Interval Extension Research Articles

Predicting long-term functional anti-VEGF treatment outcomes in neovascular AMD in a real-world setting.

To test to what degree retinal fluid (RF) after the loading phase and at the end of year 1 predicts long-term functional outcomes in neovascular macular degeneration (nAMD), as do macular (MA) atrophy, treatment density and treatment interval extension. In this retrospective single-center cohort study, a consecutive series of eyes with treatment-naïve nAMD followed under a treat-and-extend (T&E) protocol followed over ≥2 years. Best-corrected visual acuity (BCVA), presence of retinal fluid (RF) and macular atrophy (MA) were registered along with central retinal thickness (CRT) and treatment density over time. The relationship between these variables was tested by regression analysis. A total of 433 eyes were followed for 4.9 ± 2.2 years. A series of univariate analyses were run to select the covariates for the final multivariate regression model. CRT after loading, time to dryness, intraretinal fluid and MA after one year were found to predict visual function over 2 to 5 years. A final regression model was adjusted for visual acuity (VA) at baseline and showed that CRT after loading was predictive only in the short term (2 years) and that MA had the greatest predictive value for VA after 2 to 5 years. Intraretinal fluid (IRF) significantly predicted VA only after 4 years. The final regression model explained 21 to 32% of the variation in VA. In this large retrospective cohort, the presence of MA after one year was the strongest predictor of VA after 2 to 5 years, explaining a vision loss of 13 to 20 letters. The presence of IRF and SRF at any point of time had a comparably weak predictive potential for the outcomes over 5 and more years.

Precision Dosing of Intravenous Tocilizumab: Development of Pharmacokinetic Model-Derived Tapering Strategies for Patients With Rheumatoid Arthritis.

Tocilizumab targets the interleukin-6 receptor, and dosing is complex owing to its nonlinear clearance related to target binding. Therefore, tapering tocilizumab requires a different approach than that of tumor necrosis factor inhibitors (TNFi). This study aimed to identify these differences and enable personalized treatment of rheumatoid arthritis (RA) beyond TNFi therapy. A population pharmacokinetic model of intravenous tocilizumab was developed using data from a randomized controlled trial of dose tapering in patients with RA. Subsequent population-level Monte Carlo and individual Bayesian simulations were performed to create tapering strategies involving dose reduction and interval extension. The target trough concentration of tocilizumab was 5 mg/L. Finally, the drug savings were compared between the 2 methods. The pharmacokinetic of tocilizumab was described with a 2-compartment model with parallel linear (CL 0.20 L/d) and nonlinear (VM 5.2 mg/d, KM 0.19 mg/L) elimination. The linear clearance rate and central volume of distribution increased with lean body mass, and men exhibited higher clearance rates than women. The simulated concentration-time profiles demonstrated that, owing to nonlinear clearance, drug concentrations decreased more than dose-proportionally with lower doses. Tapering based on an individual Bayesian approach emerged as the most promising strategy, yielding a 39% reduction in drug use across virtual populations. Tapering strategies were developed for intravenous tocilizumab, offering potential application in patients with RA who have reached low disease activity or remission, pending clinical validation. The developed strategies demonstrate that the tapering of tocilizumab should be approached more carefully and in smaller steps than that of TNFi.

Real world efficacy and durability of faricimab in patients with neovascular AMD (nAMD) who had sub-optimal response to prior anti-VEGF therapy.

