Long-Term Clinically Significant Posterior Capsular Opacification Development Pattern in Eyes Implanted with an Aspheric Monofocal Intraocular Lens with a Square Optic Edge.

PURPOSE: To analyse the posterior capsular opacification (PCO) development pattern in the long term in eyes implanted with a monofocal intraocular lens (IOL) with a square edge all around the optic. METHODS: Longitudinal retrospective study is data analyzed from a total of 7059 eyes from 4764 patients (mean age: 75.8 years) undergoing cataract surgery with implantation of an aspheric monofocal IOL (Bi-Flex HL 677AB/677P, Medicontur, Budapest, Hungary). These data were retrospectively collected using the electronic medical record of the hospitals involved. Nd : YAG capsulotomy rates were calculated per year during a follow-up of more than 10 years. The Kaplan-Meier analysis was used to establish the transparent capsule survival rate. RESULTS: The Nd : YAG capsulotomy rate increased from 1.1% at 1 year postoperatively to 17.2% at 5 years after surgery. No significant differences were found between eyes with and without capsulotomy in terms of age (p = 0.202), gender (p = 0.061), type of anaesthesia used (p = 0.128), and presence of conditions such as hard cataract (p = 0.111) or pseudoexfoliation (p = 0.137). IOL power was significantly lower in those eyes of patients requiring Nd : YAG capsulotomy during the follow-up (p < 0.001). Significantly more eyes implanted with the preloaded model of the IOL required capsulotomy (p < 0.001). Mean survival time and rate were 9.38 years and 85.9%, respectively. CONCLUSIONS: Most eyes undergoing cataract with implantation of the Bi-Flex IOL do not develop a clinically significant PCO requiring Nd : YAG capsulotomy in the long term. IOL material and design may be the main factors accounting for this finding.

Evaluation of M2-like macrophage enrichment after diffuse traumatic brain injury through transient interleukin-4 expression from engineered mesenchymal stromal cells.

BACKGROUND: Appropriately modulating inflammation after traumatic brain injury (TBI) may prevent disabilities for the millions of those inflicted annually. In TBI, cellular mediators of inflammation, including macrophages and microglia, possess a range of phenotypes relevant for an immunomodulatory therapeutic approach. It is thought that early phenotypic modulation of these cells will have a cascading healing effect. In fact, an anti-inflammatory, "M2-like" macrophage phenotype after TBI has been associated with neurogenesis, axonal regeneration, and improved white matter integrity (WMI). There already exist clinical trials seeking an M2-like bias through mesenchymal stem/stromal cells (MSCs). However, MSCs do not endogenously synthesize key signals that induce robust M2-like phenotypes such as interleukin-4 (IL-4). METHODS: To enrich M2-like macrophages in a clinically relevant manner, we augmented MSCs with synthetic IL-4 mRNA to transiently express IL-4. These IL-4 expressing MSCs (IL-4 MSCs) were characterized for expression and functionality and then delivered in a modified mouse TBI model of closed head injury. Groups were assessed for functional deficits and MR imaging. Brain tissue was analyzed through flow cytometry, multi-plex ELISA, qPCR, histology, and RNA sequencing. RESULTS: We observed that IL-4 MSCs indeed induce a robust M2-like macrophage phenotype and promote anti-inflammatory gene expression after TBI. However, here we demonstrate that acute enrichment of M2-like macrophages did not translate to improved functional or histological outcomes, or improvements in WMI on MR imaging. To further understand whether dysfunctional pathways underlie the lack of therapeutic effect, we report transcriptomic analysis of injured and treated brains. Through this, we discovered that inflammation persists despite acute enrichment of M2-like macrophages in the brain. CONCLUSION: The results demonstrate that MSCs can be engineered to induce a stronger M2-like macrophage response in vivo. However, they also suggest that acute enrichment of only M2-like macrophages after diffuse TBI cannot orchestrate neurogenesis, axonal regeneration, or improve WMI. Here, we also discuss our modified TBI model and methods to assess severity, behavioral studies, and propose that IL-4 expressing MSCs may also have relevance in other cavitary diseases or in improving biomaterial integration into tissues.

External validation of cut-off points for foveal thickness taking into account the intraretinal fluid using optical coherence tomography to diagnose diabetic macular oedema.

BACKGROUND: In late 2015, cut-off points were published for foveal thickness to diagnose diabetic macular oedema taking into account the presence of intraretinal fluid using optical coherence tomography (OCT) in primary care patients (90 µm in the presence of intraretinal fluid and 310 µm otherwise). METHODS: This cross-sectional observational study was carried out on 134 eyes of diabetic patients treated in specialised ophthalmology services in a Spanish region in 2012-2013, to externally validate the aforementioned cut-off points. The main variable (Clinical Standard) was the diagnosis of macular oedema through indirect ophthalmoscopy and posterior segment slit-lamp biomicroscopy. As validation variables, both the foveal thickness and the presence of intraretinal fluid obtained by OCT were used. Validation was performed using bootstrapping by calculating the area under the ROC curve (AUC), sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR). RESULTS: Forty-one eyes presented diabetic macular oedema (30.6%). The bootstrapping validation parameters were: AUC, 0.88; sensitivity, 0.75; specificity, 0.95; PLR, 14.31; NLR, 0.26. These values were very similar to those of the original publication. CONCLUSION: We have externally validated in specialised care patients the cut-off points published for the diagnosis of diabetic macular oedema. We suggest that others carry out validation studies in their communities.

