Viscoelastic, Optical, and Surgical Properties of Vitreous Body Replacement Hydrogels After Aging Compared to Porcine Vitreous Bodies And Silicone Oils.

Purpose: First- (monomers), second- (pre-gelated), and third- (in situ gelating after injection) generation hydrogels were previously introduced to replace the vitreous body after vitrectomy surgery. In this study, we evaluated the surgical, optical, and viscoelastic properties of vitreous body replacement hydrogels before and after an accelerated aging protocol previously applied to intraocular implants. Methods: Measurements of injection force, removal speed using a clinically established vitrectomy setup, as well as evaluation of forward light scattering and viscoelastic properties before and after an accelerated aging protocol were conducted. Results were compared to porcine and human vitreous bodies, as well as currently clinically applied lighter- and heavier-than-water silicone oils. Results: Removal speed of all tested hydrogels is substantially lower than the removal speed of porcine vitreous body (0.2 g/min vs. 2.7 g/min for the best performing hydrogel and porcine vitreous body, respectively). Forward light scattering in second-generation vitreous body replacement hydrogels was higher after the aging process than the straylight of the average 70-year-old vitreous body (9.4 vs. 5.5 deg2/sr, respectively). The viscoelastic properties of all hydrogels did not change in a clinically meaningful manner; however, trends toward greater stiffness and greater elasticity after aging were apparent. Conclusions: This study demonstrates surgical weaknesses of the hydrogels that need to be addressed before clinical use, especially low removal speed. Pre-linked hydrogels (second-generation) showed inferior performance regarding surgical properties compared to in situ gelating hydrogels (third-generation). Translational Relevance: This study highlights possible pitfalls regarding surgical and optical properties when applying vitreous replacement hydrogels clinically.

Biomechanical changes following corneal crosslinking in keratoconus patients.

PURPOSE: To evaluate the biomechanical and tomographic outcomes of keratoconus patients up to four years after corneal crosslinking (CXL). METHODS: In this longitudinal retrospective-prospective single-center case series, the preoperative tomographic and biomechanical results from 200 keratoconus eyes of 161 patients undergoing CXL were compared to follow-up examinations at three-months, six-months, one-year, two-years, three-years, and four-years after CXL. Primary outcomes included the Corvis Biomechanical Factor (CBiF) and five biomechanical response parameters obtained from the Corvis ST. Tomographically, the Belin-Ambrósio deviation index (BAD-D) and the maximal keratometry (Kmax) measured by the Pentacam were analyzed. Additionally, Corvis E-staging, the thinnest corneal thickness (TCT), and the best-corrected visual acuity (BCVA) were obtained. Primary outcomes were compared using a paired t-test. RESULTS: The CBiF decreased significantly at the six-month (p < 0.001) and one-year (p < 0.001) follow-ups when compared to preoperative values. E-staging behaved accordingly to the CBiF. Within the two- to four-year follow-ups, the biomechanical outcomes showed no significant differences when compared to preoperative. Tomographically, the BAD-D increased significantly during the first year after CXL with a maximum at six-months (p < 0.001), while Kmax decreased significantly (p < 0.001) and continuously up to four years after CXL. The TCT was lower at all postoperative follow-up visits compared to preoperative, and the BCVA improved. CONCLUSION: In the first year after CXL, there was a temporary progression in both the biomechanical CBiF and E-staging, as well as in the tomographic analysis. CXL contributes to the stabilization of both the tomographic and biomechanical properties of the cornea up to four years postoperatively.

Evaluation of Dry Eye Treatment with Sodium Hyaluronate- and Dexpanthenol-Containing Eye Drops on Ocular Surface Improvement after Cataract Surgery.

