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.

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.

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.

Clinical comparison of manual and laser-cut corneal tunnel for intrastromal air injection in femtosecond laser-assisted deep anterior lamellar keratoplasty (DALK).

PURPOSE: The most crucial step in deep anterior lamellar keratoplasty (DALK) is to achieve a bare Descemet's membrane. We aimed to assess a new femtosecond laser software that allows for a precise intrastromal tunnel creation for big bubble (BB) air injection using a real-time microscope-integrated optical coherence tomography. MATERIALS AND METHODS: A retrospective review of 61 eyes of 61 patients with keratoconus. Before introducing the new software update, DALK was performed using a partial-assisted femtosecond laser (partial-thickness circular cut followed by a lamellar cut) with manual intrastromal tunnel creation (partial FS-DALK group). After the software update, the femtosecond laser created the intrastromal tunnel (full FS-DALK group). RESULTS: In the full FS-DALK group, the BB's formation was significantly higher (64.3% vs. 36.4%, p = 0.04), and surgery time was shorter (21.8 ± 5.1 vs. 25.6 ± 6.8 min, p = 0.025) than in the partial FS-DALK. Penetrating keratoplasty conversion rate (7.1% vs. 15.1%, p = 0.432) was similar between the groups. Both groups showed statistically significant improvement in uncorrected and corrected distance visual acuity, central corneal thickness, surface asymmetry, and regularity indices. Endothelial cell density loss at 12 and 18 months was lower in the full compared with the partial FS-DALK group (12 months:10.0% vs. 16; 18 months: 10.7 vs. 16.5%, p < 0.001 for both comparisons). CONCLUSIONS: Creating the intrastromal guiding tunnel using FS laser for air injection resulted in a higher rate of BB formation, reduced long-term endothelial cell loss, and operating room time.

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.

Evaluation of IOL power calculation with the Kane formula for pediatric cataract surgery.

PURPOSE: To assess the accuracy of the Kane formula for intraocular lens (IOL) power calculation in the pediatric population. METHODS: The charts of pediatric patients who underwent cataract surgery with in-the-bag IOL implantation with one of two IOL models (SA60AT or MA60AC) between 2012 and 2018 in The Hospital for Sick Children, Toronto, Ontario, CanFada, were retrospectively reviewed. The accuracy of IOL power calculation with the Kane formula was evaluated in comparison with the Barrett Universal II (BUII), Haigis, Hoffer Q, Holladay 1, and Sanders-Retzlaff-Kraff Theoretical (SRK/T) formulas. RESULTS: Sixty-two eyes of 62 patients aged 6.2 (IQR 3.2-9.2) years were included. The SD values of the prediction error obtained by Kane (1.38) were comparable with those by BUII (1.34), Hoffer Q (1.37), SRK/T (1.40), Holaday 1 (1.41), and Haigis (1.50), all p > 0.05. A significant difference was observed between the Hoffer Q and Haigis formulas (p = 0.039). No differences in the median and mean absolute errors were found between the Kane formula (0.54 D and 0.91 ± 1.04 D) and BUII (0.50 D and 0.88 ± 1.00 D), Hoffer Q (0.48 D and 0.88 ± 1.05 D), SRK/T (0.72 D and 0.97 ± 1.00 D), Holladay 1 (0.63 D and 0.94 ± 1.05 D), and Haigis (0.57 D and 0.98 ± 1.13 D), p = 0.099. CONCLUSION: This is the first study to investigate the Kane formula in pediatric cataract surgery. Our results place the Kane among the noteworthy IOL power calculation formulas in this age group, offering an additional means for improving IOL calculation in pediatric cataract surgery. The heteroscedastic statistical method was first implemented to evaluate formulas' predictability in children.

Validation of the multi-metric D-index change in the assessment of keratoconus progression.

