Donor plasma VEGF-A as a biomarker for myocardial injury and primary graft dysfunction after heart transplantation.

BACKGROUND: Vascular endothelial growth factor (VEGF)-A is an angiogenic and proinflammatory cytokine with profound effects on microvascular permeability and vasodilation. Several processes may induce VEGF-A expression in brain-dead organ donors. However, it remains unclear whether donor VEGF-A is linked to adverse outcomes after heart transplantation. METHODS: We examined plasma VEGF-A levels from 83 heart transplant donors as well as the clinical data of these donors and their respective recipients operated between 2010 and 2016. The donor plasma was analyzed using Luminex-based Multiplex and confirmed with a single-target ELISA. Based on donor VEGF-A plasma levels, the recipients were divided into 3 equal-sized groups (low VEGF <500 ng/liter, n = 28; moderate VEGF 500-3000 ng/liter, n = 28; and high VEGF >3000 ng/liter, n = 27). Biochemical and clinical parameters of myocardial injury as well as heart transplant and kidney function were followed-up for one year, while rejection episodes, development of cardiac allograft vasculopathy, and mortality were monitored for 5 years. RESULTS: Baseline parameters were comparable between the donor groups, except for age, where median ages of 40, 45, and 50 were observed for low, moderate, and high donor plasma VEGF levels groups, respectively, and therefore donor age was included as a confounding factor. High donor plasma VEGF-A levels were associated with pronounced myocardial injury (TnT and TnI), a higher inotrope score, and a higher incidence of primary graft dysfunction in the recipient after heart transplantation. Furthermore, recipients with allografts from donors with high plasma VEGF-A levels had a longer length of stay in the intensive care unit and the hospital, and an increased likelihood for prolonged renal replacement therapy. CONCLUSIONS: Our findings suggest that elevated donor plasma VEGF-A levels were associated with adverse outcomes in heart transplant recipients, particularly in terms of myocardial injury, primary graft dysfunction, and long-term renal complications. Donor VEGF-A may serve as a potential biomarker for predicting these adverse outcomes and identifying extended donor criteria.

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.].

The Effect of Blue-light Filtering Intraocular Lenses on the Development and Progression of Macular Atrophy in Eyes With Neovascular Age-related Macular Degeneration.

PURPOSE: To assess the effect of blue-light filtering (BLF) intraocular lenses (IOLs) on the development and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective, clinical cohort study. METHODS: The study included patients with nAMD with anti-vascular endothelial growth factor (VEGF) injections who underwent uneventful cataract surgery between 2007 and 2018 with follow-up until June 2023. Subsequent MA rates were compared between subjects who received a BLF IOL or a non-BLF IOL. All optical coherence tomography scans were manually reviewed in a masked manner regarding patient baseline variables and IOL status by an experienced research technician. By using Heidelberg software, the area of MA was manually evaluated and calculated (mm2) by the program. The overall risk of developing new-onset MA and the effect of IOL type on disease progression were assessed. Death was included as a censoring event. RESULTS: Included were 373 eyes of 373 patients (mean age, 78.6 ± 6.7 years at surgery; 67.4% were female). BLF IOLs were implanted in 206 eyes, and non-BLF IOLs were implanted in 167 eyes with comparable follow-up times (3164 ± 1420 days vs 3180 ± 1403 days, respectively, P = .908) and other baseline parameters (age, gender, corrected distance visual acuity, macular thickness, cumulative number of anti-VEGF injections). Nine preexisting and 77 new-onset MA cases were detected, with similar distribution between BLF and non-BLF eyes (P = .598 and P = .399, respectively). Both univariate Kaplan-Meier (P = .366) and multivariate Cox regression analyses adjusted for age and gender showed that BLF-IOLs were comparable to non-BLF IOLs regarding hazard for new-onset MA (hazard ratio [HR], 1.236; 95% CI, 0.784-1.949; P = .363). Final MA area at the last visit was 5.14 ± 4.71 mm2 for BLF IOLs and 8.56 ± 9.17 mm2 for non-BLF IOLs (P = .028), with the mean annual MA area increase of 0.78 ± 0.84 mm2 and 1.26 ± 1.32 mm2, respectively (P = .042). CONCLUSIONS: BLF IOLs did not show added benefit over non-BLF IOLs in terms of MA-free survival but were associated with less progression over time in a cohort of patients with nAMD.

Choroidal arterial abnormality in central serous chorioretinopathy.