Age-related macular degeneration (AMD) remains a primary cause of blindness, with neovascular AMD (nAMD) presenting particular treatment challenges. Despite anti-vascular endothelial growth factor (anti-VEGF) therapies, many patients exhibit a suboptimal response to the previously available anti-vascular endothelial growth factor (anti-VEGF) therapies. This study evaluates the efficacy and treatment interval extension of faricimab in this patient cohort. In a retrospective single-centre study at University Hospitals of Bristol and Weston, UK, nAMD patients suboptimally responsive to previous anti-VEGF therapies were switched to faricimab. Treatment started with an initiation phase of 4 monthly injections followed by a 'Treat and Extend' protocol. Outcomes included best-recorded visual acuity (BRVA), central subfield thickness (CST), the presence of retinal fluid, and treatment intervals. Among 98 eyes of 79 patients, following faricimab treatment, significant reductions in CST and retinal fluid were noted, indicating decreased disease activity. While BRVA changes were not statistically significant, the anatomical improvements suggest a potential therapeutic benefit. Notably, 40% of patients achieved extended treatment intervals, reducing the treatment burden. Faricimab offers a promising alternative for nAMD patients with suboptimal responses to prior anti-VEGF treatments, demonstrating significant anatomical improvements and the possibility of extended dosing intervals. These findings highlight the need for prospective real-world studies to further assess faricimab's role in nAMD management and its long-term impact on patient outcomes.

Transfer of pesticides and metabolites in corn: Production, processing, and livestock dietary burden

Corn stover is widely used in livestock feed but has received limited attention regarding its potential risks. In this study, pesticide residues were monitored across 12 provinces in China, and terminal residues of four pesticides, chlorantraniliprole, thiamethoxam, epoxiconazole, and pyraclostrobin, were tested. In addition, the silage processing experiment was conducted. All processing factors (PF) were <1, indicating pesticide degradation. The physicochemical properties of pesticides, especially log P, were related to degradation efficiency. Pesticides with higher log P values showed higher PFs (0.43 to 0.85), indicating lower degradation efficiency. The dietary burden of livestock before and after silage processing was calculated using OECD livestock dietary burden calculator. Results showed that after silage fermentation, the dietary burden was reduced by 28.8 % to 79.2 %. Throughout the entire production and processing process, the fastest degradation of all pesticides in whole corn was primarily observed from the pesticide application time to the harvest time, with some pesticides also showing accelerated degradation during subsequent processing stages. Therefore, in actual production, especially for pesticides which are difficult to degrade, appropriate extension of the safety interval or selection of suitable processing methods can be taken to further reduce pesticide residues in agricultural products.

Analysis of the tooth-root stress of external spur gears with high effective contact ratio

For spur gears with contact ratio close to 2, the extension of the contact interval resulting from loaded tooth deflections and local contact deformations may result in an effective contact ratio above 2. In these cases, the load is transmitted by at least two tooth-pairs, the maximum load and tooth-root stress decrease, and therefore the calculation methods of the gear rating Standards ISO and AGMA provide very conservative results. In this work, two models are applied to the calculation of the tooth-root stress of load-induced high contact ratio external gears: (i) an analytic model of load sharing, based on the minimum energy method, and (ii) a finite element model, which validates the results obtained from the previous model. Obtained values of the stress are compared with those provided by ISO and AGMA rating methods, which do not account for the stress reduction due to the higher contact ratio. A new modification coefficient is proposed to correct these conservative values, which allows the AGMA and ISO geometry factors to remain as no load-dependent factors and keep their actual calculation methods and significance.

Treatment regimens for optimising outcomes in patients with neovascular age-related macular degeneration.

Practice patterns for neovascular age-related macular degeneration (nAMD) have evolved from the landmark registration trials of vascular endothelial growth factor (VEGF) inhibitors. Non-monthly regimens like treat-and-extend (T&E) have become popular due to their effectiveness in clinical practice. T&E regimens attempt to limit the burden of visits and treatments by allowing progressively longer treatment intervals, but in so doing, are potentially associated with the expense of treating quiescent disease. This is acceptable to many patients and their ophthalmologists but can still be problematic in the real-world. Recent studies have further refined the T&E approach by allowing for quicker and longer extension of treatment intervals when less severe disease is detected. With newer drugs offering increased durability, a shift to longer regular intervals may emerge as a new practice pattern for VEGF inhibitor therapy. This review aims to consolidate the current literature on the most effective treatment patterns and update treatment guidelines based on options that are now available. It also summarises new aspects of nAMD management that may help to further refine current practice.