PURPOSE: To validate the effectiveness of the multi-metric D-index by Pentacam in detecting keratoconus (KC) progression. MATERIALS AND METHODS: This was a retrospective study of KC patients at the Rabin Medical Center, Petah Tikva, Israel, during 2016-2018 with at least two corneal tomography examinations six months apart. Agreement between clinical diagnosis of progression (1.5D increase in mean keratometric value, 1D increase in Kmax, a 5% decrease in central corneal thickness (CCT), worsening of visual acuity by more than one line, or deterioration of manifest corneal astigmatism > 1.5D) and the D-index was evaluated. Receiver operating characteristic (ROC) analysis was used to find the D-index's optimal cutoff value to show progression. RESULTS: We included KC eyes in the stable group (N = 7) and the progression group (N = 54). Patient demographics and tomographic parameters at baseline were similar between the groups. The D-index change was significantly higher in the progression group than in the stable group (median + 1 and 0.0, respectively, p = 0.024). Based on the ROC analysis, the optimal D-index cutoff change within at least six months was 0.32 (59.3% sensitivity and 100% specificity (area under the curve [AUC] = 0.771, Youden = 0.592). Subjects with a D-index change above this value had a 21.1-fold increase in odds for corneal ectasia progression requiring CXL (OR: 21.1, 95%CI 1.17-398.8, p = 0.038). CONCLUSION: The multi-metric D-index can serve as a clinically feasible parameter to detect KC progression and guide patients' referral for further interventions.

The Effect of Blue-Light Filtering Intraocular Lenses on the Development and Progression of Neovascular Age-Related Macular Degeneration.

PURPOSE: To assess the effect of blue-light filtering (BLF) intraocular lenses (IOLs) on the prevention of neovascular age-related macular degeneration (nAMD) after cataract surgery. DESIGN: Cohort study. PARTICIPANTS: Patients who underwent uneventful cataract surgery between 2007 and 2018 at the Ophthalmology Unit of Kymenlaakso Central Hospital, Kotka, Finland. METHODS: Subsequent nAMD rates were compared between patients who received BLF IOLs and those who received non-BLF IOLs. Kaplan-Meier and Cox regression analyses for the overall risk of nAMD developing were assessed. Best-corrected visual acuity (BCVA), foveal thickness, treatment interval, and total number of intravitreal injections were secondary outcomes. A separate analysis was performed on patients with pre-existing nAMD to assess the effect of BLF IOLs on nAMD progression. A single eye of each patient was included. MAIN OUTCOME MEASURE: Neovascular age-related macular degeneration-free survival. RESULTS: Included were 11 397 eyes of 11 397 patients with a mean age of 75.4 ± 8.3 years (62.5% women). The BLF IOL was used in 5425 eyes (47.6%), and the non-BLF IOL was used in 5972 eyes (52.4%). During follow-up (BLF IOL group, 55.2 ± 34.1 months; non-BLF IOL group, 50.5 ± 30.1 months; P < 0.001), 164 cases of new-onset nAMD were recorded (BLF group, n = 88; non-BLF group, n = 76). The nAMD-free survival was similar between the groups (P = 0.465, log-rank test). In a Cox regression analysis controlling for age, gender, and a documented diagnosis of macular degeneration, the use of a BLF IOL was not predictive of nAMD development (hazard ratio [HR], 1.075; 95% confidence interval [CI], 0.79-1.47; P = 0.652). In nAMD patients, secondary clinical outcomes at 1 year were comparable for BCVA (0.57 ± 0.4 logarithm of the minimum angle of resolution vs. 0.45 ± 0.4 logarithm of the minimum angle of resolution; P = 0.136), foveal thickness (285 ± 109 µm vs. 299 ± 103µm; P = 0.527), number of anti-vascular endothelial growth factor injections (6.5 ± 2.5 vs. 6.2 ± 2.7; P = 0.548), and treatment interval (7.5 ± 2.4 weeks vs. 8.1 ± 2.4 weeks; P = 0.271) for BLF and non-BLF IOLs, respectively. Similarly to patients in whom nAMD developed after the surgery, among patients with nAMD before surgery (BLF, n = 71; non-BLF, n = 74), the clinical outcomes again were comparable (all P > 0.05). CONCLUSIONS: In a large cohort of patients who underwent cataract surgery, the use of a BLF IOL resulted in no apparent advantage over a non-BLF IOL in the incidence of nAMD or its progression, nor in clinical variables related to nAMD severity.

Long-term effects of intravitreal bevacizumab and aflibercept on intraocular pressure in wet age-related macular degeneration.