PURPOSE: To evaluate the choroidal arterial abnormality in central serous chorioretinopathy (CSC). METHODS: Fifty-two eyes from 52 patients with CSC were retrospectively evaluated. Arterial and venous ultrawide-field indocyanine green angiography were merged after color and transparency adjustments to compare the choroidal arterial and venous vasculature. Specifically, we evaluated whether the choroidal arteries directly fill the pachyvessel without interconnection of choriocapillaris (arterial pachyvessel; aPV). Then, the clinical characteristics of patients with and without arterial pachyvessel were compared. RESULTS: Pachyvessel under subretinal fluid was detected in 47 of 52 eyes (90.4%). An arterial pachyvessel was detected in eight of 52 eyes (15.4%). Of those eight eyes with arterial pachyvessel, seven (87.5%) showed sustained staining through the venous phase, suggesting they are arteriovenous shunt, while one eye (12.5%) showed diminished fluorescence in the venous phase, suggesting this pachyvessel was purely an artery. Patients with arterial pachyvessel experienced more CSC recurrences (non-aPV group: 2.09 ± 1.44 times vs. aPV group: 3.25 ± 1.28 times; p = 0.039) and pachychoroid neovasculopathy (PNV) development (non-aPV group: 2.3% vs. aPV group: 37.5%, p = 0.009). CONCLUSION: The presence of arterial pachyvessel in eyes with CSC may represent choroidal circulatory imbalance and focal shear stress to Bruch's membrane, leading to a chronic nature and PNV development.

Efficacy comparison of combining cross-linking and refractive laser ablation in progressive keratoconus: systematic review and meta-analysis.

OBJECTIVE: This study assessed the effect of combining corneal collagen cross-linking (CXL) with refractive laser ablation techniques for the treatment of keratoconus, a progressive corneal disorder. METHODS: We performed a systematic review and meta-analysis to assess the effect of combined CXL and refractive techniques. We included all published clinical trials or observational studies published by September 1, 2023. We calculated and compared the standardized mean difference (SMD) between CXL alone and CXL plus laser ablation for uncorrected distance visual acuity, best-corrected distance visual acuity, spherical equivalent manifest refraction, sphere and cylinder, flat keratometry (K1), steep keratometry (K2), and central corneal thickness. RESULTS: We identified 13 studies that fulfilled our inclusion and exclusion criteria. The average follow-up was 21.3 ± 11.8 months. The CXL plus laser ablation group showed improvement in uncorrected distance visual acuity logMAR (SMD, -0.35; 95% CI, -0.67 to -0.04; p = 0.029), best-corrected distance visual acuity logMAR (SMD, -0.17; 95% CI, -0.30 to -0.03; p = 0.014), spherical equivalent manifest refraction (SMD, -0.28; 95% CI, 0.06-0.50; p = 0.013), and change in maximal corneal curvature (Kmax; SMD, -0.41; 95% CI, -0.69 to -0.13; p = 0.004) compared with CXL alone. However, central corneal thickness decreased further among patients who underwent CXL plus laser ablation (SMD, -0.37; 95% CI, -0.66 to -0.07; p = 0.016). No effect was observed in terms of sphere (p = 0.878), cylinder (p = 0.859), K1 (p = 0.907), or K2 (p = 0.169). Ectasia was not observed as an adverse effect resulting from the additional corneal ablation performed during the CXL treatments. CONCLUSIONS: This study showed that combining refractive laser ablation techniques with standard or accelerated CXL treatment improved visual and refractive outcomes and anterior corneal curvature values.

Type 1 and type 2 diabetes predisposed to higher Nd:YAG capsulotomy rates following cataract surgery: analysis of 53,471 consecutive cases.

OBJECTIVE: To assess the effect of diabetes type on Nd:YAG capsulotomy rates following cataract surgery. DESIGN: A retrospective cohort study. METHODS: All patients who underwent cataract extraction at the Department of Ophthalmology, Bristol Eye Hospital, Bristol, UK, between 2003 and 2017 were included. The Nd:YAG capsulotomy rate following cataract surgery was assessed and compared between nondiabetic, type 1 diabetes (T1D), and type 2 diabetes (T2D) patients. Multivariate Cox regression analysis controlling for age and sex was used to estimate hazard ratios for Nd:YAG laser capsulotomies. RESULTS: Included were 53,471 consecutive cataract surgeries. Overall, 42,651 eyes (79.8%) were in nondiabetic patients, 823 eyes (1.5%) were in T1D patients, and 9,997 eyes (18.7%) were in T2D patients. The mean follow-up time was 6.8 ± 4.2 years. In univariate analysis, the eyes of T1D patients (p < 0.001) and T2D patients (p = 0.003) had significantly higher Nd:YAG laser capsulotomy rates than the eyes of nondiabetic patients. In Cox regression analysis adjusted for the patient's age and sex, DM1 (HR 1.692, 95%CI 1.390-2.059, P<0.001) and DM2 (HR 1.157, 95%CI 1.075-1.244, P<0.001) remained significantly predictive for higher Nd:YAG laser capsulotomy rates. CONCLUSION: In our large cohort study, patients with T1D and T2D were predisposed to high risk for Nd:YAG capsulotomy following cataract surgery. This study may be beneficial and raise awareness regarding the assessment of posterior capsular opacification development in pseudophakic diabetic patients, particularly those with T1D. The significance of ophthalmology screening for diabetes individuals is further supported by this issue.

