Association of Keratin 8 Level in Aqueous Humor With Outcomes of Intravitreal Ranibizumab Treatment for Neovascular Age-Related Macular Degeneration.
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ABSTRACT: Purpose
To investigate keratin 8 (KRT8) level in the aqueous humor (AH) of patients with neovascular age-related macular degeneration (nAMD) and elucidate its association with intravitreal ranibizumab (IVR) treatment outcomes.Methods
This prospective study involved 58 eyes of treatment-naïve nAMD patients treated with three IVR doses monthly and whose AH samples were collected at baseline and two months after the initial treatment. KRT8 level was determined using the enzyme-linked immunosorbent assay and compared with that of the control group, which comprised patients who underwent cataract surgery during the same period. The nAMD-affected eyes were classified into responder (dry) and poor responder (persistent fluid) groups, according to optical coherence tomography (OCT) findings at month three. Additionally, associations between the KRT8 level and IVR treatment outcomes were analyzed.Results
The baseline KRT8 level was significantly higher in the AMD group than in the control group. In the AMD group, responders demonstrated significant differences between the KRT8 level at the baseline and month two, whereas poor responders exhibited no significant change. Regression analysis revealed that a higher KRT8 level at month two was significantly associated with persistent fluid upon OCT at months three and six.Conclusions
Monitoring aqueous KRT8 level may facilitate early determination of the therapeutic effects of IVR in nAMD patients and reflect the conditions of retinal pigment epithelium during the disease course.Translational relevance
Monitoring aqueous KRT8 may aid early determination of therapeutic effects of IVR in neovascular AMD patients and reflect the health conditions of retinal pigment epithelium.
SUBMITTER: Shin JY
PROVIDER: S-EPMC8764207 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Purpose. To assess whether intravitreal aflibercept (2.0?mg) can effectively reduce persistent macular exudate and enhance visual acuity in ranibizumab (0.5?mg) and/or bevacizumab (1.25?mg) treatment resistant patients with neovascular age-related macular degeneration. Methods. This retrospective study included 47 treatment resistant eyes from 47 patients switched to intravitreal aflibercept injections after receiving a minimum of 3 injections with either ranibizumab or bevacizumab. Snellen visual acuity and optical coherence tomography were assessed just prior to the first injection (baseline) and prior to the fourth injection (final). Additionally, anatomical regions of persistent macular exudate were tracked to determine if these areas yielded varying responses to aflibercept. Results. At baseline, patients had received an average of 11.3 injections with any prior anti-VEGF drug (SD 5.96). For whole group analysis, baseline and final central retinal thickness were 370.57?µm and 295.7?µm (P ? .001), respectively. Baseline and final retinal fluid volumes were 4.81?mm(3) and 4.37?mm(3) (P ? .001), respectively. Baseline and final logMAR were 0.56 and 0.53 (P = 0.301), respectively. Anatomic location of persistent exudate did not appreciably alter treatment outcome. Conclusion. Central retinal thickness and total retinal fluid volume were reduced in ranibizumab and/or bevacizumab treatment resistant patients following three aflibercept injections. No appreciable change in visual acuity was noted.
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Project description:A remarkable proportion of neovascular age-related macular degeneration (nAMD) patients respond rather poorly to ranibizumab treatment, in spite of the minimum 4-week follow-up and treatment interval. Usually, retreatments are based on nAMD activity as evaluated by Spectral-domain Optical coherence Tomography (SD-OCT), biomicroscopic fundus examination and visual acuity changes. In this prospective pilot study, we aimed to study SD-OCT changes in a high-frequent follow-up manner (weekly (month 0-6), biweekly (month 7-12)) throughout the first year, which consequently led to intravitreal ranibizumab being administered up to biweekly. Best corrected visual acuity (BCVA) was already significantly improved at week 2. Central retinal thickness (CRT), intraretinal and subretinal fluid (SRF) were significantly improved from week 1 onwards. Half of the patients showed nAMD activity at week 2 or 3 and received the first retreatment earlier than 4 weeks after baseline injection. In total, 46% of retreatments were already applied 2 or 3 weeks after the previous treatment. Greater range of CRT and SRF fluctuation during follow-up was associated with lower final BCVA. Lower baseline BCVA and better SRF improvement at week 2 was associated with greater BCVA improvement. In conclusion, high-frequency SD-OCT follow-up provided a good option for adapting treatment in nAMD individually.
