Neurofibromatosis Type 1-Retinal Alterations Detectable with Optical Coherence Tomography Angiography.

Neurofibromatosis type 1 (NF 1) is a multisystemic genetic disorder involving aberrant proliferation of multiple tissues of a neural crest origin. It represents a tumor predisposition syndrome characterized by a wide range of clinical manifestations, such as benign tumors, which primarily affect the skin and the nervous system. The most frequent clinical signs of NF 1 include café-au-lait spots all over the surface of the skin and axillary freckling; however, these signs can be accompanied by more severe manifestations such as the growth of both benign and malignant nervous system tumors and skeletal dysplasia, as well as a wide range of ocular manifestations. We report the rare case of retinal microvascular alterations and choroidal nodules in a 15 year old male patient with NF 1, detectable on optical coherence tomography angiography (OCTA). The hyperreflective choroidal nodules modified the profile of the choroidal vasculature. The retinal microvascular alterations in the form of clustered capillaries were detected in the superficial capillary plexus located nasally to the macular region. Retinal vascular abnormalities undetectable on fundus photography or fundoscopy can be present in patients with NF 1. Indirect ophthalmoscopy of our study patient was unremarkable. However, retinal vascular abnormalities were seen on OCTA scans in the superficial capillary plexus and choroidal nodules were detected on raster OCT scans. OCTA represents a useful imaging technique for detecting retinal microvascular abnormalities, which can be considered additional distinctive signs of NF 1.

Chitosan Versus Dapagliflozin in a Diabetic Cardiomyopathy Mouse Model.

Diabetes mellitus is a metabolic disorder with global economic implications that can lead to complications such as diabetic cardiomyopathy. The aim of this study was to compare the effects of chitosan versus dapagliflozin in mouse diabetic cardiomyopathy. We used 32 C57Bl/6 male mice aged between 8 and 10 weeks, which were randomly divided into Control-without diabetes mellitus (DM), type 1 DM (T1DM), T1DM + Chitosan, and T1DM + Dapapgliflozin groups. We induced diabetes with streptozotocin and treated the animals for 12 weeks. The analysis showed a reduction in intramyocardial fibrosis in the T1DM + Dapapgliflozin compared to T1DM animals. In T1DM + CHIT, a reduction in intramyocardial fibrosis was observed although, accordingly, there was also no significant decrease in blood glucose. The level of oxidative stress was reduced in the groups of treated animals compared to T1DM. All these observed changes in the structure and function of hearts were highlighted in the echocardiographic examination. In the treated groups, there was delayed appearance of left ventricular (LV) hypertrophy, a slight decrease in the ejection fraction of the LV, and an improved diastolic profile. The results demonstrate that chitosan has promising effects on diabetic cardiomyopathy that are comparable to the beneficial effects of dapagliflozin.

Correlations between Retinal Microvascular Parameters and Clinical Parameters in Young Patients with Type 1 Diabetes Mellitus: An Optical Coherence Tomography Angiography Study.

OBJECTIVES: In the current study, we investigated the correlations between retinal microvascular parameters using optical coherence tomography angiography (OCTA) and clinical parameters for a group of 69 young patients with type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: This retrospective, exploratory study enrolled 69 patients between 5 years old and 30 years old who met the inclusion criteria. All the study participants underwent a comprehensive ophthalmic examination and OCTA scans for the evaluation of the retinal microcirculation. The retinal OCTA parameters were correlated with the following clinical parameters: the patient's age at the onset of the disease, the duration of T1DM, the BMI at the time of enrollment in the study, the HbA1C values at onset, the mean values of HbA1C over the period of monitoring the disease and the degree of DKA at onset. RESULTS: For the study group, the foveal avascular zone (FAZ) area and perimeter correlated positively with the mean value of HbA1C (Pearson correlation, Sig.2-Tailed Area: 0.044; perimeter: 0.049). The total vessel density in the superficial capillary plexus (SCP) correlated negatively with the duration of T1DM, based on the superior and inferior analyzed areas (Spearman correlation, Sig.2-Tailed SCP in total region: 0.002; SCP in the superior region: 0.024; SCP in the inferior region: 0.050). The foveal thickness also correlated negatively with the levels of diabetic ketoacidosis (DKA) at onset (Spearman correlation, Sig.2-Tailed: 0.034) and the levels of HbA1C at onset (Spearman correlation, Sig.2-Tailed: 0.047). Further on, the study patients were distributed into two groups according to the duration of the disease: group 1 included 32 patients with a duration of T1DM of less than 5 years, and group 2 included 37 patients with a duration of T1DM of more than 5 years. Independent t-tests were used to compare the OCTA retinal parameters for the two subgroups. While the FAZ-related parameters did not show significant statistical differences between the two groups, the vessel densities in both the SCP and DCP were significantly lower in group 2. CONCLUSIONS: Our data suggest that specific alterations in OCTA imaging biomarkers correlate with various clinical parameters: the FAZ area and perimeter increase with higher mean values of HbA1C, leading to poor metabolic control. Moreover, the SCP total vessel density decreases as the duration of T1DM increases. Regarding the vessel densities in the SCP and the DCP, they decrease with a duration of the disease of more than 5 years.

