or aflibercept) between January 2017 and March 2019 was performed. All 600 patients (cohort 1) had a minimum follow-up of 12 months of which 453 patients (cohort 2) were followed-up for 24 months from baseline.

Results: At month 12 after anti-VEGF therapy, 58.10% (95% confidence interval [CI]: 54.09, 62.12) of patients and at month 24, 66.02% of patients continued to have persistent retinal fluid. At both months 12 and 24, predictive factors for persistent disease activity were fibrovascular pigment epithelial detachments (PED) (P = 0.0494) and retinal fluid at month 3 after loading phase (P = 0.0082). The mean changes in visual acuity were + 6.2, + 10.1, and + 13.3 letters and in the central subfield thickness were - 79.1 µm, - 96.3 µm, and - 134.4 µm at 12 months from baseline, in the bevacizumab, aflibercept, and ranibizumab groups, respectively.

Conclusions: The presence of retinal fluid after loading phase and fibrovascular PED were predictors of persistent disease activity after at least 1 year of anti-VEGF treatment.

Introduction: This study assessed the efficacy, durability, and safety of faricimab in patients with neovascular age-related macular degeneration (nAMD), previously treated with aflibercept or ranibizumab with unsatisfactory results.

Methods: This was a single-center, prospective cohort study of all consecutive patients with nAMD switched to intravitreally administered faricimab from traditional anti-vascular endothelial growth factor (anti-VEGF) treatments between September 2022 and April 2023 because of unsatisfactory response (maximal fluid-free interval ≤ 8 weeks). Faricimab was administered with a loading dose of four 4-weekly injections, followed by a treat-and-extend regimen. The primary outcome measures were maximum fluid-free interval after the switch and last assigned treatment interval. Secondary outcome measures included best-corrected visual acuity (BCVA) and structural optical coherence tomography parameters.

Results: Thirty-three eyes of 33 patients were included. Patients were followed for a median of 72 weeks [interquartile range 61, 76]. Median maximum fluid-free treatment interval after switch to faricimab and the last assigned interval were significantly longer than before the switch (7 vs. 4 weeks, p < 0.001 and 8 vs. 5 weeks, p < 0.001, respectively). Significant improvements in central subfield thickness (353 vs. 281 µm), macular volume (2.46 vs. 2.16 mm³), and pigment epithelial detachment height (198 vs. 150 µm) were observed (all p < 0.001). BCVA remained stable at 0.4 versus 0.3 logMAR before switch (p = 0.190). One eye (3%) developed intraocular inflammation and one eye (3%) developed a retinal pigment epithelium tear.

Conclusions: Faricimab improved anatomical outcomes and allowed longer treatment intervals in patients with nAMD previously treated with other anti-VEGF therapies with unsatisfactory response, reducing treatment burden. A favorable safety profile was observed.

Introduction: To investigate the impact of posterior vitreous detachment (PVD) on the risk of developing neovascular glaucoma (NVG) in eyes with occlusions of the retinal artery (RAO) or retinal vein (RVO).

Methods: Single-center retrospective case-control study of adults with a history of RVO/RAO. Cases (N = 101) who developed NVG were age and sex matched 1:2 to controls who did not develop NVG (N = 202). Multivariable logistic regression was used to estimate the association between history of PVD and risk of NVG while controlling for other related demographic or clinical factors.

Results: In initial bivariate analyses, there was no difference in risk of NVG based on eye, lens status, hypertension, history of panretinal photocoagulation (PRP), or retinal surgery (all p > 0.10), a borderline difference based on diabetic retinopathy (DR) (p = 0.06) and prior anti-vascular endothelial growth factor (anti-VEGF) treatment (p = 0.08), and a significant difference based on race/ethnicity, type of vascular event, and PVD status (all p < 0.05). In the final multivariable model, patients without PVD were significantly more likely to develop NVG (OR = 3.07, p = 0.0001) independent of the other covariates. Risk of NVG was greater in those with DR (OR = 1.98, p = 0.0440) and in those with central RVO vs. branch RVO/hemiretinal RVO (OR = 5.77, p < 0.0001). Non-White/Non-Hispanics (OR = 2.56, p = 0.0051) and Hispanics (OR = 3.65, p = 0.0288) were more likely than White patients to develop NVG.