A predictive screening tool to detect diabetic retinopathy or macular edema in primary health care: construction, validation and implementation on a mobile application.

The most described techniques used to detect diabetic retinopathy and diabetic macular edema have to be interpreted correctly, such that a person not specialized in ophthalmology, as is usually the case of a primary care physician, may experience difficulties with their interpretation; therefore we constructed, validated and implemented as a mobile app a new tool to detect diabetic retinopathy or diabetic macular edema (DRDME) using simple objective variables. We undertook a cross-sectional, observational study of a sample of 142 eyes from Spanish diabetic patients suspected of having DRDME in 2012-2013. Our outcome was DRDME and the secondary variables were: type of diabetes, gender, age, glycated hemoglobin (HbA1c), foveal thickness and visual acuity (best corrected). The sample was divided into two parts: 80% to construct the tool and 20% to validate it. A binary logistic regression model was used to predict DRDME. The resulting model was transformed into a scoring system. The area under the ROC curve (AUC) was calculated and risk groups established. The tool was validated by calculating the AUC and comparing expected events with observed events. The construction sample (n = 106) had 35 DRDME (95% CI [24.1-42.0]), and the validation sample (n = 36) had 12 DRDME (95% CI [17.9-48.7]). Factors associated with DRDME were: HbA1c (per 1%) (OR = 1.36, 95% CI [0.93-1.98], p = 0.113), foveal thickness (per 1 µm) (OR = 1.03, 95% CI [1.01-1.04], p < 0.001) and visual acuity (per unit) (OR = 0.14, 95% CI [0.00-0.16], p < 0.001). AUC for the validation: 0.90 (95% CI [0.75-1.00], p < 0.001). No significant differences were found between the expected and the observed outcomes (p = 0.422). In conclusion, we constructed and validated a simple rapid tool to determine whether a diabetic patient suspected of having DRDME really has it. This tool has been implemented on a mobile app. Further validation studies are required in the general diabetic population.

Detection of diabetic macular oedema: validation of optical coherence tomography using both foveal thickness and intraretinal fluid.

UNLABELLED: No studies have yet evaluated jointly central foveal thickness (CFT) and the presence of intraretinal fluid (PIF) to diagnose diabetic macular oedema (DMO) using optic coherence tomography (OCT). We performed a cross-sectional observational study to validate OCT for the diagnosis of DMO using both CFT and PIF assessed by OCT (3D OCT-1 Maestro). A sample of 277 eyes from primary care diabetic patients was assessed in a Spanish region in 2014. OUTCOME: DMO diagnosed by stereoscopic mydriatic fundoscopy. OCT was used to measure CFT and PIF. A binary logistic regression model was constructed to predict the outcome using CFT and PIF. The area under the ROC curve (AUC) of the model was calculated and non-linear equations used to determine which CFT values had a high probability of the outcome (positive test), distinguishing between the presence or absence of PIF. Calculations were made of the sensitivity, specificity, and the positive (PLR) and negative (NLR) likelihood ratios. The model was validated using bootstrapping methodology. A total of 37 eyes had DMO. AUC: 0.88. Positive test: CFT ≥90 µm plus PIF (≥310 µm if no PIF). Clinical parameters: sensitivity, 0.83; specificity, 0.89; PLR, 7.34; NLR, 0.19. The parameters in the validation were similar. In conclusion, combining PIF and CFT provided a tool to very precisely discriminate the presence of DMO. Similar studies are needed to provide greater scientific evidence for the use of PIF in the diagnosis of DMO.

Validity of Optical Coherence Tomography as a Diagnostic Method for Diabetic Retinopathy and Diabetic Macular Edema.

To validate optical coherence tomography (OCT) for the diagnosis of referable retinopathy (severe, very severe or proliferative retinopathy, and macular edema) in diabetic patients. We performed a cross-sectional observational study. A random sample was analyzed comprising 136 eyes of diabetic patients referred to the hospital in Elche (Spain) with suspected referable retinopathy between October 2012 and June 2013. Primary variable: Referable retinopathy measured by ophthalmological examination of the retina. OCT data included: central foveal thickness, presence of intraretinal fluid, and fundus photographs. The receiver operating characteristic (ROC) curve was calculated to determine the minimum thickness value with a positive likelihood ratio >10. To determine the validity of OCT, the following diagnostic test was defined: Positive: if the patient had at least 1 of these criteria: foveal thickness greater than the point obtained on the previously defined ROC curve, intraretinal fluid, abnormal fundus photographs; Negative: none of the above criteria. Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and Kappa statistic were determined. Of the 136 eyes, 48 had referable retinopathy (35.3%, 95% confidence interval [CI]: 27.3-43.3). The minimum thickness value with a positive likelihood ratio >10 was 275 µm. The diagnostic test constructed showed: sensitivity, 91.67% (95% CI: 79.13-97.30); specificity, 93.18% (95% CI: 85.19-97.20); positive predictive value, 88.00% (95% CI: 75.00-95.03); negative predictive value, 95.35% (95% CI: 87.87-98.50); positive likelihood ratio, 13.44 (95% CI: 6.18-29.24); negative likelihood ratio, 0.09 (95% CI: 0.03-0.23). The Kappa value was 0.84 (95% CI: 0.75-0.94, P < 0.001. This study constructed a diagnostic test for referable diabetic retinopathy with type A evidence. Nevertheless, studies are needed to determine the validity of this test in the general diabetic population.