Retinal Ciliopathy in the Patient with Transplanted Kidney: Case Report.

A review of a rare case of a proven mutation in the RP1 gene (RP1c.2029C>T, p. (ARG677*) in a kidney transplant patient was presented herein. According to his medical history, he had tonsillectomy performed at the age of 20 due to erythrocyturia, and at the age of 32 he was treated for malignant hypertension. The patient had been diagnosed with chronic renal failure at age 56 years. During an eye examination in 2016, retinitis pigmentosa was suspected and the patient was advised to run further tests. After an ophthalmological examination and tests, genetic testing was performed and a mutation in the RP1 gene encoding a family of proteins which are components of microtubules in photoreceptor primary cilia was proven. The literature search found that mutations in the RP1 gene have so far been exclusively associated with a non-syndromic form of retinal degeneration. However, the RP1 protein is expressed in the kidneys, and it remains unclear why the mutation of this gene so far was only specifically related to retinal photoreceptor function and not to arterial hypertension and renal disease. Primary cilia are thought to act as potential mechanosensory fluid-flow receptors in the vascular endothelium and kidney and their dysfunction results in atherosclerotic changes, hypertension, and chronic renal failure.

N-Glycosylation Patterns across the Age-Related Macular Degeneration Spectrum.

The pathogenesis of age-related macular degeneration (AMD) remains elusive, despite numerous research studies. Therefore, we aimed to investigate the changes of plasma and IgG-specific N-glycosylation across the disease severity spectrum. We examined 2835 subjects from the 10.001 Dalmatians project, originating from the isolated Croatian islands of Vis and Korcula. All subjects were classified into four groups, namely (i) bilateral AMD, (ii) unilateral AMD, (iii) early-onset drusen, and (iv) controls. We analysed plasma and IgG N-glycans measured by HPLC and their association with retinal fundus photographs. There were 106 (3.7%) detected cases of AMD; 66 of them were bilateral. In addition, 45 (0.9%) subjects were recorded as having early-onset retinal drusen. We detected several interesting differences across the analysed groups, suggesting that N-glycans can be used as a biomarker for AMD. Multivariate analysis suggested a significant decrease in the immunomodulatory bi-antennary glycan structures in unilateral AMD (adjusted odds ratio 0.43 (95% confidence interval 0.22-0.79)). We also detected a substantial increase in the pro-inflammatory tetra-antennary plasma glycans in bilateral AMD (7.90 (2.94-20.95)). Notably, some of these associations were not identified in the aggregated analysis, where all three disease stages were collapsed into a single category, suggesting the need for better-refined phenotypes and the use of disease severity stages in the analysis of more complex diseases. Age-related macular degeneration progression is characterised by the complex interplay of various mechanisms, some of which can be detected by measuring plasma and IgG N-glycans. As opposed to a simple case-control study, more advanced and refined study designs are needed to understand the pathogenesis of complex diseases.

Searching for carbonylome biomarkers of aging - development and validation of the proteomic method for quantification of carbonylated protein in human plasma.

AIM: To develop a method for measuring protein carbonylation in human plasma and serum samples, which was previously implied in numerous age-related phenotypes. METHODS: Protein expression and carbonylation were analyzed in plasma samples obtained from 12 healthy human individuals by using a novel method that combines affinity-based albumin and immunoglobulin G removal, and aminooxy dyeing in one- or two-dimensional gels. In addition, carbonylome profile of plasma and serum was compared. Coefficients of variation and intra-class correlation coefficients were used in statistical analysis. RESULTS: Following a step-wise laboratory development and optimization process, we measured the protein expression and carbonylation for 813 proteins from the plasma. The analysis of repeated measurements suggested excellent coefficients of variation, which rarely exceeded 10%. The average value of intra-class correlation based on absolute agreement (ICC) for protein expression was 0.97±0.02, while for carbonylation it was 0.73±0.24. The removal of the most extreme protein outlier in carbonylation assessment increased the average ICC to 0.87±0.04. Low protein spot volume substantially reduced repeatability. Serum carbonylation estimates were similar to those from plasma, with the ICC in the range of 0.86-0.89. CONCLUSION: We developed a reliable method for the measurement of human plasma protein carbonylation, which can be used for the assessment of carbonylome biomarkers of aging.

Paramacular Choriocapillaris Atrophy.

In this paper, a review of a rare case of paramacular choriocapillaris atrophy with a foveal-sparing phenotype is carried out. The 73-year-old patient stated that they had impaired vision and photophobia in both eyes during a regular ophthalmological examination, denying visual field defects and night blindness. A complete ophthalmological examination (best-corrected visual acuity, applanation tonometry, and biomicroscopy of anterior and posterior segments) and diagnostic tests, including fundus autofluorescence, fluorescein angiography, optical coherence tomography with angiography, computerized perimetry, and electroretinography, were carried out. The underlying genetic pattern is unclear, which points to paramacular choriocapillaris atrophy. According to recent research on histology, pathologies categorized as regional choroidal dystrophies are caused by alterations at the level of the retinal pigment epithelium. Despite the unresolved etiopathogenetic mechanism of foveal sparing in central choroidal and retinal dystrophies, a highly variable disease phenotype with spared fovea and central visual acuity present in a variety of heterogeneous dystrophies supports a disease-independent mechanism that allows the survival of foveal cones. The related preservation of BCVA has implications for individual prognosis and influences how treatment trials for choroidal and retinal dystrophies are designed.