BACKGROUND: To evaluate the incidence of sustained elevation of intraocular pressure (SE-IOP) associated with intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) bevacizumab and aflibercept in patients with wet age-related macular degeneration (wAMD). METHODS: A retrospective cohort study consisting of 120 eyes from 120 patients with anti-VEGF treatment for wAMD. Three different anti-VEGF groups were considered: i) 71 cases receiving bevacizumab only, ii) 49 cases receiving bevacizumab before switch to aflibercept, iii) 49 cases after switch to aflibercept. 120 uninjected fellow eyes served as controls. SE-IOP was defined as an increase from baseline ≥5 mmHg on 2 consecutive follow-up visits. The incidence of SE-IOP was analysed using exact Poisson tests and survival analysis. The time course of IOP was evaluated with linear mixed effect modelling. RESULTS: In total, 6 treated eyes (2.38% incidence per eye-year) and 9 fellow eyes (3.58% incidence per eye-year) developed SE-IOP, and survival analysis showed no statistically significant difference (p = 0.43). Furthermore, the incidence of SE-IOP did not differ between the three anti-VEGF groups. Comparing the injected eyes of patients under 70 years to those of patients over 70 years, there was a statistically significant difference in survival without SE-IOP (incidence of 16.7% vs 0.7%, respectively, p < 0.0001). CONCLUSION: Intravitreal anti-VEGF injections were not associated with sustained elevation of IOP. These results do not support the claim that repeated anti-VEGF injections could elevate IOP.

Interdigitation and Ellipsoid Zones Disruption Correlate with Visual Outcomes among Treatment-Naive Patients with Diabetic Macular Edema.

INTRODUCTION: We have recently shown that defects in interdigitation and ellipsoid zones (IZ and EZ) can predict response to anti-VEGF therapy in a small group of treatment-naive diabetic macular edema (DME) patients. The aim of the current study is to further evaluate this association in a larger study group of patients over a longer follow-up time. METHODS: Thirty eyes of 30 treatment-naive DME patients were analyzed in this retrospective study. The integrity of foveal IZ and EZ was evaluated using optical coherence tomography at the diagnosis of DME and following anti-VEGF injections. The defect size was correlated with best-corrected visual acuity (BCVA) and central macular thickness (CMT). RESULTS: The mean patients' age at baseline was 63.0 ± 10.0 years. Patients underwent 3.9 ± 2.9 anti-VEGF injections for a mean of 9.1 ± 4.8 months. Following treatment, the mean Snellen visual acuity (VA) improved from 20/52 to 20/44 (p = 0.05), CMT decreased from 432.5 ± 141.4 µm to 375.2 ± 121.4 µm (p = 0.05) and IZ/EZ defect size decreased from 259.83 ± 375.94 µm to 65.34 ± 143.97 µm (p = 0.001). In patients with no IZ/EZ defects at baseline, the mean Snellen VA was better when compared to those with IZ/EZ defects (20/36 vs. 20/70, p = 0.031). The number of eyes with IZ/EZ defects decreased from 17 (57%) at baseline to 6 (20%) at end of follow-up (p < 0.01). BCVA gain correlated with IZ/EZ defect size reduction (r = 0.41, p = 0.02) but not with improvement in CMT (r = 0.28, p = 0.121). CONCLUSIONS: IZ/EZ defect size correlated not only with baseline BCVA but also predicted the change in BCVA after anti-VEGF treatment. Possible future automatic measurement of IZ/EZ defect size might prove helpful for the evaluation of treatment response.

Agreement of Corneal Endothelial Cell Analysis Between Konan-Noncon Robo SP-6000 and Tomey EM-3000 Specular Microscopes in Healthy Subjects.

PURPOSE: To compare corneal endothelium parameters taken by two common noncontact specular microscopes in healthy subjects. METHODS: Healthy participants visiting the outpatient eye clinic at the Rabin Medical Center, Petah Tikva, Israel, were recruited prospectively. All participants underwent three consecutive corneal endothelial cell photographs with both the Konan-Noncon Robo SP-6000 and the Tomey EM-3000 specular microscopes. Endothelial cell density (ECD) was evaluated using the manual center technique in both machines. Bland-Altman graphs were used to assess the agreement between the devices, and intraclass correlation coefficient (ICC) served to assess intraobserver variability for each device. RESULTS: Recruited were 49 healthy subjects with a mean age of 48.9±15.6 years, 49 right eyes were included. The mean ECD was comparable between the Tomey EM-3000 and the Konan-Noncon Robo SP-6000 (2,713.2±242.4 vs. 2,700.8±300.5 cells/mm2, respectively, P=0.47) with a mean difference of 12.4 cells/mm2 (0.67%), a mean ECD absolute difference of 93.3 cells/mm2, and low 95% limits of agreement of -222.0 to +246.9 cells/mm2. A folded empirical distribution function curve showed that all differences fell within 525.4 cells/mm2, centered around a median of 13.3 cells/mm2. Intraclass correlation coefficient was high for both the Konan-Noncon Robo SP-6000 (0.93, 95% confidence interval [CI]: 0.89-0.95) and the Tomey EM-3000 (0.88, 95% CI: 0.82-0.93). CONCLUSIONS: The difference in endothelial cell measurements between the Konan SP-6000 and the Tomey EM-3000 specular microscopes through the center and the L-count analyzing techniques, respectively, is clinically small and not statistically significant. Nevertheless, caution should be taken when used interchangeably because ECD difference between the two machines can be as high as 525.4 cells/mm2.