Conclusions: Progression to NVG after retinal vascular occlusion is more likely in Non-White/Hispanic patients, those with concomitant DR, and those with CRVO/CRAO. The absence of PVD increases the risk for NVG. Further studies are necessary to understand this relationship.

Topical medical therapy is the most common approach to the treatment of many ocular conditions. While effective, topical therapy has numerous important limitations. Eye drops can have unpleasant or even dangerous side effects, are often difficult to self-administer, and the application of multiple drops per day, possibly from multiple different bottles, can be burdensome. Perhaps the most important limitation of topical medical therapy is non-adherence, a complex multifactorial behavior that increases the risk of poor outcomes associated with undertreatment. There is growing interest in a class of therapeutics termed "procedural pharmaceuticals" (PPs), which remove the responsibility of self-dosing from patients. An array of PPs are available for the treatment of a variety of ocular conditions, such as those for glaucoma, retina, and cataract surgery; and many more will emerge in coming years. A paradigm shift away from patient-administered therapy toward provider-administered therapy will have important implications for both providers and patients. This paper explores the impact that PPs have had, and will have, on the clinical practice of ophthalmology.

Introduction: Our aim was to evaluate the visual and refractive outcomes of iris-fixated phakic toric intraocular lenses (IOLs) for visual rehabilitation in eyes with stable corneal ectasia.

Methods: We conducted a study looking at the clinical outcomes of iris-fixated toric IOLs (Artisan) in 33 eyes of 27 patients diagnosed with mild-to-moderate corneal ectasia at a single center (Queen Victoria Hospital, East Grinstead, UK). The main outcome measures were functional improvement [accuracy of post-operative spherical equivalent (SE), astigmatic correction, topographic parameters, uncorrected and corrected distance visual acuity (UCVA, CDVA)] and safety of the procedure: endothelial cell count and intra- and post-operative complications.

Results: Eighteen males and nine females of mean age 38.85 were included in the study with a mean follow-up of 18 months. All patients had ectasia due to keratoconus except one with post-refractive laser ectasia. Twelve patients had crosslinking, eight had intracorneal rings, and eight had previous keratoplasties. Mean pre-operative logMAR UCVA was 0.75 ± 0.35 improving to 0.02 ± 0.17 (p = 0.000). Mean pre-operative logMAR CDVA was 0.16 ± 0.17 improving to 0.02 ± 0.17 (p = 0.000). Mean pre-operative (SE) was - 3.5 ± 3.9 improving to - 2.75 ± 1.39 (p = 0.000) with up to 36-42 months of follow-up. The mean value of endothelial cell density in the overall sample was 2252.54 ± 473.24 cells/mm² pre-operatively and 2126.75 ± 365.21 cells/mm² at 24-36 months of follow-up visit. Two patients have intra-operative hyphemia secondary to iris prolapse.

Conclusions: Implantation of iris-fixated phakic toric IOLs has shown high efficacy and safety in patients with mild-to-moderate astigmatism in corneal ectasia.

Introduction: The aim of this prospective and comparative study was to investigate the association of perimetry parameters on visual acuity and contrast sensitivity in primary open-angle glaucoma (POAG) eyes with diffractive extended depth-of-focus (EDoF) and monofocal intraocular lenses (IOLs).

Methods: In cataract eyes with medicinally controlled POAG with no defects in the central visual field and mean deviation (MD) values of - 10 dB or better, EDoF and monofocal IOLs with the same platform except for echelette optics for EDoF were implanted in 22 and 24 eyes, respectively. Corrected distance visual acuity (CDVA), contrast sensitivity at 3 to 18 cycles per degree (cpd), and automated perimetry using 30-2 and 10-2 Swedish Interactive Threshold Algorithm programs were examined 3 months postoperatively. The influences of perimetry parameters including MD, foveal sensitivity (FS), and the means of the central four points (central MD and central FS) on CDVA and contrast sensitivity were evaluated using linear and multiple regression analyses.