Impact of treat and extend criteria on proportions that can be extended after loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration: PRECISE Report 5.

To study the impact of definitions of various treatment extension criteria on the proportion of patients who could be extended at their first visit after the loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration (nAMD). Patients with nAMD initiated on the loading phase of three intravitreal doses of 2 mg aflibercept in routine clinical practice were recruited from December 2019 to August 2021. The response to the loading phase was assessed at approximately 8 weeks post-loading (up to 140 days from first injection) based on different definitions of response. The proportion of patients that qualify for interval extension based on different clinical trial criteria was also evaluated. A total of 722 patients with visual acuity (VA) and optical coherence tomography (OCT) scans done at all 4 visits were included. Of these 32.4% of eyes responded with complete macular fluid resolution after the first injection with no recurrence through the loading phase (super-responders) while 26.9% had persistent macular fluid in all 4 visits (true non-responders). The rest were considered suboptimal responders. Change in VA showed marked variations within each of these categories of fluid resolution. For extension of next treatment interval, if presence of any macular fluid at the post-loading visit is the only criteria considered, about 50% could be extended to 8 weeks. If both VA worsening by ≥5 letters and a > 25 μm increase in central sub-field thickness (CST)are considered, 90% will be eligible for interval extension. Clinical trial designs and pre-defined treatment extension/shortening criteria determine the proportion of patients requiring treatment in the post-loading visit. The short and long-term impact of interval extension immediate post-loading on visual outcome in clinical practice is unknown.

Baseline characteristics associated with the first year treatment interval of intravitreal faricimab in neovascular age-related macular degeneration (nAMD)

AimsTo identify baseline characteristics that best correlate to treatment interval for naive neovascular age-related macular degeneration patients treated with faricimab in the first year (Y1) of the TENAYA and LUCERNE...

Stochastic analysis of combined primary-secondary structures subjected to imprecise seismic excitation

The imprecise stochastic process model is able to incorporate both random and epistemic uncertainties, leading to a more accurate description of environmental excitations, such as earthquakes or wind loads, when limited data are available. Epistemic uncertainties in the loading model may significantly affect the performance of structural systems.The present paper addresses the stochastic analysis of combined primary-secondary structures subjected to imprecise seismic excitation modeled as a zero-mean stationary Gaussian random process, characterized by an interval-valued Power Spectral Density (PSD) function. The power and energy content of the imprecise ground motion acceleration may vary, even for the same soil category, affecting the complex dynamic behavior of combined structures and the vibration control capacity of secondary substructures under different frequency tuning conditions. The main purpose of this study is to develop a framework for investigating both the influence of epistemic uncertainties in the loading model and the interaction effects between the subsystems on the seismic performance of combined primary-secondary structures. To this aim, the stochastic analysis of combined structures under imprecise ground motion acceleration is addressed in both the frequency and time domains by an efficient approach capable of decoupling the propagation of interval and random uncertainties. Seismic safety assessment is performed in the framework of the first-passage theory by interval extension.

Real-World Efficacy of Intravitreal Faricimab for Diabetic Macular Edema: A Systematic Review.

Diabetic macular edema (DME) is a prevalent exudative maculopathy, and anti-vascular endothelial growth factor (anti-VEGF) therapy is the first-line choice for treatment. Faricimab, a novel anti-VEGF and anti-angiopoietin-2 bispecific agent, has recently been approved for the treatment of DME. In this study, we systematically reviewed the real-world evidence of the efficacy of faricimab for the treatment of DME. We searched 11 databases for eligible studies. Study selection and data extraction were made independently by two authors in duplicate. Eligible studies were reviewed qualitatively. We identified 10 eligible studies that summarized data from a total of 6054 eyes with a mean follow-up of between 55 days and 12 months. Five studies reported outcomes in a population of both treatment-naïve and previously treated eyes, and five studies reported outcomes exclusively in relation to eyes that were previously treated. Faricimab improved the best-corrected visual acuity and macular thickness. The extension of the treatment interval was possible in 61-81% of treatment-naïve eyes and 36-78% of previously treated eyes. Faricimab for DME yields clinical outcomes similar to those known from previous anti-VEGF treatments but with extended treatment intervals, thus lowering the burden of therapy for patients. Long-term real-world studies are warranted.