Comparison of keratometry data using handheld and table-mounted instruments in healthy adults.

PURPOSE: To compare keratometry data between the handheld Retinomax K-plus 3 and the table-mounted IOLMaster 700. METHODS: Healthy adult volunteers were prospectively recruited to the study. All participants underwent 3 consecutive keratometry measurements using the Retinomax K-plus 3 and a single biometry assessment using the IOLMaster 700. Differences between the Retinomax K-plus 3 and the IOLMaster 700 were assessed using Wilcoxon test for paired samples, Spearman correlation, Bland-Altman and mountain plots. RESULT: Twenty-eight healthy subjects with a median age of 37 years (interquartile range (IQR) 28-44 years) were included in the study. The median mean keratometry (mean K) reading was higher using the Retinomax K-plus 3 (44.04D; IQR 42.96-45.61D) compared to the IOLMaster 700 (43.78D; IQR 43.22-44.90D, p < 0.01), with a mean difference of 0.18D (95% confidence interval (CI) 0.11-0.23D). Mean K readings were highly correlated between the 2 devices (r = 0.995, p < 0.01). Bland-Altman plots showed 95% limits of agreement between -0.14D and 0.49D. Frequency histogram of mean K reading differences between the Retinomax K-plus 3 and the IOLMaster 700 showed that 56% of cases were between ± 0.2D, 93% of cases were between ± 0.4D and all cases were between ± 0.5D. Mean corneal astigmatism measurement was higher using the Retinomax K-plus 3 (1.01 ± 0.40D) compared to the IOLMaster 700 (0.77 ± 0.36D), with a mean difference of 0.23 ± 0.37D (p < 0.01) between the devices. CONCLUSIONS: A good agreement exists between the Retinomax K-plus 3 and the IOLMaster 700 regarding keratometry readings. This enables cataract surgeons to safely use the Retinomax K-plus 3 device when indicated.

Donor Simvastatin Treatment in Heart Transplantation.

BACKGROUND: Ischemia-reperfusion injury may compromise the short-term and long-term prognosis after heart transplantation. Experimental studies show that simvastatin administered to the organ donor is vasculoprotective and inhibits cardiac allograft ischemia-reperfusion injury. METHODS: Eighty-four multiorgan donors were randomly assigned to receive 80 mg of simvastatin (42 donors) via nasogastric tube after declaration of brain death and upon acceptance as a cardiac donor, or to receive no simvastatin (42 donors). The primary efficacy end point was postoperative plasma troponin T and I levels during the first 24 hours after heart transplantation. Secondary end points included postoperative hemodynamics, inflammation, allograft function, rejections and rejection treatments, and mortality. Results: Organ donor simvastatin treatment significantly reduced the heart recipient plasma levels of troponin T by 34% (14 900 ± 12 100 ng/L to 9800 ± 7900 ng/L, P=0.047), and troponin I by 40% (171 000 ± 151 000 ng/L to 103 000 ± 109 000 ng/L, P=0.023) at 6 hours after reperfusion, the levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) by 36% (32 800 ± 24 300 ng/L to 20 900 ± 15 900 ng/L; P=0.011) at 1 week, and the number of rejection treatments with hemodynamic compromise by 53% within the first 30 days (P=0.046). Donor simvastatin treatment did not affect donor lipid levels but was associated with a specific transplant myocardial biopsy gene expression profile, and a decrease in recipient postoperative plasma levels of CXCL10 (C-X-C motif chemokine 10), interleukin-1α, placental growth factor, and platelet-derived growth factor-BB. Postoperative hemodynamics, biopsy-proven acute rejections, and mortality were similar. No adverse effects were seen in recipients receiving noncardiac solid organ transplants from simvastatin-treated donors. CONCLUSIONS: Donor simvastatin treatment reduces biomarkers of myocardial injury after heart transplantation, and-also considering its documented general safety profile-may be used as a novel, safe, and inexpensive adjunct therapy in multiorgan donation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01160978.