Gestational Diabetes Mellitus, Obstetric Data, and Simple Congenital Ptosis.

PURPOSE: This retrospective cohort study aimed to identify obstetric risk factors for simple congenital ptosis and propose an underlying pathophysiological mechanism. METHODS: Newborns diagnosed with simple congenital ptosis (n = 51) were compared with existing population data in terms of obstetric parameters. RESULTS: Positive associations were found between simple congenital ptosis and gestational diabetes mellitus (11.8% vs. 5%, p = 0.026), preterm delivery (15.7% vs. 0.05%, p < 0.001), and lower birth weight (2,998 ± 506 vs. 3,255 ± 484, p < 0.001). CONCLUSIONS: This study pioneers an association between simple congenital ptosis and gestational diabetes mellitus, potentially linked to insulin-like growth factor 1 levels. We advocate for early ophthalmology checkups for specific newborn subsets.

Ultra-Widefield-Guided Swept-Source OCT Findings of Peripheral Vitreoretinal Abnormality in Young Myopes.

PURPOSE: To evaluate the ultra-widefield fundus photography (UWF-FP)-guided swept-source OCT (SS-OCT) images of peripheral vitreoretinal abnormality (PVRA) in young asymptomatic myopes. DESIGN: Cross-sectional, single-center study. PARTICIPANTS: A total of 1966 eyes of 983 consecutive patients aged 18 to 42 years with refractive error in the spherical equivalent of < 0 diopters (D) who visited KEYE Eye Center, Seoul, Republic of Korea, for refractive surgery. METHODS: The prevalence of PVRA and their characteristics, including shape, location, presence of pigmentation, membrane, retinal breaks, and detachment, were evaluated. A logistic regression analysis was done to evaluate the risk factors of PVRA and the risk of retinal breaks or detachment among eyes with PVRA. RESULTS: Among 1966 eyes, 317 (16.1%) had PVRA, and 182 (57.4%) and 135 (42.6%) had focal and linear lesions, respectively. The risk of PVRA was increased with axial length of the eyes (odds ratio [OR], 1.238, 95% confidence interval [CI], 1.112-1.379, P < 0.001), corneal astigmatism (OR, 1.320, 95% CI, 1.148-1.519, P < 0.001), presence of discrete margins of different retinal reflectivity (DMDRR; indicating outer retinal disruption from abnormal vitreoretinal traction) (OR, 1.751, 95% CI, 1.334-2.300, P < 0.001), and posterior vitreous detachment (PVD) at the posterior pole of the retina (OR, 1.833, 95% CI, 1.352-2.485, P < 0.001). Among eyes with PVRA, patient age (OR, 1.063, 95% CI, 1.008-1.121, P = 0.025), linear lesions (OR, 15.234, 95% CI, 7.891-29.407, P < 0.001), and multiple lesions (OR, 3.432, 95% CI, 1.780-6.620, P < 0.001) were independently associated with the presence of retinal breaks or detachment. CONCLUSIONS: The follow-up for PVRA among young myopes should be personalized on the basis of their ocular characteristics, including asymmetric ocular expansion (axial length and astigmatism) and vitreoretinal interface status. The treatment plan for PVRA eyes should emphasize the greater risk of retinal breaks and detachment with increasing age and the presence of linear and multiple lesions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Association between Oral Active-Matrix Metalloproteinase-8 Levels and Subretinal Fibrosis among Wet Age-Related Macular Degeneration Patients.