Retinal Microvascular Alterations in a Patient with Type 1 Diabetes Mellitus, Hemoglobin D Hemoglobinopathy, and High Myopia-Case Report and Review of the Literature.

Type 1 diabetes mellitus (type 1 DM) is one of the most prevalent endocrinological diseases among children and young adults, with a growing incidence rate reaching up to 2.9 new cases per year per 100,000 persons below 15 years of age. We report a rare case of a 20-year-old female patient with type 1 DM, hemoglobin D (HbD) heterozygote variant and high myopia of -10.00 spheric diopters, and describe the retinal microvascular alterations visible on OCT angiography (angio-OCT). The patient also presented with a severe stature deficit (less than three standard deviations) and delayed puberty, which could not be explained only by suboptimal glycemic control and indicated possible hypopituitarism. HbA1c level evaluated with the high-performance liquid chromatography (HPLC) method was 6.5%, a falsely low value due to HbD hemoglobinopathy. On ophthalmic evaluation, the angio-OCT scan showed the following retinal microvascular alterations in the right eye (RE): the FAZ (Foveal Avascular Zone) area was 0.39 mm2, the FAZ perimeter was 2.88 mm, and the circularity index was 0.58. The following alterations were shown in the left eye (LE): the FAZ area was 0.34 mm2, the FAZ perimeter was 3.21 mm, and the circularity index was 0.41. Clinicians should consider high-performance retinal screening methods such as angio-OCT evaluation for young type 1 DM patients, especially for those with associated pathologies like high myopia and hemoglobinopathies. Moreover, multiple evaluation methods of HbA1c values are mandatory as hemoglobinopathies can interfere with the accuracy of HbA1c assay methods.

Early Retinal Microvascular Alterations in Young Type 1 Diabetic Patients without Clinical Retinopathy.

The purpose of this study is to identify and quantify preclinical changes with the help of optical coherence tomography angiography (OCTA) within the retinal microcirculation of young type 1 diabetes (T1D) patients without clinical signs of diabetic retinopathy (DR) and to compare these results with those obtained from healthy age-matched subjects. OCTA is currently used for monitoring diabetic retinopathy; however, there is no current consensus on which OCTA parameter alterations predict the first clinical signs of diabetic retinopathy. The main challenge that young patients with T1D face during the course of the disease is that they can rapidly progress to the development of DR, especially during adolescence. Moreover, they also present an increased risk of rapid progression toward advanced stages of DR and vision loss compared to type 2 diabetes patients, indicating the importance of early diagnosis and intervention. The limitations of the currently used screening procedures that led to the conceptualization of our study are the difficulties in performing fluorescein angiography tests for diagnosing the clinical signs of DR on young patients, namely the invasive procedure of dye injection, the risk of allergic reactions and the long duration of the examination. Moreover, given the long life expectancy of young T1D patients, it is essential to identify the preclinical changes in retinal microvasculature before reaching the first clinical signs quantifiable by FFA. The clinical study enrolled 119 subjects aged between 4 and 30 years old with a mean age of 13 years old, comprising 61 T1D patients with a mean duration of the disease of 4 years and 8 months and 58 healthy age-matched subjects for the control group. OCTA scans were performed using the RevoNX 130 OCTA device (Optopol) to evaluate the following retinal parameters: foveal avascular zone (FAZ) area, perimeter and circularity, overall foveal thickness, and superficial and deep vessel densities. Statistically significant differences between the two groups were identified for the following parameters: the FAZ area in the T1D group (0.42 ± 0.17) was larger than the control group (0.26 ± 0.080), the FAZ circularity (0.41 ± 0.11) was decreased compared to the control group (0.61 ± 0.08) and the FAZ perimeter was larger (3.63 ± 0.97) compared to the control group (2.30 ± 0.50). The overall foveal thickness was decreased in the T1D group (222.98 ± 17.33) compared to the control group (230.64 ± 20.82). The total vessel density of the superficial capillary plexus (SCP) on an investigated area of 6 X 6 mm centered around the fovea was decreased in the T1D group (37.4164 ± 2.14) compared to the control group (38.0241 ± 2.44). Our data suggest that specific imaging biomarkers such as FAZ perimeter, area and circularity, decreased overall foveal thickness and decreased vessel density in the SCP precede the clinical diagnosis of DR in young T1D patients and represent useful parameters in quantifying capillary nonperfusion in T1D patients without clinical signs of DR.