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Project description:IntroductionNeovascular age-related macular degeneration (AMD) is the leading cause of severe, irreversible visual impairment in people over 60 years of age. Neovascular AMD is characterized by abnormal growth of blood vessels under the retina, specifically the macula. These vessels leak blood and fluids, damaging the retina and its photoreceptors, resulting in permanent loss of central vision. Vascular endothelial growth factor-A (VEGF-A) has been shown to play a critical role in the pathogenesis of neovascular AMD. In the US, ranibizumab, a VEGF-A blocker, is approved and indicated for the treatment of patients with neovascular AMD.AimsTo review the clinical evidence for ranibizumab in the treatment of neovascular AMD.Evidence reviewPhase III clinical trial data have established ranibizumab as a safe and well-tolerated treatment for neovascular AMD. Monthly intravitreal injections of ranibizumab result in a statistically significantly greater proportion of patients losing <15 letters of visual acuity (VA) and statistically significant increases in the mean number of letters gained compared with controls. Anatomically, ranibizumab results in stabilization in the mean area of choroidal neovascularization (CNV) and statistically significant reductions in the mean area of leakage compared with controls. Although there is limited economic evidence available, ranibizumab therapy for neovascular AMD appears to deliver a significant degree of value gain in terms of quality of life when compared with other neovascular AMD interventions.Place in therapyClinical evidence establishes ranibizumab as a first-line therapy option for virtually all treatable neovascular AMD patients. Updating neovascular AMD treatment guidelines to reflect the evidence base for ranibizumab as a preferred first-line therapy would be beneficial for physicians in making informed treatment choices and ultimately helping to ensure the best care for patients.
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Project description:PurposeNeovascular age-related macular degeneration (nAMD) shows variable treatment response to intravitreal anti-VEGF. This analysis compared the potential of different artificial intelligence (AI)-based machine learning models using OCT and clinical variables to accurately predict at baseline the best-corrected visual acuity (BCVA) at 9 months in response to ranibizumab in patients with nAMD.DesignRetrospective analysis.ParticipantsBaseline and imaging data from patients with subfoveal choroidal neovascularization secondary to age-related macular dengeration.MethodsBaseline data from 502 study eyes from the HARBOR (NCT00891735) prospective clinical trial (monthly ranibizumab 0.5 and 2.0 mg arms) were pooled; 432 baseline OCT volume scans were included in the analysis. Seven models, based on baseline quantitative OCT features (Least absolute shrinkage and selection operator [Lasso] OCT minimum [min], Lasso OCT 1 standard error [SE]); on quantitative OCT features and clinical variables at baseline (Lasso min, Lasso 1SE, CatBoost, RF [random forest]); or on baseline OCT images only (deep learning [DL] model), were systematically compared with a benchmark linear model of baseline age and BCVA. Quantitative OCT features were derived by a DL segmentation model on the volume images, including retinal layer volumes and thicknesses, and retinal fluid biomarkers, including statistics on fluid volume and distribution.Main outcome measuresPrognostic ability of the models was evaluated using coefficient of determination (R2) and median absolute error (MAE; letters).ResultsIn the first cross-validation split, mean R2 (MAE) of the Lasso min, Lasso 1SE, CatBoost, and RF models was 0.46 (7.87), 0.42 (8.43), 0.45 (7.75), and 0.43 (7.60), respectively. These models ranked higher than or similar to the benchmark model (mean R2, 0.41; mean MAE, 8.20 letters) and better than OCT-only models (mean R2: Lasso OCT min, 0.20; Lasso OCT 1SE, 0.16; DL, 0.34). The Lasso min model was selected for detailed analysis; mean R2 (MAE) of the Lasso min and benchmark models for 1000 repeated cross-validation splits were 0.46 (7.7) and 0.42 (8.0), respectively.ConclusionsMachine learning models based on AI-segmented OCT features and clinical variables at baseline may predict future response to ranibizumab treatment in patients with nAMD. However, further developments will be needed to realize the clinical utility of such AI-based tools.Financial disclosuresProprietary or commercial disclosure may be found after the references.
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