PURPOSE: Periodontitis causes low-grade systemic inflammation and has been associated with elevated active-matrix metalloproteinase (aMMP-8) levels, blood-ocular barrier breakdown and a risk of wet age-related macular degeneration. To assess the association between aMMP-8 levels and macular status among patients with wet age-related macular degeneration (AMD). METHODS: Patients on anti-VEGF treatment for wet AMD were enrolled for oral aMMP-8 rinse test in Mehiläinen Private Hospital, Helsinki, Finland. Macular status was examined from spectral-domain optical coherence tomography (SD-OCT) scans by a medical retina specialist and aMMP-8 levels were analyzed with chairside point-of-care oral rinse (PerioSafe®) test and real-time quantitated by a dentist using the ORALyzer®- reader with a 10 ng/ml cut-off for aMMP-8 activity. RESULTS: Elevated aMMP-8 levels were found in 10 out of 32 patients. Age, gender, anti-VEGF (bevacizumab or aflibercept) distribution, cumulative number of anti-VEGF injections and treatment interval were comparable between patients with aMMP-8 levels below and above the point-of-care level. Macular status differed in regard to aMMP-8 activity; among patients with aMMP-8 levels below the point-of-care subretinal fibrosis was found in 6 out of 22 eyes, whereas among patients with aMMP-8 levels above the point-of-care subretinal fibrosis was found in 8 out of 10 eyes (p = 0.005). Respectively, the mean thickness of subretinal fibrosis at fovea was 19.5 ± 44.1 and 92.3 ± 78.3 µm (p = 0.018). No differences were found in the presence and in the area of geographic atrophy, or fluid distribution, whereas thicknesses of serous pigment epithelial detachment (65.5 ± 99.5 and 12.9 ± 27.9 µm, p = 0.038) and neuroretina (204.2 ± 57.8 µm and 143.0 ± 43.7 µm, p = 0.006) were greater in the eyes of patients with physiological aMMP-8 levels compared to those with elevated aMMP-8 levels. CONCLUSION: Elevated aMMP-8 levels may account for subretinal fibrosis formation in wet AMD.

Ethnicity, Progressive Keratoconus, and Outcomes after Corneal Cross-Linking in Southern Israel.

PURPOSE: To assess clinical outcomes of corneal cross-linking (CXL) intervention in a population diagnosed with progressive keratoconus. METHODS: This single-center retrospective cohort study included consecutive patients who underwent standard CXL or accelerated CXL for progressive keratoconus at a major teaching hospital in southern Israel between January 2015 and December 2019. Patients' medical files were reviewed, and pre-operative and post-operative data regarding demographics and clinical and tomographic characteristics were extracted and analyzed. RESULTS: This study included 166 patients (representing 198 eyes), out of which 98 patients (123 eyes) were ethnically Bedouin, and 68 patients (75 eyes) were ethnically Jewish. Overall, 126 patients (144 eyes) had a follow-up of at least 12 months (16.84 ± 5.76). The mean patient age was 20.62 ± 7.1 years old. There were significant baseline differences between the two ethnic groups in best-corrected visual acuity (BCVA; p < 0.001), uncorrected visual acuity (UCVA; p < 0.001), mean keratometry (p = 0.028), and corneal thickness (p < 0.001). Significant changes in BCVA, UCVA, and pachymetry parameters within each group were found after 12 months. Negative binomial regression analysis showed a maximal keratometry below 55D (RR = 1.247, p < 0.001), and a standard CXL procedure (RR = 1.147, p = 0.041) are significantly related to the stability of KC after 12 months. However, the effect size of the origin of patients is negligible (RR = 1.047, p = 0.47). CONCLUSIONS: In this study, the Bedouin population suffered from more progressive keratoconus when compared to the Jewish population. CXL was significantly effective in improving BCVA and UCVA in both groups after 12 months of follow-up. The effect size of the origin of patients on the stability of KC was found to be negligible.

Technical failure rates for biometry between swept-source and older-generation optical coherence methods: a review and meta-analysis.

PURPOSE: Precise ocular measurements are fundamental for achieving excellent target refraction following both cataract surgery and refractive lens exchange. Biometry devices with swept-source optical coherence tomography (SS-OCT) employ longer wavelengths (1055-1300 nm) in order to have better penetration through opaque lenses than those with partial coherence interferometry (PCI) or low-coherence optical reflectometry (LCOR) methods. However, to date a pooled analysis showing the technical failure rate (TFR) between the methods has not been published. The aim of this study was to compare the TFR in SS-OCT and in PCI/LCOR biometry. METHODS: PubMed and Scopus were used to search the medical literature as of Feb 1, 2022. The following keywords were used in various combinations: optical biometry, partial coherence interferometry, low-coherence optical reflectometry, swept-source optical coherence tomography. Only clinical studies referring to patients undergoing routine cataract surgery, and employing at least two (PCI or LCOR vs. SS-OCT) optical methods for optical biometry in the same cohort of patients were included. RESULTS: Fourteen studies were included in the final analysis, which presented results of 2,459 eyes of at least 1,853 patients. The overall TFR of all included studies was 5.47% (95% confidence interval [CI]: 3.66-8.08%; overall I2 = 91.49%). The TFR was significantly different among the three methods (p < 0.001): 15.72% for PCI (95% CI: 10.73-22.46%; I2 = 99.62%), 6.88% for LCOR (95% CI: 3.26-13.92%; I2 = 86.44%), and 1.51% for SS-OCT (95% CI: 0.94-2.41%; I2 = 24.64%). The pooled TFR for infrared methods (PCI and LCOR) was 11.12% (95% CI: 8.45-14.52%; I2 = 78.28%), and was also significantly different to that of SS-OCT: 1.51% (95% CI: 0.94-2.41%; I2 = 24.64%; p < 0.001). CONCLUSIONS: A meta-analysis of the TFR of different biometry methods highlighted that SS-OCT biometry resulted in significantly decreased TFR compared to PCI/LCOR devices.