Multifocal intraocular lenses and retinal diseases.

PURPOSE: Multifocal intraocular lenses (MIOLs) are often discouraged in patients with or at risk of retinal disorders (including diabetic retinopathy, age-related macular degeneration, and epiretinal membranes), as MIOLs are believed to reduce contrast sensitivity (CS). Concerns with MIOLs have also been raised in individuals with visual field defects, fixation instability or eccentric preferred retinal locations. The aim of this study is to review the influence of MIOL on quality of vision in patients with retinal diseases. METHODS: We reviewed the PubMed and Web of Science databases to identify relevant studies using the following keywords: multifocal intraocular lens, cataract surgery, cataract extraction, lens exchange, diabetic retinopathy, age-related macular degeneration, and contrast sensitivity. RESULTS: Studies evaluating CS in MIOLs present conflicting results: MIOLs either did not influence CS or resulted in worse performance under low-illuminance conditions and higher spatial frequencies when compared to monofocal IOLs. Nevertheless, MIOLs preserved CS levels within the age-matched normal range. Two studies reported that patients with concurrent retinal diseases receiving a MIOL, both unilaterally and bilaterally, reported a significant improvement in visual-related outcomes. Individuals with a monofocal IOL in one eye and a MIOL in the fellow eye reported greater subjective satisfaction with the MIOL. CONCLUSION: We were unable to find evidence suggesting that patients with retinal diseases should be advised against MIOLs. Nevertheless, more research is needed to address the aforementioned concerns and to optimize the use of MIOLs in eyes with retinal disease.

Association between intraocular lens diopter and posterior capsular opacification.

IMPORTANCE: Posterior capsular opacification (PCO) is the most common complication after cataract surgery. BACKGROUND: We aimed to assess the relationship between intraocular lens (IOL) diopter and formation of PCO among a consecutive real-world registry. DESIGN: Cohort study. PARTICIPANTS: Included were 14 264 consecutive cases of uncomplicated cataract surgery performed during 2014 to 2018 in Helsinki University Hospital in Finland. METHODS: Nd:YAG capsulotomies were used as an estimate of clinically significant PCO. A single eye of each patient and a single type of IOL were included. MAIN OUTCOME MEASURE: Nd:YAG posterior capsulotomy free survival. RESULTS: Mean age was 73.2 ± 9.9 years and 61.8% were female. Mean follow-up time was 25.4 ± 16.8 months. Overall PCO rates were 1.1% at 1-year, 3.0% at 2-year, 7.1% at 3-year and 10.2% at 4-year. Patients with IOL diopters (D) in the lower quartile (≤20.0 D) had significantly higher rates of PCO (1.3% at 1-year, 4.4% at 2-years, 9.4% at 3-years and 14.2% at 4-years, P < .001). A logistic regression model showed increased risk for PCO formation with lower diopter IOLs; for ≤20.0 D: OR 1.343 (95% CI: 1.132-1.593), for ≤10.0 D: OR 2.409 (95% CI 1.203-4.287), P < .001 for all comparisons. In a multivariant regression accounting for possible confounders, results remained consistent. CONCLUSIONS AND RELEVANCE: Among a cohort of patients undergoing cataract surgery, use of lower diopter IOLs was associated with increased incidence of clinically significant PCO. Research into IOL biomechanics to decrease PCO may be warranted especially in lower diopter IOLs.

Expression of VEGFA-regulating miRNAs and mortality in wet AMD.

