Changes in the Epidemiology of Diabetic Retinopathy in Spain: A Systematic Review and Meta-Analysis.

BACKGROUND: The aim of the present study was to determine the prevalence and incidence of diabetic retinopathy (DR) and its changes in the last 20 years in type 2 diabetes mellitus (T2DM) patients in Spain. METHODS: A systematic review with a meta-analysis was carried out on the studies published between 2001-2020 on the prevalence and incidence of DR and sight-threatening diabetic retinopathy (STDR) in Spain. The articles included were selected from four databases and publications of the Spanish Ministry of Health and Regional Health Care System (RHCS). The meta-analysis to determine heterogeneity and bias between studies was carried out with the MetaXL 4.0. RESULTS: Since 2001, we have observed an increase in the detection of patients with DM, and at the same time, screening programs for RD have been launched; thus, we can deduce that the increase in the detection of patients with DM, many of them in the initial phases, far exceeds the increased detection of patients with DR. The prevalence of DR was higher between 2001 and 2008 with values of 28.85%. These values decreased over the following period between 2009 and 2020 with a mean of 15.28%. Similarly the STDR prevalence decrease from 3.67% to 1.92% after 2008. The analysis of the longitudinal studies determined that the annual DR incidence was 3.83%, and the STDR annual incidence was 0.41%. CONCLUSION: In Spain, for T2DM, the current prevalence of DR is 15.28% and 1.92% forSTDR. The annual incidence of DR is 3.83% and is 0.41% for STDR.

A Screening Tool for Self-Evaluation of Risk for Age-Related Macular Degeneration: Validation in a Spanish Population.

Purpose: The objectives of this study were the creation and validation of a screening tool for age-related macular degeneration (AMD) for routine assessment by primary care physicians, ophthalmologists, other healthcare professionals, and the general population. Methods: A simple, self-administered questionnaire (Simplified Théa AMD Risk-Assessment Scale [STARS] version 4.0) which included well-established risk factors for AMD, such as family history, smoking, and dietary factors, was administered to patients during ophthalmology visits. A fundus examination was performed to determine presence of large soft drusen, pigmentary abnormalities, or late AMD. Based on data from the questionnaire and the clinical examination, predictive models were developed to estimate probability of the Age-Related Eye Disease Study (AREDS) score (categorized as low risk/high risk). The models were evaluated by area under the receiving operating characteristic curve analysis. Results: A total of 3854 subjects completed the questionnaire and underwent a fundus examination. Early/intermediate and late AMD were detected in 15.9% and 23.8% of the patients, respectively. A predictive model was developed with training, validation, and test datasets. The model in the test set had an area under the curve of 0.745 (95% confidence interval [CI] = 0.705-0.784), a positive predictive value of 0.500 (95% CI = 0.449-0.557), and a negative predictive value of 0.810 (95% CI = 0.770-0.844). Conclusions: The STARS questionnaire version 4.0 and the model identify patients at high risk of developing late AMD. Translational Relevance: The screening instrument described could be useful to evaluate the risk of late AMD in patients >55 years without having an eye examination, which could lead to more timely referrals and encourage lifestyle changes.

Rho-Kinase Inhibitors for the Treatment of Refractory Diabetic Macular Oedema.

Diabetic macular oedema (DMO) is one of the leading causes of vision loss associated with diabetic retinopathy (DR). New insights in managing this condition have changed the paradigm in its treatment, with intravitreal injections of antivascular endothelial growth factor (anti-VEGF) having become the standard therapy for DMO worldwide. However, there is no single standard therapy for all patients DMO refractory to anti-VEGF treatment; thus, further investigation is still needed. The key obstacles in developing suitable therapeutics for refractory DMO lie in its complex pathophysiology; therefore, there is an opportunity for further improvements in the progress and applications of new drugs. Previous studies have indicated that Rho-associated kinase (Rho-kinase/ROCK) is an essential molecule in the pathogenesis of DMO. This is why the Rho/ROCK signalling pathway has been proposed as a possible target for new treatments. The present review focuses on the recent progress on the possible role of ROCK and its therapeutic potential in DMO. A systematic literature search was performed, covering the years 1991 to 2021, using the following keywords: "rho-Associated Kinas-es", "Diabetic Retinopathy", "Macular Edema", "Ripasudil", "Fasudil" and "Netarsudil". Better insight into the pathological role of Rho-kinase/ROCK may lead to the development of new strategies for refractory DMO treatment and prevention.

Signature of Circulating Biomarkers in Recurrent Non-Infectious Anterior Uveitis. Immunomodulatory Effects of DHA-Triglyceride. A Pilot Study.

The purpose of this study was to identify circulating biomarkers of recurrent non-infectious anterior uveitis (NIAU), and to address the anti-inflammatory effects of triglyceride containing docosahexaenoic acid (DHA-TG). A prospective multicenter study was conducted in 72 participants distributed into: patients diagnosed with recurrent NIAU in the quiescence stage (uveitis group (UG); n = 36) and healthy controls (control group (CG); n = 36). Each group was randomly assigned to the oral supplementation of one pill/day (+) containing DHA-TG (n = 18) or no-pill condition (-) (n = 17) for three consecutive months. Data from demographics, risk factors, comorbidities, eye complications and therapy were recorded. Blood was collected and processed to determine pro-inflammatory biomarkers by bead-base multiplex assay. Statistical processing with multivariate statistical analysis was performed. The mean age was 50, 12 (10, 31) years. The distribution by gender was 45% males and 55% females. The mean number of uveitis episodes was 5 (2). Higher plasma expression of interleukin (IL)-6 was detected in the UG versus the CG (p = 5 × 10-5). Likewise, significantly higher plasma levels were seen for IL-1ß, IL-2, INFγ (p = 10-4), and TNFα (p = 2 × 10-4) in the UG versus the CG. Significantly lower values of the above molecules were found in the +DHA-TG than in the -DHA-TG subgroups, after 3 months of follow-up, TNFα (p = 10-7) and IL-6 (p = 3 × 10-6) being those that most significantly changed. Signatures of circulating inflammatory mediators were obtained in the quiescent stage of recurrent NIAU patients. This 3-month follow-up strongly reinforces that a regular oral administration of DHA-TG reduces the inflammatory load and may potentially supply a prophylaxis-adjunctive mediator for patients at risk of uveitis vision loss.