The Effect of Blue-Light Filtering Intraocular Lenses on the Development and Progression of Glaucoma.

PRCIS: Among patients who underwent uneventful cataract surgery, an advantage was seen to blue-light filtering (BLF) intraocular lenses (IOLs) in terms of glaucoma-free survival and glaucoma procedure-free survival. Among patients with preexisting glaucoma, no advantage was seen. PURPOSE: To assess the effect of BLF IOLs on the development and progression of glaucoma after cataract surgery. PATIENTS AND METHODS: A retrospective cohort study of patients who underwent uneventful cataract surgery between 2007 and 2018 at Kymenlaakso Central Hospital, Finland. Survival analyses for the overall risk of developing glaucoma or undergoing glaucoma procedures were assessed between patients who received a BLF IOL (SN60WF) and a non-BLF IOL (ZA9003 and ZCB00). A separate analysis was performed on patients with preexisting glaucoma. RESULTS: Included 11,028 eyes of 11,028 patients with a mean age of 75 ± 9 years (62% females). The BLF IOL was used in 5188 eyes (47%) and the non-BLF IOL in 5840 eyes (53%). During the follow-up (mean: 55 ± 34 mo), 316 cases of glaucoma were diagnosed. Glaucoma-free survival rates showed an advantage to the BLF IOL ( P = 0.036). In a Cox regression analysis controlling for age and sex the use of a BLF IOL was again associated with a lower ratio of glaucoma development (hazard ratio:0.778; 95% CI: 0.621-0.975). Furthermore, glaucoma procedure-free survival analysis revealed an advantage to the BLF IOL (hazard ratio:0.616; 95% CI: 0.406-0.935). Among 662 cases, which already had glaucoma at the time of surgery, no significant differences were seen in any outcome. CONCLUSIONS: Among a large cohort of patients who underwent cataract surgery, the use of BLF IOLs was associated with favorable glaucoma outcomes compared with the use of non-BLF IOLs. Among patients with preexisting glaucoma, no significant advantage was seen.

Association of clear vs blue-light filtering intraocular lenses with mental and behavioral disorders and diseases of the nervous system among patients receiving bilateral cataract surgery.

PURPOSE: To analyze new-onset mental and behavioral disorders and nervous system diseases in patients with cataract implanted with either non-blue-light filtering (BLF) or BLF intraocular lenses (IOLs) in both eyes. SETTING: Department of Ophthalmology, Kymenlaakso Central Hospital, Kotka, Finland. DESIGN: A retrospective registry-based cohort study of patients operated between September 2007 and December 2018 who were followed until December 2021. We included 4986 patients who underwent bilateral cataract surgery. METHODS: Patients were implanted with either non-BLF IOLs (N = 2609) or BLF IOLs (N = 2377) in both eyes. Follow-up before the first-eye surgery and between the first-eye and the second-eye surgery was performed to acknowledge the preexisting disorders and diseases. After the second-eye surgery, the groups were analyzed for the new-onset mental and behavioral disorders and diseases of the nervous system subcategorized by the International Classification of Diseases codes. RESULTS: 1707 male and 3279 female patients, aged 73.2 ± 8.6 years at the first-eye surgery and 74.3 ± 8.8 years at the second-eye surgery, were identified. In univariate log-rank tests, the use of BLF IOLs showed no association in overall new-onset disorders or diseases over non-BLF IOLs, in any subtype diagnosis codes except for sleep disorders, which favored BLF IOLs ( P = .003). A multivariate analysis adjusted for age and sex identified no associations in any new-onset disorders or diseases. Multivariate analysis of sleep disorders showed a nonsignificant advantage for BLF-IOLs (hazard ratio 0.756, 95% CI 0.534-1.070, P = .114). CONCLUSIONS: BLF IOLs were not associated with mental and behavioral disorders or diseases of the nervous system.