Retinal Functional Impairment in Diabetic Retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is a neurodegenerative disease of the retina. The aim of our study was to analyze latency changes in a full-field electroretinogram (ERG) in patients with type 2 diabetes. MATERIAL: This prospective study included 15 diabetic patients without DR, 16 diabetic patients with non-proliferative DR, 14 patients with pre-proliferative DR, 15 patients with proliferative DR, and 14 age-matched controls. All the participants underwent ophthalmologic examination and full-field ERGs. The ERGs were recorded with the Metrovision MonPackOne system. The latencies were analyzed for "a"- and "b"-waves in the dark-adapted (DA) 0.01 ERG, DA 3.0 ERG, DA oscillatory potentials, light-adapted (LA) 3.0 ERG, and 30 Hz flicker ERG. RESULTS: The delayed responses of healthy subjects compared to diabetic patients without DR were the DA oscillatory potentials (25.45 ± 1.04 ms vs. 26.15 ± 0.96 ms, p = 0.027). When comparing diabetic patients without DR and with non-proliferative DR, we did not obtain statistically significant delays. Significant delays in the DA 0.01 "b"-wave (61.91 ± 5.52 ms vs. 66.36 ± 8.12 ms, p = 0.029), DA 3.0 "b"-wave (41.01 ± 2.50 ms vs. 44.16 ± 3.78 ms, p = 0.035), and LA 3.0 "a"-wave (16.21 ± 0.91 ms vs. 16.99 ± 1.16 ms, p = 0.045) were found between non-proliferative DR and pre-proliferative DR. When comparing the groups of patients with pre-proliferative DR and proliferative DR, the LA 3.0 ERG "b"-wave (32. 63 ± 2.53 ms vs. 36.19 ± 3.21 ms, p < 0.0001), LA 30 Hz flicker ERG "a"-wave (19.56 ± 3.59 vs. 21.75 ± 4.74 ms, p= 0.025), and "b"-wave (32.23 ± 4.02 vs. 36.68 ± 3.48 ms, p = 0.017) were delayed. CONCLUSIONS: the electrophysiological findings from our study indicate that there is a substantial dysfunction of the neural retina in all stages of DR.

Retinal morphological and functional response to Idebenone therapy in Leber hereditary optic neuropathy.

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to optic atrophy due to degeneration of the retinal ganglion cell. A curative treatment is not available at the moment, but a new antioxidant drug, Idebenone, is expected to reduce the progression of the disorder. Two male patients, genetically confirmed with LHON, were clinically, morphologically, and electrophysiologically evaluated, before and three, six, nine and 12 months after starting the treatment. The patient with 3460G>A mutation in mitochondrially-encoded nicotinamide adenine dinucleotide, reduced form (NADH):ubiquinone oxidoreductase core subunit (mtND)1 gene showed an improvement in visual acuity, visual field, and visual evoked potentials with no effect on morphological examinations, while the patient with 11778G>A mutation in mtND4 gene showed no functional, nor morphological recovery after one year of treatment. This study demonstrates that Idebenone, depending on the genetic profile of the disease, may be effective in functional improvement in patients with LHON.

Locally advanced choroidal melanoma with favorable molecular prognosis - case report.

Uveal malignant melanoma is a rare malignant tumor comprising less than 5% of melanoma cases. It is nevertheless the intraocular tumor with the highest incidence in adults, that arises from the melanocytes in the uveal tract. The authors present the case of a patient with locally advanced choroidal melanoma: from presentation to diagnosis, treatment, and prognosis. A 63-year-old female patient presented in the Ambulatory of the Emergency County Hospital, Craiova, Romania, on the February 1, 2021, accusing visual acuity drop and photophobia in her left eye for about three weeks. Pathology examination in Hematoxylin-Eosin (HE) staining reveals a dense cell proliferation, with small and medium spindle cells and pigment production. The following immunohistochemical markers were used in our study: human melanoma black 45 (HMB45), Ki67, cyclin D1, B-cell lymphoma 2 (Bcl2), S100, Wilms' tumor 1 (WT1), p16, and p53. Uveal melanoma is a malignant tumor that can arise in all the uveal components: iris, ciliary body, and choroid. Out of the three components, iris melanomas have the best prognosis, while ciliary body melanomas have the worst prognosis. It is mandatory for the patient to respect the follow-up schedule, as follow-ups can provide early diagnosis of eventual metastasis.