Interpretation of OCT and OCTA images from a histological approach: Clinical and experimental implications.

Optical coherence tomography (OCT) and OCT angiography (OCTA) have been a technological breakthrough in the diagnosis, treatment, and follow-up of many retinal diseases, thanks to its resolution and its ability to inform of the retinal state in seconds, which gives relevant information about retinal degeneration. In this review, we present an immunohistochemical description of the human and mice retina and we correlate it with the OCT bands in health and pathological conditions. Here, we propose an interpretation of the four outer hyperreflective OCT bands with a correspondence to retinal histology: the first and innermost band as the external limiting membrane (ELM), the second band as the cone ellipsoid zone (EZ), the third band as the outer segment tips phagocytosed by the pigment epithelium (PhaZ), and the fourth band as the mitochondria in the basal portion of the RPE (RPEmitZ). The integrity of these bands would reflect the health of photoreceptors and retinal pigment epithelium. Moreover, we describe how the vascular plexuses vary in different regions of the healthy human and mice retina, using OCTA and immunohistochemistry. In humans, four, three, two or one plexuses can be observed depending on the distance from the fovea. Also, specific structures such as vascular loops in the intermediate capillary plexus, or spider-like structures of interconnected capillaries in the deep capillary plexus are found. In mice, three vascular plexuses occupy the whole retina, except in the most peripheral retina where only two plexuses are found. These morphological issues should be considered when assessing a pathology, as some retinal diseases are associated with structural changes in blood vessels. Therefore, the analysis of OCT bands and OCTA vascular plexuses may be complementary for the diagnosis and prognosis of retinal degenerative processes, useful to assess therapeutic approaches, and it is usually correlated to visual acuity.

Intravitreal dexamethasone implants for diabetic macular edema.

AIM: To evaluate the safety and efficacy of a dexamethasone (DEX) intravitreal implant for diabetic macular edema (DME). METHODS: Totally 113 eyes of 84 patients were divided in three subgroups: naive patients (n=11), pseudophakic patients (n=72) and phakic patients (n=30). Inclusive criterion comprised adult diabetic patients with central fovea thickening and impaired visual acuity resulting from DME for whom previous standard treatments showed no improvement in both central macular thickness (CMT) and best corrected visual acuity (BCVA) after at least 3mo of treatment. Outcome data were obtained from patient visits at baseline and at months 1, 3, 5, 9 and 12 after the first DEX implant injection. At each of these visits, patients underwent measurement of BCVA, a complete eye examination and measurement of CMT and macular volume (MV) carried out with optical coherence tomography (OCT) images. RESULTS: Seventy-three eyes (64.5%) received a single implant, 30 (26.5%) received two implants and 10 (9%) received three implants. At baseline, average in BCVA, CMT and MV were 43.5±20.8, 462.8±145 and 12.6±2.5 respectively. These values improved significantly at 1mo (BCVA: 47.2±19.5, CMT: 339.6±120, MV: 11.11±1.4) and 3mo (BCVA: 53.2±18.1, CMT: 353.8±141, MV: 11.3±1.3) (P≤0.05). At 5mo (BCVA: 50.9±19.8, CMT: 425±150, MV: 12.27±2.3), 9mo (BCVA: 48.4±17.6, CMT: 445.5±170, MV: 12.5±2.3) and 12mo (BCVA: 47.7±18.8, CMT: 413.2±149, MV: 12.03±2.5), improvements in the three parameters were no longer statistically significant and decreased progressively but did not reach baseline values. There were no clinical differences between subgroups. Ocular complications were minimal. CONCLUSION: Patients with DEX implants show maximum efficacy at 3mo which then declined progressively, but is still better than baseline values at the end of follow-up.

Diabetic Macular Edema Pathophysiology: Vasogenic versus Inflammatory.

Diabetic macular edema (DME) can cause blindness in diabetic patients suffering from diabetic retinopathy (DR). DM parameters controls (glycemia, arterial tension, and lipids) are the gold standard for preventing DR and DME. Although the vascular endothelial growth factor (VEGF) is known to play a role in the development of DME, the pathological processes leading to the onset of this disease are highly complex and the exact sequence in which they occur is still not completely understood. Angiogenesis and inflammation have been shown to be involved in the pathogenesis of this disease. However, it still remains to be clarified whether angiogenesis following VEGF overexpression is a cause or a consequence of inflammation. This paper provides a review of the data currently available, focusing on VEGF, angiogenesis, and inflammation. Our analysis suggests that angiogenesis and inflammation act interdependently during the development of DME. Knowledge of DME etiology seems to be important in treatments with anti-VEGF or anti-inflammatory drugs. Current diagnostic techniques do not permit us to differentiate between both etiologies. In the future, diagnosing the physiopathology of each patient with DME will help us to select the most effective drug.