The anti-vascular endothelial growth factor (anti-VEGF) injection interval influences treatment burden and compliance in neovascular age-related macular degeneration (nAMD). This real-world study ...investigates visual acuity (VA), injection-interval extension, central macular thickness (CMT) and safety in nAMD eyes switched to the anti-VEGF agent brolucizumab and followed for up to 18 months.
This retrospective study included patients with nAMD who were switched from other anti-VEGF agents to brolucizumab only. Patient eyes were grouped into three nested cohorts with the overall cohort receiving ≥ 1 brolucizumab injection, the second receiving ≥ 3 brolucizumab injections with a follow-up period of ≥ 12 months and the third cohort receiving ≥ 3 brolucizumab injections with a follow-up period of ≥ 18 months. Study endpoints included changes from baseline at 12 or 18 months in VA, injection intervals, and CMT. Sub-group analyses were conducted using baseline injection interval length or baseline VA as qualifiers.
Overall, 482 eyes received ≥ 1 brolucizumab injection; 174 eyes received ≥ 3 brolucizumab injections with ≥ 12 months of follow-up, and 95 eyes received ≥ 3 brolucizumab injections with ≥ 18 months of follow-up. VA (mean 95% confidence intervals) remained stable relative to baseline after 12 months (- 1.1 - 3.7, 1.6 letters; p = 0.42) and 18 months (0.0 - 3.1, 3.1 letters; p = 0.98) of brolucizumab treatment, respectively, and pre-switch injection intervals or baseline VA had no notable effect. Following the switch to brolucizumab, injection intervals were extended from baseline to month 12 by 26.9 (19.7, 34.0) days (p < 0.0001), and eyes with pre-switch injection intervals < 8 weeks were able to have their injection intervals extended by 23.6 days longer than eyes with pre-switch injection intervals ≥ 8 weeks. At 18 months, injection intervals were extended by 36.3 (25.6, 46.9) days (p < 0.0001) compared to baseline. Following switch to brolucizumab, CMT was reduced at both 12 and 18 months (12 months: - 35.2 (- 51.7, - 18.8) µm, p < 0.0001; 18 months: - 38.9 (- 54.3, - 22.0) µm, p < 0.0001). Intraocular inflammation-related adverse events were reported in 4.6% of brolucizumab-treated eyes.
This real-world study demonstrates that injection intervals may be significantly extended with maintained vision and reduced CMT in nAMD eyes switching to brolucizumab therapy from other anti-VEGFs.
Objective: Retrospective, real-world study to evaluate visual acuity (VA), anti-vascular endothelial growth factor (anti-VEGF) injection intervals, and central macular thickness (CMT) in neovascular ...age-related macular degeneration (nAMD) eyes switched to brolucizumab only or to brolucizumab alternating with another anti-VEGF. Methods: The overall study population comprised eyes that were given greater than or equal to 1 brolucizumab injection between 1 October 2019 and 30 November 2021. The brolucizumab-only (BRO) cohort consisted of prior anti-VEGF-treated eyes treated exclusively with greater than or equal to 3 brolucizumab injections over greater than or equal to 12 or greater than or equal to 18 months; the alternating brolucizumab (ALT) cohort comprised prior anti-VEGF-treated eyes treated with greater than or equal to 2 brolucizumab injections and greater than or equal to 1 other anti-VEGF over greater than or equal to 12 or greater than or equal to 18 months. Results: A total of 482 eyes receivedgreater than or equal to >1 brolucizumab injection during the study period. Mean VA changes from baseline were -1.1 + or - 15.1 letters (BRO cohort; n = 174) and 1.3 + or - 13.0 letters (ALT cohort; n = 47) at Month 12, and 0.0 + or - 13.5 letters (BRO cohort; n = 95) and -7.3 + or - 17.2 letters (ALT cohort; n = 29) at Month 18. Mean changes in injection intervals were +26.9 + or - 48.1 days (BRO cohort) and +11.1 + or - 17.3 days (ALT cohort) at Month 12 and +36.3 + or - 52.3 days (BRO cohort) and +14.0 + or - 19.9 days (ALT cohort) at Month 18. Mean changes in CMT were -35.2 + or - 108.1 pm (BRO cohort) and -31.5 + or - 91.2 ILLUSTRATION OMITTED m (ALT cohort) at Month 12 and -38.9 + or - 75.0 microm (BRO cohort) and -9.0 + or - 59.9 microm (ALT cohort) at Month 18. Intraocular inflammation-related adverse events were recorded in 22/482 (4.6%) eyes. Conclusion: Treatment with either brolucizumab alone or brolucizumab alternating with another anti-VEGF can preserve vision, reduce CMT, and extend anti-VEGF injection intervals in patients with nAMD. Keywords: alternating anti-VEGF treatments, brolucizumab, neovascular age-related macular degeneration, wet age-related macular degeneration, 12-month outcomes, 18-month outcomes
Liver biopsy and hepatic venous pressure gradient (HVPG), the gold standard for assessing advanced fibrosis (AF) and clinically significant portal hypertension (CSPH), are invasive, costly, and ...time-consuming.