BACKGROUND: To clinically evaluate how dry eye symptoms in preoperatively diagnosed dry eye patients change with the use of sodium hyaluronate- and dexpanthenol-containing eye drops (HYLO CARE (HC), URSAPHARM Arzneimittel GmbH, Saarbruecken, Germany) after cataract surgery. The aim of the study was not to compare different eye drops but to implement standard treatment in patients with dry eye undergoing cataract surgery. The impact of treatment was evaluated using Symptom Assessment Tools for Dry Eye. METHODS: In this prospective, single-center, open-label clinical trial, 49 patients undergoing cataract surgery were included who showed signs and symptoms of dry eye disease assessed by the Symptom Assessment in Dry Eye (Visual Analogue Scale (VAS)) questionnaire, Ocular Surface Disease Index (OSDI), and fluorescein tear break-up Time (TBUT). Patients were instructed to apply HC three to four times a day for 5 weeks in the operated eye in addition to the standard postoperative topical anti-inflammatory regimen. The primary endpoint was the change in TBUT. Secondary endpoints were the assessment of the subjective symptoms (VAS), corrected distance visual acuity (CDVA), and slit-lamp examination including the corneal staining score, Schirmer test, and intraocular pressure. RESULTS: At 5 weeks after operation, the mean TBUT increased from 6.42 ± 1.57 s (s) to 7.81 ± 1.83 s in the per-protocol (PP) population (p > 0.001) and from 6.33 ± 1.64 s to 7.71 ± 2.05 s in the intention-to-treat (ITT) population (p < 0.001). There was a statistically significant decrease in all scores (p < 0.05) from the VAS questionnaire except for the tearing score (p = 0.062) at 5 weeks after operation. The mean total corneal staining score also decreased statistically significantly from 8.85 ± 2.49 before operation to 5.61 ± 3.37 at 5 weeks after operation on a 15-point scale. CONCLUSIONS: Controlled standardized dry eye treatment (with HC) improved tear film stability, ocular surface defects, and subjective symptoms of dry eye disease in patients 5 weeks after undergoing cataract surgery. Both the patient and physician assessments indicated high efficacy, tolerability, and a reliable safety profile, as indicated by the low number of at least possibly related adverse events (AE), suggesting its beneficial role in the postoperative management of the ocular surface (OS) in patients with dry eye symptoms prior to and after cataract surgery.

Risk Factors for Corneal Monochromatic Aberrations and Implications for Multifocal and Extended Depth-of-Focus Intraocular Lens Implantation.

PURPOSE: To discuss factors influencing corneal aberrations that might influence the optical quality after intraocular lens (IOL) implantation. METHODS: PubMed and Scopus were the main resources used to search the medical literature. An extensive search was performed to identify relevant articles concerning factors influencing the level of corneal aberrations as of August 27, 2023. The following keywords were used in various combinations: corneal, aberrations, defocus, astigmatism, spherical aberration, coma, trefoil, quadrafoil, intraocular lens, and IOL. RESULTS: Conclusive evidence is lacking regarding the correlation between age and changes in corneal aberrations. Patients with astigmatism have greater corneal higher-order aberrations than those with minimal astigmatism, particularly concerning trefoil and coma. Increased levels of corneal higher-order aberrations are noted following contact lens wear, in patients with dry eye disease, and with pterygium. Increased higher-order aberrations have been reported following corneal refractive surgery and for 3 months following trabeculectomy; regarding intraocular lens surgery, the results remain controversial. CONCLUSIONS: Several factors influence the level of corneal higher-order aberrations. Multifocal and extended depth-of-focus IOLs can share similarities in their optical properties, and the main difference arises in their design and performance with respect to spherical aberration. Preoperative evaluation is critical for proper IOL choice, particularly in corneas with risk of high levels of aberrations. [J Refract Surg. 2024;40(6):e420-e434.].

Early REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION): Study protocol of a phase III trial.

RATIONALE: Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data are lacking to address this question. AIMS: The REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION) investigates intravenous alteplase within 4.5 h of monocular vision loss due to acute CRAO. METHODS: This study is the randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial. STUDY OUTCOMES: Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best-corrected visual acuity of the Logarithm of the Minimum Angle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy outcomes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomography/angiography, ultrasound and magnetic resonance imaging (MRI) biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha = 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm. DISCUSSION: By enrolling patients within 4.5 h of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may translate to CRAO with its similar pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.

Forward Light Scattering of the Vitreous Gel After Enzymatic Aging: An In Vitro Model to Study Vitreous Opacification.