Results: In POAG eyes with EDoF IOLs, contrast sensitivities at 12 and 18 cpd were associated with 30-2 and 10-2 perimetry parameters. In POAG eyes with monofocal IOLs, associations of 30-2 parameters were found in CDVA and 3-cpd contrast sensitivity.

Conclusions: The visual function of POAG eyes with EDoF IOLs was associated with perimetry parameters in high spatial frequency contrast sensitivity, which was different from that of POAG eyes with monofocal IOL.

Trial registration: Japan Registry for Clinical Research: jRCTs032200218.

Introduction: Despite an improved understanding of its pathogenesis, dry eye disease (DED) remains relatively underestimated and its treatment challenging. A better alignment between the clinical evaluation and the patient self-assessment also requires capturing the whole patient experience of DED. This project aimed to unveil this experience through narrative medicine (NM).

Methods: The project involved 38 expert centres in Italy and one in San Marino, targeting adult patients with DED, their informal caregivers and their treating ophthalmologists. Written narratives and sociodemographic and quality of life (QoL)-related data were anonymously collected through the project's webpage. Narratives were analysed through MAXQDA (VERBI Software, Berlin, Germany), NM classifications and content analysis.

Results: A total of 171 patients with DED, 37 informal caregivers and 81 ophthalmologists participated in the research. DED was defined as a disabling condition by 19% of patients and 35% of caregivers; 70% of patients reported that a therapeutic alliance is an integral part of DED treatment and 32% hope for more effective therapies. Forty-four per cent of patients assessed their own QoL as good; however, DED emerged as importantly impacting work performance and social events. DED physical, emotional and economic burden and the cruciality of a trusting care relationship represent the main themes that emerged across all narratives, while empathy and effective treatment are among the factors favouring coping with DED.

Conclusion: This project marked a pioneering initiative investigating the lived experience of patients with DED through NM, simultaneously involving all viewpoints involved in the care pathway. NM enabled the unveiling of factors favouring the ability to cope with DED and its associated QoL implications and provided valuable insights to improve the therapeutic alliance.

Introduction: High-tech devices for the assessment of dry eye disease (DED) are increasingly available. However, the agreement between high- and low-tech parameters has been poorly explored to date. Trying to fill these gaps, we conducted a post hoc analysis on a recently published retrospective study on patients with DED receiving both low- and high-tech (Keratograph^®) assessments, and treatment with different lubricating eyedrops.

Methods: Six clinical questions were defined by the authors, considering literature gaps and their clinical experience, namely: (1) are NIKBUT-i and T-BUT interchangeable parameters? (2) What was the correlation between low- and high-tech parameters in untreated and treated patients with DED? (3) What was the correlation between signs and symptoms at baseline and during/after treatment? (4) Which parameters were better associated with symptoms? And with symptoms change over time? (5) What was the performance of NIKBUT-i and T-BUT in detecting clinically relevant changes? (6) What was the clinical advantage of adding other high- and low-tech parameters, respectively, to NIKBUT-i and T-BUT?

Results: Low-tech measures were the best descriptors of the Ocular Surface Disease Index (OSDI) at baseline. In contrast, high-tech assessments demonstrate better performance in detecting changes over time. The distribution of NIKBUT-i data was more dispersed than TBUT both at baseline and follow-up. At a fixed specificity of 80%, the sensitivity in detecting clinically relevant ameliorations of symptoms was 42% for NIKBUT-i and 25% for T-BUT. A battery of high-tech tests could detect 90% of clinical amelioration, compared with 45% with low-tech tests (p < 0.001). Correlation between low- and high-tech parameters in both treated and untreated patients is lacking.

Conclusions: Low-tech measures are adequate for diagnostic purposes in DED, whereas high-tech showed better performances at follow-up, particularly when different tests are combined. Overall, poor interchangeability among parameters and agreement with symptoms was reported both with high- and low-tech assessments.