Manifestations of intraocular inflammation over time in patients on brolucizumab for neovascular AMD

Purpose To describe the adverse events associated with brolucizumab, in particular the sequence of intraocular inflammation (IOI), retinal vasculitis (RV), and/or retinal vascular occlusion (RO).Methods This was an unmasked post hoc analysis of the randomized HAWK/HARRIER clinical trials. Patients with neovascular AMD in the brolucizumab arms of the trials were included. IOI-related adverse events reported by study investigators were analyzed to determine early signs and the time course of IOI-related adverse events, using a subgroup of patients with definite/probable IOI cases identified in an independent unmasked post hoc review by an external safety review committee. A limited literature review on MI following anti-VEGF therapy was also conducted.Results Among 50 patients with definite/probable IOI cases identified by the safety review committee, 12 had RV or RO adverse events reported by the investigators. For 6 of 12, IOI (other than RV) was reported before RV or RO. The duration from the first IOI adverse event to the first RV or RO adverse event ranged from 16 to 171 days for 5 patients and was 553 days for 1 patient. Four of the 6 patients received >= 1 brolucizumab injection on or after the date of the first IOI adverse event and before the first RV or RO adverse event.Conclusions IOI may precede RV or RO in some patients treated with brolucizumab.Ophthalmic researc

Retinal Vascular Occlusion after COVID-19 Vaccination : More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study

Background: To investigate whether vaccination against SARS-CoV-2 is associated with the onset of retinal vascular occlusive disease (RVOD). Methods: In this multicentre study, data from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were retrospectively collected during a 2-month index period (1 June–31 July 2021) according to a defined protocol. The relation to any previous vaccination was documented for the consecutive case series. Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case– control study using age- and sex-matched controls from the general population (study participants from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was conducted. Results: Four hundred and twenty-one subjects presenting during the index period (61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO, fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our case–control analysis integrating population-based data from the GHS yielded no evidence of an increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60–1.45, p = 0.75) in connection with a vaccination within a 4-week window. Conclusions: To date, there has been no evidence of any association between SARS-CoV-2 vaccination and a higher RVOD risk

Precision, morphology, and histology of corneal flap cuts using a 200-kHz femtosecond laser.

Laser-assisted in situ keratomileusis (LASIK) requires precise corneal flap cutting. Especially the creation of thin flaps has recently gained importance for thin-flap LASIK. Currently, there is a trend towards faster femtosecond lasers that can produce flaps in a short period of time. We analyzed flaps created with a 200-kHz femtosecond laser concerning their cut precision, morphology, and histology.Femtosecond laser flap cutting was performed on 36 porcine cadaver eyes using the prototype 200-kHz femtosecond laser UltraFlap (WaveLight GmbH, Erlangen, Germany). The eyes were assigned to 3 thickness groups, with a cut depth of 100 µm, 130 µm, or 180 µm, respectively. Additionally, flap diameters were varied, ranging from 8.0 mm to 9.5 mm. Flap thicknesses were determined with a micrometer gauge. Flap diameters were measured with a sliding caliper. Furthermore, flaps were created for histologic examination.There were no complications during flap creation. The mean flap thickness and standard deviation was (in micrometers) 96.33 ± 7.45 (intended thickness: 100), 134.67 ± 4.96 (intended thickness: 130), and 174.59 ± 9.35 (intended thickness: 180), respectively. The flap diameter revealed a mean (in mm) of 8.03 ± 0.15 (intended diameter: 8.0), 8.56 ± 0.10 (intended diameter: 8.5), 9.09 ± 0.10 (intended diameter: 9.0), and 9.54 ± 0.15 (intended diameter: 9.5), respectively. Histologic examination showed very little to almost no changes in the structure of the corneal stroma.Flap creation could be performed easily without any complications. The morphology and accuracy of the cuts were very reliable and precise. Histology showed a smooth cut

Effect of 3 excimer laser ablation frequencies (200 Hz, 500 Hz, 1000 Hz) on the cornea using a 1000 Hz scanning-spot excimer laser.

To evaluate the possible side effects on human and porcine cadaver eyes induced by excimer laser ablation with 3 ablation frequencies.Augenklinik, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany.Central epithelial abrasion was performed on porcine and human donor eyes. Next, the porcine eyes were photoablated (-9.00 diopters) at 1 of 3 frequencies (200 Hz, 500 Hz, or 1000 Hz) using a prototype 1000 Hz excimer laser. The human eyes were ablated at 1000 Hz. The surface of the stroma as well as the structure and ultrastructure of the corneal cells and stroma were examined using light microscopy, transmission electron microscopy, and scanning electron microscopy (SEM). Special attention was given to the detection of potential thermal damage and the evaluation of corneal smoothness.Histopathologic examination showed very low to almost no differences between the 3 repetition rates. In all cases, SEM showed an equally smooth surface.The structural and ultrastructural evaluation of corneas treated with ablation frequencies of 200 Hz, 500 Hz, and 1000 Hz showed no specific side effects associated with the high repetition rates. The ablation quality was comparable in the 3 frequency groups. However, the treatment time was significantly less with a high repetition rate, indicating the clinical potential in refractive surgery of excimer lasers with a repetition rate of 1000 Hz.No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes

Central and peripheral pachymetry measurements according to age using the Pentacam rotating Scheimpflug camera.

PURPOSE: To investigate the mean values and standard deviations as well as the reliability of consecutive examinations of central and peripheral corneal thickness measurements according to age using the Pentacam rotating Scheimpflug camera (Oculus, Inc.). SETTING: Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany. METHODS: Seventy-six healthy volunteers were enrolled in a clinical prospective study. Three consecutive Pentacam measurements of 1 eye per subject were taken. Evaluated were the central corneal thickness (CCT), corneal thickness at 4 peripheral points (3.0 mm superior, inferior, nasal, and temporal), and the thinnest point of the cornea. The volunteers were then assigned to 3 groups to assess the influence of increasing age on the study parameters. RESULTS: The mean age of the subjects was 46.6 years +/- 16.8 (SD). The mean CCT was 539.62 +/- 31.87 microm. Peripherally, the corneal thickness was between 11% and 19% higher than centrally, with the superior cornea being the thickest followed by the nasal, the inferior, and the temporal cornea. The thinnest point was located in the inferotemporal quadrant in 92% of eyes and in the superotemporal quadrant in 8%. There was no correlation between age and corneal thickness. Minor mean standard deviations of consecutive measurements were noted in the corneal center (4.33 microm), increasing significantly toward the periphery (mean 8.31 microm). Increasing age was not associated with decreasing reliability. CONCLUSIONS: Using the Pentacam, it was possible to acquire information about corneal thickness across the entire cornea. No correlation was found between increasing age and change in peripheral or CCT. Good reliability was noted for pachymetry measurements decreasing slightly toward the periphery, which was independent of age