Reducing plastic waste in intensive care from longer use of intravenous administration and invasive monitoring sets: A before-and-after study

IntroductionIntensive care unit (ICU) treatment carries a large environmental burden. Extending routine replacement of plastic line sets that belong to intravenous administration or invasive monitoring might lower waste from single-use plastics in ICUs. We extended the routine replacement interval of line sets from 4 to 7 days and assessed plastic waste reduction. MethodsIn this single center retrospective study the extension of the time interval from 4 to 7 days for routine replacement of line sets and its effect on plastic waste was assessed. The intervention was done at the start of 2022. Secondary outcomes were catheter-related bloodstream infections (CRBSI), nursing workload, costs and material durability. ResultsIn total 1221 patients were admitted to ICU; 636 in the pre-intervention period and 585 in the post-intervention period. There was a reduction of 881 replacement sets, 182 kg of waste and 96 nursing hours in 2022. There was no difference in CRBSI incidence. ConclusionThis study demonstrates the benefits of 7-day replacement intervals for intravenous administration and invasive monitoring sets. We established this in terms of waste reduction, patient safety and costs.

Parametric influence and optimization of the dehumidification performance of a variable-frequency dehumidifier

This paper optimizes a variable-frequency dehumidification system (VFDS) based on the principle of vapor compression refrigeration (VCR), wherein the compressor frequency and fan speed can be changed. The effect of the compressor frequency and fan speed on the operating parameters of the VFDS, including the evaporating temperature (T e), condensing temperature (T c), superheating (ΔT sh), and subcooling (ΔT sc), is studied experimentally under three operating conditions. The effect of variable-frequency on the dehumidification performance is analyzed at the mechanistic level through two dehumidification performance indicators, namely, the dehumidification capacity (DC) and dehumidification energy efficiency (DEE). ΔT sh is primarily controlled by the capillary throttling effect, which always starts to cross the “0” point when the fan speed is 600 rpm under different conditions. An increase in the compressor frequency leads to the opposite trend for DC and DEE, but their corresponding optimal fan speeds are relatively close. At 27 °C/60%, the optimal fan speed intervals with DC and DEE as single optimization objectives are both [600 rpm, 700 rpm]. However, at 30 °C/80%, the overall difference between the optimal fan speed intervals with DC and DEE as optimization objectives is 50–100 rpm. Importantly, the risk of frost at 18.3 °C/60% can lead to a significant extension of the optimal fan speed interval, which is [500 rpm, 900 rpm], making it more difficult to control. The concept of the dehumidification operating temperature difference (ΔT) is proposed to comprehensively evaluate the dehumidification capacity and as a control index for variable frequencies. The relationships among the optimal ΔT and the ambient dew point temperature (Td ) and compressor frequency are established through response surface methodology (RSM) with a maximum deviation of 5.97%. This work can provide an optimized variable-frequency solution for the VFDS and some guidance for the control logic development of the VFDS.

Impact of COVID-19 on a real-world treat-and-extend regimen with aflibercept for neovascular age-related macular degeneration