Purpose: Symptomatic vitreous opacifications, so-called floaters, are difficult to objectively assess majorly limiting the possibility of in vitro studies. Forward light scattering was found previously to be increased in eyes with symptomatic floaters. Using an objective setup to measure forward light scattering, we studied the effects of enzymatically digesting the components of the vitreous body on straylight to develop an in vitro model of vitreous opacifications. Methods: Fifty-seven porcine vitreous bodies were digested using hyaluronidase, collagenase, trypsin, and bromelain, as well as using a combination of hyaluronidase + collagenase and hyaluronidase + bromelain. A modified C-Quant setup was used to objectively assess forward light scattering. Results: Depletion of hyaluronic acid majorly increased vitreous straylight (mean increase 34.4 deg2/sr; P = 0.01), whereas primarily digesting the vitreous gel with collagenase or trypsin did not significantly affect straylight. When collagenase or bromelain is applied in hyaluronic acid depleted vitreous gels, the increase in forward light scattering is reversed partially. Conclusions: The age-related loss of hyaluronic acid primarily drives the increase in vitreous gel straylight induced by conglomerates of collagen. This process can be reversed partially by digesting collagen. This in vitro model allows the objective quantification and statistical comparison of straylight burden caused by vitreous opacities and, thus, can serve as a first testing ground for pharmacological therapies, as demonstrated with bromelain.

Ectasia Detection by Anterior Segment Optical Coherence Tomography in Scheimpflug Tomographically Normal Keratoconus Fellow Eyes.

PURPOSE: The purpose of this study was to determine whether the Scheimpflug tomographically normal fellow eyes of keratoconus patients are also classified as normal using an ectasia screening algorithm based on anterior segment optical coherence tomography (AS-OCT). METHODS: This monocentric cross-sectional study included 22 very asymmetric ectasia patients with tomographically significant keratoconus in 1 eye and normal Scheimpflug tomography in the fellow eye. Twenty-two eyes of 22 healthy subjects served as a control group. We performed corneal tomography using Pentacam AXL (Oculus, Wetzlar, Germany) and used Belin/Ambrósio Enhanced Ectasia total deviation index as well as Belin ABCD keratoconus classification to identify Scheimpflug tomographically normal eyes. We also performed AS-OCT using Anterion (Heidelberg Engineering, Heidelberg, Germany) and analyzed for the presence of ectasia using the Screening Corneal Objective Risk of Ectasia (SCORE) algorithm, with positive values indicating ectasia suspect tomography. RESULTS: The SCORE value was positive in 9.1% (n = 2) of the healthy eyes, in 45.5% (n = 10) of the Scheimpflug tomographically normal eyes of keratoconus patients and in all eyes (n = 22) with tomographically significant keratoconus. The Scheimpflug tomographically normal eyes of keratoconus patients had higher SCORE values compared with healthy controls (P < 0.001). The median (interquartile range) SCORE value was -1.7 (1.3) in healthy controls, -0.5 (2.2) in Scheimpflug tomographically normal eyes of keratoconus patients, and 11.1 (11.0) in tomographically significant keratoconus eyes. CONCLUSIONS: The Scheimpflug tomographically normal fellow eyes of keratoconus patients had higher AS-OCT-based SCORE values than healthy controls, with positive SCORE values found in 46% of the eyes, indicating early tomographic ectatic changes.

International Multicenter, Myopic and Myopic Astigmatism Femto LASIK, Customized by Automated Ray-Tracing Ablation Profile Calculation: A Postmarket Study.

Purpose: To assess the safety and efficacy of a customized ablation treatment (InnovEyes) to correct myopia and myopic astigmatism with femtosecond laser-assisted in situ keratomileusis (Femto LASIK). Patients and Methods: In this prospective, nonrandomized, multicenter study, 113 patients (225 eyes) with preoperative myopia less than -9.0 diopters (D) and astigmatism 0 to -4.0 D (based on InnovEyes refraction) underwent wavefront, tomography, and biometry assessment using a single diagnostic device (InnovEyes sightmap). These data were imported and used unmodified by the InnovEyes algorithm to automatically calculate and optimize correction of lower- and higher­order aberrations (HOAs) treated by the EX500 ablation profile. Visual acuity, refractive error, HOAs, and patient satisfaction were evaluated over 3 months. Results: A total of 106 patients (212 eyes) completed the study and were included in the analysis. Mean preoperative manifest refraction spherical equivalent (MRSE) was -3.38±1.76 D. At Month 3, uncorrected distance visual acuity was 20/20 or better in 208/212 (98.1%) eyes, and it was the same as, or better than, the preoperative best-corrected distance visual acuity (CDVA) in 162/212 (76.4%) eyes; 76/212 (35.8%) eyes gained ≥1 line of CDVA. MRSE was within ±0.5 D in 195/212 (92.0%) eyes. Additionally, 201/209 (96.2%) eyes had no change (defined as a change between -0.1 µm and 0.1 µm, inclusive) in HOAs, and 105/106 (99.1%) patients reported to be satisfied with the results. Conclusion: Customizing ray-tracing Femto LASIK with this platform appeared safe and effective in correcting myopic astigmatism and also achieved a significant percentage of eyes gaining lines of vision, potentially by addressing HOAs, along with a consistently high level of patient satisfaction.