Genetic Background of a Recurrent Unusual Combined Form of Retinal Vein Occlusion: A Case Report.

The authors report a rare case of nonischemic branch retinal vein occlusion and nonischemic hemiretinal vein occlusion in a patient with impaired fibrinolysis. A 61-year-old woman presented to the Department of Ophthalmology, Clinical Hospital Center Split, Croatia, with acute blurring of vision in the right eye (RE) due to branch retinal vein occlusion. Ophthalmologic evaluation revealed a best corrected visual acuity (BCVA) of 0.02 in the RE and of 1.0 in the left eye. Ophthalmoscopy and fluorescein angiography of the RE demonstrated signs of nonischemic branch retinal vein occlusion. She was otherwise healthy and had no other ocular and systemic diseases. She was treated with 3 consecutive intravitreal applications of anti-vascular endothelial growth factor (anti-VEGF; bevacizumab) due to cystoid macular edema with full resolution of the intraretinal fluid and improvement of the BCVA to 0.9. After 8 months, she presented again with acute blurring of vision in the same (right) eye with a BCVA of 0.5. Ophthalmoscopy and fluorescein angiography of the RE indicated nonischemic hemiretinal vein occlusion. She was treated with a single intravitreal application of anti-VEGF (ranibizumab) due to macular edema. Full resolution of the intraretinal fluid and improvement of the BCVA to 0.9 were achieved. A laboratory workup was performed to rule out all known causes of retinal venous occlusive disease, which showed negative results. A molecular analysis showed the gen of thrombophilia - plasminogen activator inhibitor (PAI)-1 4G/5G polymorphism genotype - as the only risk factor for retinal venous occlusive disease in our patient.

Epidemiology of ocular trauma in children requiring hospital admission: a 16-year retrospective cohort study.

BACKGROUND: To study the epidemiology of ocular trauma requiring hospital admission in children under 18 years in age. METHODS: This retrospective cohort study included pediatric patients with ocular injuries at the Ophthalmology Department of the Clinical Hospital Centre, Split, Croatia, from 2000 to 2015, classified according to the Birmingham Eye Trauma Terminology. RESULTS: There were 353 children hospitalized, 82% of boys (mean age 11 years) and 18% of girls (mean age 10 years). The majority of traumas occurred in the outside environment (70%, n = 249), followed by occurrences at home (17%, n = 60), and at a school/nursery (8%, n = 28). Final visual acuity was 6/18 or better in 286 (96%) patients with closed globe injury and in 26 (49%) patients with open globe injury. Severe impairment of vision was found in 12 (4.4%) patients in the closed globe injury group and 26 (49%) patients in the open globe injury group. A statistically significant difference was found between final visual acuity and initial visual acuity in all patients (χ2 = 12.8; P < 0.001). CONCLUSION: The majority of pediatric eye injuries are happening in the outside environment and are preventable. Implementation of well-established safety precautions would greatly reduce this source of visual disability in children.

Left ventricular systolic function in selected type 1 diabetic patients with or without diabetic retinopathy and microalbuminuria.

Vascular endothelial dysfunction is a basic etiologic factor for the development of late clinical complications in patients with diabetes mellitus type 1, such as diabetic retinopathy, diabetic nephropathy (which is characterized at the very beginning by microalbuminuria), and left ventricular cardiac dysfunction. The aims of this study were to determine the prevalence of asymptomatic left ventricular systolic dysfunction in patients with diabetes mellitus type 1 and with or without diabetic retinopathy and microalbuminuria, and to correlate the duration of diabetes with the dynamics of diabetic retinopathy, microalbuminuria and asymptomatic left ventricular dysfunction development in these patients. One-hundred and twenty selected patients with diabetes mellitus type 1 were examined by ophthalmologist and cardiologist. All patients underwent ergometric testing and two-dimensional (2-D) echocardiography with pulsed Doppler. Patients were divided into three groups according to their fundus findings and microalbuminuria: (1) patients without diabetic retinopathy and without microalbuminuria (n = 40); (2) patients with diabetic retinopathy without microalbuminuria (n = 40); and (3) patients with diabetic retinopathy and microalbuminuria (n = 40). All three groups of patients with diabetes mellitus type 1 (with low cardiovascular risk, regulated blood sugar, and without diabetic neuropathy) had echocardiographic values in the normal range. We found no statistically significant correlation between the duration of diabetes mellitus type 1 and echocardiographic values.