We investigated if the combination of fibrosis index based on 4 factors (FIB-4) and liver stiffness measure (LSM) can identify AF and more importantly, CSPH.
Patients with chronic liver disease referred for transjugular liver biopsy were analyzed retrospectively. FIB-4 and LSM were compared with liver histology for diagnosing AF. FIB-4, LSM, and platelet count were compared with HVPG for diagnosing CSPH. Optimal cutoffs for predicting CSPH were determined by grid search. A composite log-odds to predict CSPH was derived from logistic regression using LSM, FIB-4, and gender. Internal bootstrap validation and external validation were performed.
A total of 142 patients were included in the derivation; 42.3% had AF, and 11.3% had CSPH using the current gold standards. The area under the receiver operating characteristic curve (AUROC) for LSM, FIB-4, and their combination to predict AF were 0.7550, 0.7049, and 0.7768, respectively. LSM, FIB-4, and platelet count predicted CSPH with AUROC 0.6818, 0.7532, and 0.7240, respectively. LSM plus FIB-4 showed the best performance in predicting CSPH with AUROC 0.8155. Based on LSM, FIB-4, and gender, a novel model-the Portal Hypertension Assessment Tool (PHAT)-was developed to predict CSPH. PHAT score ≥-2.76 predicted CSPH with sensitivity 94%, specificity 67%, positive predictive value 27%, negative predictive value 99%, and accuracy 70%. In internal and external validation, AUROCs for the model were 0.8293 and 0.7899, respectively.
A model consisting of FIB-4, LSM, and gender can identify CSPH among patients with chronic liver disease.
To determine silicone oil droplet frequency and symptomatic impact in patients injected with Norm-Ject (NJ) and/or Becton Dickinson (BD) intravitreal bevacizumab.
This was a retrospective cohort ...study of 426 patients with prior bevacizumab injection(s). Symptomatic floaters questionnaire responses were compiled and statistical analysis was performed using Fisher's exact t test with 95% CI calculated via the modified Wald method.
Patients who received BD intravitreal bevacizumab showed more droplets (67.2%) than those who received NJ intravitreal bevacizumab (7.8%), and droplets increased with injection quantity. However, the symptomatic patients reporting new floaters were similar (NJ: 39.22%, BD: 39.47%).
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To assess the long-term outcomes of intravitreal bevacizumab (IVB) in the treatment of choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS).
Retrospective, ...comparative case series.
Interventional series of 150 eyes in 140 patients treated for subfoveal or juxtafoveal CNV secondary to POHS from January 2006 to January 2010.
Intravitreal bevacizumab monotherapy or combination IVB and verteporfin photodynamic therapy (IVB/PDT).
Visual acuity (VA) at 12 and 24 months was analyzed. Secondary outcome measures included the number of injections per year and treatment-free intervals.
A total of 117 eyes received IVB monotherapy, and 34 eyes underwent combination IVB/PDT treatment. For all patients, the average pretreatment logarithm of minimum angle of resolution (logMAR) was 0.63 (Snellen equivalent 20/86) with a 12-month logMAR VA of 0.45 (Snellen equivalent 20/56) and a 24-month logMAR VA of 0.44 (Snellen equivalent 20/55). The mean follow-up was 21.1 months with an average of 4.24 IVB injections per year. There was no significant difference in initial VA, VA at 12 months, VA at 24 months, or number of eyes with a 3-line gain between the IVB monotherapy and IVB/PDT groups. Thirty-eight percent (39/104) of eyes gained 3 lines or more, and 81.2% (84/104) of subjects had maintained or improved their starting VA at 1 year. The proportion of subjects maintaining a 3-line gain in VA was relatively preserved at 2 years (29.8%, 17/57) and 3 years (30.3%, 10/32) follow-up. There was no increase in the proportion of subjects losing 3 lines or more over 3 years of follow-up.
There is no significant difference in VA outcomes between IVB monotherapy versus IVB/PDT combination therapy. The use of IVB alone or in combination with PDT results in significant visual stabilization in the majority of patients with CNV secondary to POHS.
To compare 20-, 23-, and 25-gauge pars plana vitrectomy (PPV) for repair of primary pseudophakic rhegmatogenous retinal detachment.
One hundred eyes of 94 pseudophakic patients who underwent primary ...rhegmatogenous retinal detachment repair with 20-, 23-, or 25-gauge transconjunctival PPV without scleral buckling were included. The medical records were retrospectively reviewed and the corresponding demographic information, preoperative ophthalmic diagnoses, surgical management, and postoperative course and treatment were recorded.