ObjectiveTo assess the effect of the COVID-19 pandemic on injection intervals among patients treated for neovascular age-related macular degeneration. DesignRetrospective cohort study. ParticipantsPatients treated at a single practice using a treat-and-extend regimen with intravitreal aflibercept between December 2018 and April 2021. MethodsThe primary outcome was the change in injection intervals. Secondary outcomes included differences in best-recorded visual acuity (BRVA) and central subfield thickness (CST). Associations were evaluated with linear mixed-effects modelling. ResultsThis study included 1839 injections from 185 eyes (141 patients). The median (interquartile range) injection intervals in the pre-COVID-19 and COVID-19 periods were 60 (42–70) and 70 (49–90) days, respectively. The pandemic was associated with a mean injection interval lengthening of 7.2 days (P < 0.001), a decrease in BRVA of 3.1 Early Treatment Diabetic Retinopathy Study letters (P < 0.001), and a reduction in CST of 14.7 μm (P = 0.003). The presence of exudative intraretinal fluid was associated with a reduction in treatment intervals of 11.1 days (P < 0.001), a reduction in BRVA of 1.9 Early Treatment Diabetic Retinopathy Study letters (P < 0.001), and an increase in CST of 52.4 μm (P < 0.001). The presence of subretinal fluid was associated with a reduction in treatment intervals of 8.5 days (P < 0.001) and an increase in CST of 21.6 μm (P < 0.001). ConclusionsThis real-world study estimated that the severe acute respiratory syndrome coronavirus 2 pandemic resulted in an injection extension of 7.2 days with associated decreases in BRVA and CST that are unlikely clinically significant on a population basis. This builds on evidence suggesting that long-term vascular endothelial growth factor suppression can facilitate meaningful interval extensions while maintaining visual acuity.

The Clinical Relevance of ECG Parameters in the Prediction of Cardiac Mortality: A Comprehensive Review

About half of all heart disease deaths are caused by cardiac arrest, making it one of the major causes of mortality in prosperous countries. When confronted with potentially fatal arrhythmias, implanted preventive cardioverter defibrillators significantly improve survival chances. However, this is only possible if high-risk patients who are prone to spontaneous cardiac arrest are identified beforehand. The current analysis examines the most recent findings regarding the use of surface electrocardiogram (ECG) data to predict sudden cardiac arrest. Here, we provide a comprehensive overview of the literature on non-invasive ECG techniques for predicting these kinds of cardiovascular crises. Several electrocardiographic risk stratification methods, including T-wave alternans, signal-averaged ECG, T-peak-to-end variation, early repolarization, an extension of the QT interval, QRS duration, QRS cluster patterns, and Holter monitoring, have been reviewed and analysed. These ECG results have shown to be useful as first screening instruments. Nonetheless, no single ECG measure has shown to be an effective technique for classifying individuals based on their risk of sudden cardiac arrest to date. Nevertheless, one or more of these prospective SEM metrics might potentially be important in intricate risk categorization schemes.

Influence of personalized extended interval dosing on the natalizumab wearing-off effect - a sub-study of the NEXT-MS trial

Background and objectivesWearing-off symptoms during natalizumab treatment in multiple sclerosis are characterized by an increase of MS-related symptoms prior to natalizumab administration. The influence of extended interval dosing (EID) on wearing-off symptoms are important to consider, as this might cause hesitancy in initiating or continuing EID. MethodsParticipants of the NEXT-MS trial, in which treatment intervals are adjusted based on drug concentrations, were divided into two groups: an extended group containing participants with at least one week of additional interval extension, and a group with a fixed interval during the trial (range 4–7 weeks). Changes in the occurrence, frequency, onset, and severity of wearing-off symptoms were evaluated. Results255 participants were included (extended group n = 171, fixed group n = 84). The odds on occurrence of wearing-off symptoms in the extended group did not increase after extending the treatment interval. Additional analyses for frequency, onset, and severity of wearing-off symptoms showed no changes over time. Mean decrease in natalizumab drug concentration did not influence the frequency of wearing-off symptoms. DiscussionWearing-off symptoms were not reinforced by further extending the natalizumab interval. Wearing-off symptoms might increase in a minority of patients after EID, although our data support the view that wearing-off symptoms appear to be unrelated to the decrease in natalizumab trough drug concentrations.