MicroRNAs (miRNAs) regulate gene expression; many of them act in the retinal pigment epithelium (RPE), and RPE degeneration is known to be a critical factor in age-related macular degeneration (AMD). Repeated injections with anti-VEGFA (vascular endothelial growth factor A) are the only effective therapy in wet AMD. We investigated the correlation between the expression of 18 miRNAs involved in the regulation of the VEGFA gene in serum of 76 wet AMD patients and 70 controls. Efficacy of anti-VEGFA treatment was evaluated by counting the number of injections delivered up to 12 years. In addition, we compared the relative numbers of deaths in patient with AMD and control groups. We observed a decreased expression of miR-34-5p, miR-126-3p, miR-145-5p and miR-205-5p in wet AMD patients as compared with controls. These miRNAs are involved in the regulation of angiogenesis, cytoprotection and protein clearance. No miRNA was significantly correlated with the treatment outcome. Wet AMD patients had greater mortality than controls, and their survival was inversely associated with the number of anti-VEGFA injections per year. No association was observed between miRNA expression and mortality. Our study emphasizes the need to clarify the role of miRNA regulation in AMD pathogenesis.

Hypoxia-inducible factor controls immunoregulatory properties of myeloid cells in mouse cardiac allografts - an experimental study.

Hypoxia-inducible factors (HIFs) play a critical role in inflammatory properties of myeloid-derived cells. The effect of HIFs on myeloid-derived cell functions in organ transplantation remains unknown, however. We transplanted hearts into transgenic mice with myeloid cell-targeted deletions of HIF-1α or its negative regulator von Hippel-Lindau (VHL) to investigate the effects of HIF-1α inactivation or HIF pathway activation, respectively, on ischemia-reperfusion injury (IRI) and acute rejection. Deletion of VHL in myeloid cells enhanced mRNA expression of anti-inflammatory genes IDO, Arg-1, and HO-1 in vitro. In vivo, VHL-/- myeloid-derived cells of allograft recipients alleviated IRI and acute rejection, evidenced by reduced cardiomyocyte damage, decreased proinflammatory cytokine mRNA levels, and absence of inflammatory infiltrate at 5 days after transplantation. Ultimately, allograft survival was significantly prolonged. In vitro, VHL-/- myeloid-derived cells dose-dependently inhibited T-cell proliferation. Myeloid cells with HIF-1α-deletion retained proinflammatory qualities in vitro and in vivo. Deletion of VHL in myeloid cells of nonimmunosuppressed cardiac allograft recipients reduced myocardial injury and acute rejection. We suggest that HIF transcription factors induce a regulatory phenotype in myeloid-derived cells, which may be harnessed as a novel therapeutic strategy to regulate immune responses after heart transplantation.

Dual antiplatelet and anticoagulant APAC prevents experimental ischemia-reperfusion-induced acute kidney injury.

BACKGROUND: Renal ischemia-reperfusion predisposes to acute kidney injury (AKI) and mortality. APAC, mast cell heparin proteoglycan mimetic is a potent dual antiplatelet and anticoagulant inhibiting thrombosis in several vascular models. METHODS: Clinically relevant (0.06 and 0.13 mg/kg) and high (0.32 and 7.3 mg/kg) heparin doses of APAC and unfractionated heparin (UFH) were administered i.v. in pharmacological studies. Antithrombotic action of APAC and UFH was assessed with platelet aggregation to collagen, activated partial thromboplastin (APTT) and prothrombin (PT) times. Pharmacodynamics of [64Cu]-APAC or -UFH were monitored by PET/CT. Next, APAC and UFH doses (0.06 and 0.13 mg/kg) were i.v. administered 10 min prior to renal ischemia-reperfusion injury (IRI) in rats. RESULTS: APAC in contrast to UFH inhibited platelet aggregation. During 0.06 and 0.13 mg/kg dose regimens APTT and PT remained at baseline, but at the high APTT prolonged fourfold to sixfold. Overall bio-distribution and clearance of APAC and UFH were similar. After bilateral 30-min renal artery clamping, creatinine, urea nitrogen and neutrophil gelatinase-associated lipocalin concentrations and histopathology indicated faster renal recovery by APAC (0.13 mg/kg). APAC, unlike UFH, prevented expression of innate immune ligand hyaluronan and tubulointerstitial injury marker Kim-1. Moreover, in severe bilateral 1-h renal artery clamping, APAC (0.13 mg/kg) prevented AKI, as demonstrated both by biomarkers and survival. Compatible with kidney protection APAC reduced the circulating levels of vascular destabilizing and pro-inflammatory angiopoietin-2 and syndecan-1. No tissue bleeding ensued. CONCLUSION: APAC and UFH were similarly eliminated via kidneys and liver. In contrast to UFH, APAC (0.13 mg/kg) was reno-protective in moderate and even severe IRI by attenuating vascular injury and innate immune activation.