Association between uric acid and referable diabetic retinopathy in patients with type 2 diabetes.

Plasmatic uric acid (UA) has been inconsistently associated with diabetic retinopathy (DR). Specific sight-threatening stages of DR have not been studied for their association with UA. Cross-sectional, comparative study. Between 2014 and 2018 we recruited 210 Mexican individuals > 18 years-old with type 2 diabetes (T2D). Clinical, ophthalmological and biochemical assessment was performed with standardized funduscopic examination. Certified readers classified DR stages. The association between DR and UA was assessed by multiple logistic regression analysis, calculating odds ratios (OR) and 95% CI, after adjustment for covariates. Two hundred and ten patients were included, 41 (19.5%) had referable DR. Subjects with referable (severe or worse) DR had longer diabetes duration, 22 (15-28) vs 15 (8-20) years (P < 0.01); higher levels of UA, 6.5 (5.8-8.1) vs 5.4 (4.5-6.6) mg/dL (P < 0.01); higher systolic blood pressure, 130 (120-140) vs 120 (110-130) mmHg (P < 0.01); higher diastolic blood pressure, 78.4 ± 9.7 vs 75.4 ± 9.2 mmHg (P = 0.03); and lower glomerular filtration rate , 54.1 (41.5-69.6) vs 87.3 (66.8-108.3) mL/min/1.73m2 (P < 0.01) compared with those without referable DR. With multiple logistic regression, after adjustment, per each unit of change (mg/dL) in UA the probability of having referable DR increased 45% (OR = 1.45, 95% CI 1.12-1.87, P < 0.01). When UA was evaluated as dichotomous variable, those with levels ≥ 7.8 mg/dL had almost two times (OR = 2.81, 95% CI 1.00-7.9., P = 0.049) the probability of having referable DR compared with those with levels < 7.8 mg/dL. UA may contribute to the microvascular damage in retinal vessels and therefore hyperuricemia could be a therapeutic target to prevent DR progression.

Risk Factors Associated with Diabetic Retinopathy with and without Macular Edema in Recently Diagnosed Patients with Type 2 Diabetes.

Purpose: To evaluate the risk factors associated with diabetic macular edema (DME) in patients with a recent type 2 diabetes mellitus (T2DM) diagnosis. Patients and Methods: We conducted a case-control study at a third-level hospital in Mexico City. We enrolled patients ≥18 years old, with T2DM less than five years of diagnosis, without disabling complications, and non-smokers. The control group was patients with diabetic retinopathy and without macular edema (DR-DME). Cases were patients with DR+DME. We measured fasting glucose, creatinine, lipid profile, urinary albumin/creatinine ratio (ACR), and HbA1c. An ophthalmological examination consisted of visual acuity measurement, digital three-field fundus photography with an automatic non-mydriatic camera, slit lamp, and Optical coherence tomography (OCT) examination. Results: 183 and 61 patients with DR-DME and DR+DME, respectively, were included in the analysis. The prevalence of mild DR was higher in the DR-DME group, but the frequencies of moderate and severe retinopathy were higher in the DR+DME group. Patients in the DR-DME group had better vision than those in the DR+DME group. Logistic regression analysis revealed that age (OR, 1.07), HbA1c (OR, 1.19), and Albumin-to-Creatinine Ratio (ACR) > 30 mg/g (OR, 3.37) were associated with an increased possibility of DME compared to DR-DME. Conclusion: Our study provides insights into the association between risk factors and DME. We found a statistically strong association between HbA1c levels, age, and ACR. Patients with poor metabolic control should undergo an extensive medical examination to screen for DME, which may be related to the chronicity of DM and renal damage.

Perilipin 2-positive mononuclear phagocytes accumulate in the diabetic retina and promote PPARγ-dependent vasodegeneration.

Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia and dyslipidemia, leads to nonproliferative diabetic retinopathy (NPDR). NPDR is associated with blood-retina barrier disruption, plasma exudates, microvascular degeneration, elevated inflammatory cytokine levels, and monocyte (Mo) infiltration. Whether and how the diabetes-associated changes in plasma lipid and carbohydrate levels modify Mo differentiation remains unknown. Here, we show that mononuclear phagocytes (MPs) in areas of vascular leakage in DR donor retinas expressed perilipin 2 (PLIN2), a marker of intracellular lipid load. Strong upregulation of PLIN2 was also observed when healthy donor Mos were treated with plasma from patients with T2DM or with palmitate concentrations typical of those found in T2DM plasma, but not under high-glucose conditions. PLIN2 expression correlated with the expression of other key genes involved in lipid metabolism (ACADVL, PDK4) and the DR biomarkers ANGPTL4 and CXCL8. Mechanistically, we show that lipid-exposed MPs induced capillary degeneration in ex vivo explants that was inhibited by pharmaceutical inhibition of PPARγ signaling. Our study reveals a mechanism linking dyslipidemia-induced MP polarization to the increased inflammatory cytokine levels and microvascular degeneration that characterize NPDR. This study provides comprehensive insights into the glycemia-independent activation of Mos in T2DM and identifies MP PPARγ as a target for inhibition of lipid-activated MPs in DR.