Chronic rhinosinusitis with nasal polyps-extension of dupilumab treatment intervals

In patients with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab 300 mg every 2weeks can completely resolve nasal polys, sinus disease, and symptoms. In this case, patients ask for de-escalation. Although trials have demonstrated recurrence after stopping the biologic at 24weeks, reducing the dose of dupilumab to once every 4weeks did not result in deterioration of control. An extension of the treatment intervals would, however, diverge from the approval text, and is currently not recommended. The course of 29patients with severe CRSwNP, type‑2 inflammation-associated comorbidities, and an indication for biologic was retrospectively analyzed. After resolution of CRSwNP and symptoms under biweekly dupilumab 300 mg, the dupilumab interval had been prolonged individually, initially up to 4weeks, thereafter up to 6weeks, if applicable. Control was assessed via quality of life (22-item sinonasal outcome test, SNOT-22), nasal polyp score, and smell identification test (Sniffin' Sticks; Burghart Messtechnik, Holm, Germany). All patients showed an excellent improvement within the first 3months. The dupilumab application interval was extended to 4weeks after 7-31months (median 13months) and to 6weeks (n = 9) after 17-35months (median 23months). No recurrent polyps or symptoms were subsequently observed. In case of maximal regression of polyps and discomfort, extension of dupilumab injection intervals to4 and potentially 6weeks is possible without clinical worsening. Further studies on de-escalation or termination of biologic treatment when CRSwNP control is achieved are essential.

Phytoconstituents of Artemisia Annua as potential inhibitors of SARS CoV2 main protease: an in silico study

BackgroundIn November 2019, the world faced a pandemic called SARS-CoV-2, which became a major threat to humans and continues to be. To overcome this, many plants were explored to find a cure.MethodsTherefore, this research was planned to screen out the active constituents from Artemisia annua that can work against the viral main protease Mpro as this non-structural protein is responsible for the cleavage of replicating enzymes of the virus. Twenty-five biocompounds belonging to different classes namely alpha-pinene, beta-pinene, carvone, myrtenol, quinic acid, caffeic acid, quercetin, rutin, apigenin, chrysoplenetin, arteannunin b, artemisinin, scopoletin, scoparone, artemisinic acid, deoxyartemisnin, artemetin, casticin, sitogluside, beta-sitosterol, dihydroartemisinin, scopolin, artemether, artemotil, artesunate were selected. Virtual screening of these ligands was carried out against drug target Mpro by CB dock.ResultsQuercetin, rutin, casticin, chrysoplenetin, apigenin, artemetin, artesunate, sopolin and sito-gluside were found as hit compounds. Further, ADMET screening was conducted which represented Chrysoplenetin as a lead compound. Azithromycin was used as a standard drug. The interactions were studied by PyMol and visualized in LigPlot. Furthermore, the RMSD graph shows fluctuations at various points at the start of simulation in Top1 (Azithromycin) complex system due to structural changes in the helix-coil-helix and beta-turn-beta changes at specific points resulting in increased RMSD with a time frame of 50 ns. But this change remains stable after the extension of simulation time intervals till 100 ns. On other side, the Top2 complex system remains highly stable throughout the time scale. No such structural dynamics were observed bu the ligand attached to the active site residues binds strongly.ConclusionThis study facilitates researchers to develop and discover more effective and specific therapeutic agents against SARS-CoV-2 and other viral infections. Finally, chrysoplenetin was identified as a more potent drug candidate to act against the viral main protease, which in the future can be helpful.