Blue-Light Filtering Monofocal Intraocular Lenses: A Study on Optical Function and Tolerance to Misalignment.

PURPOSE: To investigate the optical performance and tolerance to misalignment of blue-light filtering monofocal intraocular lenses (IOLs). METHODS: The optical properties of two monofocal IOLs featuring yellow chromophores, CT Lucia 621 PY (Carl Zeiss Meditec AG) and Clareon CNA0T0 (Alcon Laboratories, Inc), were assessed in monochromatic and polychromatic light while introducing spherical aberration (SA). Optical quality metrics derived from the modulation transfer function were assessed after optimal IOL centration at 3- and 4.5-mm pupils. In addition, each IOL's tolerance to misalignment was examined by inducing up to 1 mm of decentration and the effect of tilting it by 5 degrees at 3 mm. RESULTS: The IOLs' resolution and contrast, while tested using a 3-mm aperture and an SA-neutral corneal model, indicated the CT Lucia 621 PY had a slightly higher modulation transfer function (MTF) at 50 lp/mm than the CNA0T0 under monochromatic conditions (0.77 vs 0.69). On introducing SA with (0.49 vs 0.40) and without (0.75 vs. 0.70) chromatic aberration, the CT Lucia 621 PY maintained its minimally better performance. When assessed with a 4.5-mm aperture in monochromatic light, the CT Lucia 621 PY displayed improved MTF with aberration-free cornea (0.71 vs 0.40) but performed worse after introducing SA (0.44 vs 0.62). However, both lenses achieved comparable MTF values under spherical and chromatic aberrations (0.28 vs 0.27). The IOL misalignment test revealed a better tolerance to tilt and decentration of the CT Lucia 621 PY across all conditions. CONCLUSIONS: The CT Lucia 621 PY and CNA0T0 showed similar optical quality in different situations, with equal simulated distance visual acuity for both models. However, the CT Lucia 621 PY's aspheric design offers an advantage when dealing with often imperfect physiological conditions, displaying a more robust performance under tilt and decentration. [J Refract Surg. 2024;40(2):e79-e88.].

Longitudinal Evaluation of Biomechanical Indices in Fellow Eyes of Patients With Keratoconus Classified as Having Very Asymmetric Ectasia With Normal Topography.

PURPOSE: To evaluate the biomechanical longitudinal variability and progression of tomographically normal fellow eyes of patients with keratoconus. METHODS: Of 513 patients with keratoconus, 30 patients with tomographically normal fellow eyes were included in this study. Tomographic and biomechanical parameters of the Pentacam and Corvis ST (Oculus Optikgeräte GmbH) were analyzed in multiple follow-up examinations, including the ABCD grading, Belin/Ambrósio Enhanced Ectasia total deviation index (BAD-D), Corvis Biomechanical Index (CBI), Corvis Biomechanical Factor (CBiF), and Tomographic and Biomechanical Index (TBI). A mixed regression model was applied. The results were compared to a healthy control group (n = 17) and a keratoconus group (n = 20). RESULTS: Within a maximum observation period of 3.3 years, no fellow eye (0%) showed a progression to tomographically evident keratoconus. No significant change in tomographic or biomechanical parameters was detected over the study period. The indices BAD-D, CBI, CbiF, and TBI exhibited a certain variability over time, whereas the tomographic ABC parameters and maximum keratometry barely changed. This was also shown in the control group and for all parameters in the keratoconus group, except the TBI. CONCLUSIONS: During the observation period none of the normal fellow eyes progressed to tomographically detectable keratoconus. However, biomechanical parameters CBI, CbiF, and TBI showed pathological values in 43.3% of eyes and certain variability. Subsequent studies with a longer observation period are warranted to confirm the biomechanical trends seen in this study and to rate the ability of single measurements to diagnose early keratoconus. [J Refract Surg. 2024;40(1):e48-e56.].