Discapacidad visual asociada a retinopatía diabética y edema macular: un estudio de base hospitalaria / Visual impairment associated with diabetic retinopathy and macular edema: a hospital-based study

Resumen Antecedentes: Los datos sobre discapacidad visual (DV) en pacientes con diabetes son necesarios para orientar los recursos económicos y humanos que disminuyan su prevalencia. Objetivo: Estimar la prevalencia de DV relacionada con retinopatía diabética en pacientes con diabetes tipo 2 en un entorno hospitalario. Material y métodos: Estudio transversal realizado de 2014 a 2019 en una consulta externa de oftalmología. Cualquier DV se definió como agudeza visual corregida con agujero estenopeico en el ojo con mejor visión (≥ 0.24 logMAR). Se evaluó la presencia de retinopatía diabética, edema macular diabético (EMD) y cataratas. Resultados: Se incluyeron 840 pacientes; la mediana de duración de la diabetes fue de 15 años. La prevalencia de DV fue de 30 %. Se encontró retinopatía diabética en 62 % (30 % tenía retinopatía diabética que amenazaba la visión [RDAV]); 17 %, EMD y 3 %, cataratas. La razón de momios para DV moderada o de mayor gravedad fue de 9.02 para RDAV (p < 0.001), 5.89 para EMD referible (p = 0.001) y 2.51 para catarata (p = 0.006). Conclusión: Treinta por ciento de los participantes tenía algún grado de DV. La DV moderada o de mayor gravedad mostró una fuerte asociación con RDAV y EMD referible.

Abstract Background: Data on visual impairment (VI) in patients with diabetes are necessary in order to guide economic and human resources for reducing its prevalence. Objective: To estimate the prevalence of diabetic retinopathy-related VI in patients with type 2 diabetes in a hospital-based setting. Material and methods: Cross-sectional study carried out from 2014 to 2019 in an ophthalmology outpatient clinic. Any VI was defined as corrected pin-hole visual acuity in the better eye of ≥ 0.24 logMAR. The presence of diabetic retinopathy (DR), diabetic macular edema (DME) and cataract was evaluated. Results: A total of 840 patients were included; median diabetes duration was 15 years. The prevalence of VI was 30 %. DR was found in 62 % of patients (30 % had sight-threatening DR [STDR]), 17 % had referable DME, and 3 %, cataracts. The odds ratio for moderate or worse VI was 9.02 for STDR (p < 0.001), 5.89 for referable DME (p = 0.001), and 2.51 for cataract (p = 0.006). Conclusion: Thirty percent of participants had some degree of VI. Moderate or worse VI showed a strong association with STDR and referable DME.

Prevalence and associated risk factors of diabetic retinopathy and macular oedema in patients recently diagnosed with type 2 diabetes.

OBJECTIVE: To determine the prevalence of diabetic retinopathy (DR) and diabetic macular oedema (DME) and their associated risk factors in patients recently diagnosed with type 2 diabetes. METHODS AND ANALYSIS: We carried out a cross-sectional study from April 2014 to August 2017. We included patients aged ≥18 years. Diabetes was defined as fasting plasma glucose of >7.8 mmol/L or 2-hour postload plasma glucose of >11.1 mmol/L. Non-mydriatic fundus examination with a digital-fundus camera was performed. Three images centred in the macula, optic disc and temporal to the macula were obtained and graded according to the Scottish Scale Classification of Diabetic Retinopathy. RESULTS: 1232 patients (mean age 51.5 years) with a diabetes duration of 0-5 years were examined. Age-adjusted and sex-adjusted prevalence of DR and DME was 17.4% (95% CI 15.3% to 19.6%) and 6.6% (95% CI 5.4% to 8.2%), respectively. DR was associated with diabetes duration (OR per year=1.20, p<0.001), haemoglobin A1c (HbA1c) from 7.0 to 8.9 (OR=2.19, p<0.001), HbA1c≥9 (OR=2.98, p<0.001) and systolic blood pressure (SBP) (OR=1.16 per 5 mm Hg, p<0.001). DME was associated with diabetes duration (OR per year=1.26, p<0.01), HbA1c from 7.0 to 8.9 (OR=2.26, p<0.05), HbA1c≥9 (OR=2.38, p<0.01), SBP (OR per mm Hg=1.15, p<0.001) and albuminuria (OR=2.45, p<0.01). CONCLUSION: Our study contributes to the evidence of progressive increase in DR and DME risk in early stages of diabetes, supporting the urgent need for early screening.

PARACENTRAL ACUTE MIDDLE MACULOPATHY IN PURTSCHER RETINOPATHY.