Extension of interval between adjacent pulse delivery cycles to deal with myocardial ischemia by intravascular lithotripsy: case report

BackgroundIntravascular lithotripsy (IVL) represents a novel approach in the management of coronary calcification. This technique employs acoustic pressure waves, generated by a shockwave balloon, to effectively fracture both superficial and deep calcification in situ. The efficacy and safety of IVL have been convincingly demonstrated through the Disrupt CAD I-IV studies. While IVL is associated with the occurrence of atrial and ventricular arrhythmias, there is no evidence to indicate it causes myocardial ischemia.Case DescriptionA 71-year-old man was admitted presenting with chest pain. His previous coronary angiography revealed stenosis and calcification in the left anterior descending branch. An attempt to predilate the lesion using two Lacrosse non-slip element balloons was unsuccessful. Ventricular premature beats and transient ST-segment depression were captured during the utilization of IVL. The operator gradually extended the pulse emission interval across two consecutive cycles to mitigate myocardial ischemia. Notably, when the interval reached 30s, the patient had no chest pain or ST-segment changes. Subsequent images of intravascular ultrasound confirmed calcification ruptures. Therapeutic intervention included the placement of a stent and the application of a drug-coated balloon in the left anterior descending branch. A telephonic follow-up six months later indicated the patient had no discomfort.ConclusionsThis case underscores the effectiveness of gradually extending the pulse emission interval as a strategic complement to the clinical application of IVL. In certain clinical scenarios, it may become imperative to suspend the pulse delivery to improve myocardial blood supply.

Factors Associated with Success of Switching to Faricimab for Neovascular Age-Related Macular Degeneration Refractory to Intravitreal Aflibercept.

We investigated the factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The primary endpoint was a more than two-week extension of the treatment interval after 6 months. In addition, factors related to the success or failure of extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes from 43 patients. Extended dosing intervals of >2 weeks were identified in 14 eyes (32.6%). A short dosing interval before switching, absence of polypoidal lesions, and thin central choroidal thickness before switching were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend existing dosing intervals.

Anti-VEGF Treatment for Secondary Neovascularization in Pseudoxanthoma Elasticum - Age of Onset, Treatment Frequency, and Visual Outcome

PurposeTo assess the onset, treatment frequency, and visual outcome of anti-vascular endothelial growth factor (anti-VEGF) treatment due to secondary choroidal neovascularization (CNV) in patients with pseudoxanthoma elasticum (PXE). DesignRetrospective cohort study MethodsOne-hundred six eyes of 53 patients with PXE were analyzed. The assessment of CNV activity relied on hemorrhage visible on funduscopy and intra- / subretinal fluid on optical coherence tomography (OCT), individually defining a shortening or extension of treatment interval. Best-corrected visual acuity (BCVA) at baseline, age at anti-VEGF therapy initiation, and BCVA-drop events at exudation onset (worsening of BCVA of 2 or more lines) were documented. Further, we assessed the number of injections during the first year and the total number of injections, the time to treatment initiation of the fellow eye, and BCVA over time. ResultsDuring a median observation period of 77 months (IQR 49; 126) patients received a median number of 28.0 anti VEGF-injections (IQR 9.8; 43.5). Eight patients received no injection (median age at baseline 38.1 years), 11 patients underwent anti-VEGF treatment in one eye (median age 47.2 years) and 34 patients in both eyes (median age 51.8 years). The median age at the first anti-VEGF treatment was 52.80 years (IQR 47.2 – 57.6). Applying Cox regression models, the median 'survival' time of fellow eye until treatment initiation was 16.8 months. In the group of bilateral treated patients, the median time difference was 9.6 months (IQR 2.1 – 32.4, range 0 – 122) The median number of injections was 5.5 per eye in the first year of treatment (IQR 3 – 7) and was associated with the total number of injections in the observation period (2.33, CI 1.22 – 3.44, p<0.001). A better BCVA at the last follow-up visit was associated with a better baseline BCVA (p<0.001, R2=0.318) and with the absence of a BCVA drop at the onset of exudation (p=0.035, R2=0.339). ConclusionsThe results of this study indicate that anti-VEGF treatment is required for most PXE patients at a relatively young age. Once treatment in one eye is initiated, the time to fellow eye treatment is relatively short. A BCVA drop before treatment initiation is a risk factor for worse visual outcomes, suggesting that treatment is prudent before exudation affects the central retina. Given the young age of onset and intensive treatment needs, patients with PXE might particularly benefit from longer-acting anti-VEGF therapeutics.