Retinal detachment repair was performed by one of four surgeons. All eyes underwent primary vitrectomy using either 20-, 23-, or 25-gauge vitrectomy instruments, a wide-angle viewing system, endolaser photocoagulation, and gas or silicone oil tamponade. Single surgery anatomical success was 25 of 28 eyes (89.3%) for 20-gauge, 24 of 27 eyes (88.9%) for 23-gauge, and 42 of 45 eyes (93.3%) for 25-gauge PPV. There was no statistical difference in single operation success or final visual acuity results between the groups and 100% of patients achieved final reattachment.
Twenty-, 23-, and 25-gauge instruments are equally effective options for primary repair of pseudophakic rhegmatogenous retinal detachment.
αA-crystallin is abundant in the lens of the eye and acts as a molecular chaperone by preventing aggregation of denaturing proteins. We previously found that chemical modification of the guanidino ...group of selected arginine residues by a metabolic α-dicarbonyl compound, methylglyoxal (MGO), makes human αA-crystallin a better chaperone. Here, we examined how the introduction of additional guanidino groups and modification by MGO influence the structure and chaperone function of αA-crystallin. αA-crystallin lysine residues were converted to homoarginine by guanidination with o-methylisourea (OMIU) and then modified with MGO. LC-ESI-mass spectrometry identified homoargpyrimidine and homohydroimidazolone adducts after OMIU and MGO treatment. Treatment with 0.25 M OMIU abolished most of the chaperone function. However, subsequent treatment with 1.0 mM MGO not only restored the chaperone function but increased it by ∼40% and ∼60% beyond that of unmodified αA-crystallin, as measured with citrate synthase and insulin aggregation assays, respectively. OMIU treatment reduced the surface hydrophobicity but after MGO treatment, it was ∼39% higher than control. FRET analysis revealed that αA-crystallin subunit exchange rate was markedly retarded by OMIU modification, but was enhanced after MGO modification. These results indicate a pattern of loss and gain of chaperone function within the same protein that is associated with introduction of guanidino groups and their neutralization. These findings support our hypothesis that positively charged guanidino group on arginine residues keeps the chaperone function of αA-crystallin in check and that a metabolic α-dicarbonyl compound neutralizes this charge to restore and enhance chaperone function.
Chronic hepatitis C virus (HCV) is common in the Department of Corrections (DOC). Telemedicine is an effective way to treat HCV. The goal of this report was to demonstrate high SVR rate in DOC ...patients using telemedicine irrespective of the HCV genotype (GT) and DAAs used. Demographic, clinical and laboratory data were prospectively collected. A total of 870 DOC patients were evaluated and completed HCV therapy June 2015‐December 2019 with SVR data were included. The mean age was 50 years, 90% were male, 63% were Caucasian, the majority (79%) had GT 1, 92% were treatment naive, and 80% had advanced fibrosis (FIB‐4 ≥ 3.25 and/or transient elastography ≥ 9.5 kPa). The overall SVR was 97% and was similar among all DAAs irrespective of age, sex, race, HIV status, fibrosis level, GT, ribavirin use, prior treatment experience or DAA duration. We conclude that HCV treatment in the DOC through telemedicine is achievable and highly effective with overall SVR 97%, irrespective of the underlying GT or DAA regimen used and can eliminate HCV in this microenvironment and reduce the overall burden of HCV.
This study evaluated changes in best corrected visual acuity (BCVA) and submacular hemorrhage (SMH) resolution in eyes after a single rapid subretinal displacement surgery using subretinal Balanced ...Saline Solution (BSS) and sterile air without tissue plasminogen activator (tPA).
A retrospective, comparative, interventional analysis.
Twenty-six eyes with thick SMH who underwent pars plana vitrectomy (PPV) and subretinal fluid displacement without tPA from 2015 and 2021, and at least one-year of follow up.
Surgical intervention included a standard small gauge PPV with subretinal displacement using BSS with subretinal sterile air and partial gas/air fluid exchange. Main outcome measures included degree of subfoveal SMH displacement, best and final postoperative visual acuity (VA), and adverse events. Snellen acuity was converted to LogMAR for statistical analysis.
Most common etiology associated with thick SMH (92.3%) was neovascular age-related macular degeneration (nAMD). Within one-month postoperative, 21 (80.8%) cases saw complete subfoveal blood displacement. Most of SMH surgical displacements were done within a week of presenting symptoms. Average pre-surgical duration of SMH was 3.60 ± 2.78 days (range = 1-12 days). Mean LogMAR BCVA improved from 1.63 ± 0.58 (Snellen 20/800 baseline) to 0.90 ± 0.42 letters (Snellen 20/160) at last follow-up (p=0.001). This study's VA improvement is comparable to prior tPA utilizing studies. Early postoperative complications included one retinal detachment, one vitreous hemorrhage and one macular hole case.
Rapid surgery with subretinal BSS/sterile air injection without tPA was found effective for displacement of thick SMH with retinal function, VA, and CRT improvement.
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