PURPOSE: To describe paracentral acute middle maculopathy associated with Purtscher retinopathy, particularly in Purtscher flecken lesions as a retinal complication in a case secondary to fractures of long bones. METHODS: Case report. RESULTS: A 16-year-old boy with bilateral paracentral scotomata presented with bilateral paracentral acute middle maculopathy as part of Purtscher retinopathy in both eyes as consequence of tibia and fibula fractures. CONCLUSION: Paracentral acute middle maculopathy is one of the optical coherence tomography findings in Purtscher retinopathy.

CHEMOTHERAPEUTIC NADIR-ASSOCIATED RETINOPATHY.

PURPOSE: To describe subinternal limiting membrane hemorrhage as a retinal complication of chemotherapy nadir in a patient with leukemia. METHODS: Case report. RESULTS: A 23-year-old man presented with bilateral subinternal limiting membrane hemorrhages in both eyes as a manifestation of thrombocytopenia secondary to chemotherapy treatment for acute myeloid leukemia. CONCLUSION: Chemotherapeutic nadir-associated retinopathy may present with sub-internal limiting membrane hemorrhages most probably secondary to thrombocytopenia.

MULTICOLOR SCANNING LASER IMAGING IN LIPEMIA RETINALIS.

PURPOSE: To describe multicolor scanning laser imaging (MSLI) and conventional fundus photography findings in lipemia retinalis (LR). METHODS: We report two LR cases. The first case is a 47-year-old diabetic woman with LR secondary to familial hypertriglyceridemia examined with MSLI, conventional fundus photography, and optical coherence tomography (OCT). The second case is a 39-year-old diabetic man with hypertriglyceridemia and LR. He was followed over time with conventional fundus photography of his retina until metabolic control was achieved. RESULTS: In the first case, MSLI showed retinal arteries with an intense yellow and retinal veins with a pale yellow color. Fundus photography disclosed only mild pale red vessels. Optical coherence tomography detected macular edema and hyperreflective changes of retinal vessels. In the second case, fundus photography showed vessels with a pale red appearance that normalized after metabolic control of triglycerides. CONCLUSION: We described the retinal findings in patients with LR using different image modalities. Specifically, we report the findings with MSLI not previously described. While regular fundus photography may show mild changes in LR, the MSLI modality may show more significant findings assisting in the diagnosis and follow-up of this disease.

Congenital hereditary endothelial dystrophy caused by SLC4A11 mutations progresses to Harboyan syndrome.

PURPOSE: Homozygous mutations in SLC4A11 cause 2 rare recessive conditions: congenital hereditary endothelial dystrophy (CHED), affecting the cornea alone, and Harboyan syndrome consisting of corneal dystrophy and sensorineural hearing loss. In addition, adult-onset Fuchs endothelial corneal dystrophy (FECD) is associated with dominant mutations in SLC4A11. In this report, we investigate whether patients with CHED go on to develop hearing loss and whether their parents, who are carriers of an SLC4A11 mutation, show signs of having FECD. METHODS: Patients with CHED were screened for mutations in the SLC4A11 gene and underwent audiometric testing. The patients and their parents underwent a clinical examination and specular microscopy. RESULTS: Molecular analyses confirmed SLC4A11 mutations in 4 affected individuals from 3 families. All the patients were found to have varying degrees of sensorineural hearing loss at a higher frequency range. Guttate lesions were seen in 2 of the 4 parents who were available for examination. CONCLUSIONS: Our observations suggest that CHED caused by homozygous SLC4A11 mutations progresses to Harboyan syndrome, but the severity of this may vary considerably. Patients with CHED should therefore be monitored for progressive hearing loss. We could not determine conclusively whether the parents of the patients with CHED were at increased risk of developing late-onset FECD.

Rhodopsin p.N78I dominant mutation causing sectorial retinitis pigmentosa in a pedigree with intrafamilial clinical heterogeneity.

OBJECTIVE: The purpose of this study was to determine the molecular basis of retinitis pigmentosa (RP) in a 4 affected sib-family segregating this retinal phenotype. METHODS: Affected sibs underwent complete ophthalmologic examination including funduscopic inspection, electroretinogram, fluorescein angiography, visual field measurement, and optical coherence tomography. Both parents were deceased after their sixties and were reported with no visual handicap. Molecular analysis included direct nucleotide sequencing of the rhodopsin gene (RHO), at chromosome 3q21-q24, in DNA from a total of 4 affected sibs. A total of 200 ethnically matched alleles were included as mutation controls. RESULTS: Sector RP was clinically documented in this family. Wide phenotypic variability was observed with visual acuities ranging from 20/20 to 20/200 and variable funduscopic appearance. Molecular analysis disclosed a c.233A>T mutation at RHO exon 1, predicting a missense p.N78I substitution. CONCLUSIONS: Even though RP can be caused by mutations in a variety of genes, the RHO gene was chosen to be investigated in this RP family since it has been previously associated to sector disease. This case exemplifies the value of guiding RP molecular analysis based on funduscopic features.