Conjunctival Marginal Zone Lymphoma in a Patient With Neurofibromatosis Type 1: A Case Report.

We present a case of painless bulbar conjunctival mass due to B-cell non-Hodgkin lymphoma (NHL), without systemic involvement, in a 76-year-old man. Following an excision biopsy, histopathologic examination and immunohistochemistry confirmed the diagnosis, prompting a referral for hemato-oncological assessment. The patient underwent comprehensive laboratory and imaging scans, subsequently receiving combined chemo-immunotherapy that resulted in complete remission to date. This case is reported as it is crucial to recognize that a conjunctival insult might emerge in neurofibromatosis type 1 (NF1) patients.

Alterations in Retinal Vessel Diameters in Patients with Retinal Vein Occlusion before and after Treatment with Intravitreal Ranibizumab.

Purpose: To investigate the alterations of retinal vessel diameters in patients with macular edema secondary to retinal vein occlusion (RVO), before and after treatment with intravitreal ranibizumab. Methods: Digital retinal images were obtained from 16 patients and retinal vessel diameters were measured before and three months after treatment with intravitreal ranibizumab with validated software to determine central retinal arteriolar and venular equivalents, as well as arteriolar to venular ratio. Results: In 17 eyes of 16 patients with macular edema secondary to RVO (10 with branch RVO and 6 with central RVO) aged 67 ± 10.2 years, we found that diameters of both retinal arterioles and venules were significantly decreased after intravitreal ranibizumab treatment. Specifically, the central retinal arteriolar equivalent was 215.2 ± 11.2 µm at baseline and 201.2 ± 11.1 µm at month 3 after treatment (p < 0.001), while the central retinal venular equivalent was 233.8 ± 29.6 µm before treatment versus 207.6 ± 21.7 µm at month 3 after treatment (p < 0.001). Conclusions: A significant vasoconstriction in both retinal arterioles and venules in patients with RVO was found at month 3 after intravitreal ranibizumab treatment compared to baseline. This could be of clinical importance, since the degree of vasoconstriction might be an early marker of treatment efficacy, compatible with the idea that hypoxia is the major trigger of VEGF in RVO. Further studies should be conducted to confirm our findings.

Pediatric Non-Infectious Uveitis: Long-Term Outcomes and Complications.

PURPOSE: To describe the long-term prevalence of ocular complications and visual prognosis in patients with pediatric uveitis. METHODS: Demographics, etiology and location of uveitis, type of complications, treatment and visual outcomes were recorded in 296 children at first examination and at 1-, 2-, 3-, 5- and 10-year time points. RESULTS: Αnterior uveitis represented 53.4% of cases, followed by intermediate (28.0%), posterior uveitis (11.1%) and panuveitis (7.4%). The leading diagnoses were idiopathic uveitis (31.1%), juvenile idiopathic arthritis (27.0%) and pars planitis (22.6%). Posterior synechiae was the most frequent complication of anterior uveitis and panuveitis, cystoid macular edema and disc edema of intermediate and posterior uveitis respectively. Posterior uveitis and panuveitis had more severe final vision loss (23.1% and 20% respectively). CONCLUSIONS: This study provides clinical characteristics and main complications in a longitudinal long-term follow-up of a large non-infectious pediatric uveitis Greek population. Early diagnosis and close monitoring remain of fundamental importance.

Efficacy and safety of vitamin supplements with resveratrol in diabetic macular edema: Long-term results of a comparative study.

PURPOSE: To investigate the adjunct efficacy and safety of vitamin supplements, including resveratrol, in patients with diabetic macular edema (DME) treated with intravitreal anti-vascular endothelial factor (anti-VEGF) agents. METHODS: Participants in this prospective study were 45 patients with DME, who were treated with either intravitreal anti-VEGF injections (n = 23, Group I) or with combination of intravitreal anti-VEGF injections and vitamin supplements, including resveratrol (n = 22, Group II). All patients underwent visual acuity measurement, slit-lamp examination and spectral domain-optical coherence tomography (SD-OCT) at baseline and monthly after the loading phase of three-monthly anti-VEGF injections, following a PRN protocol. RESULTS: There was a statistically significant improvement in visual acuity in both groups at month 12 compared to baseline, although the mean change in visual acuity did not differ between the two groups (p = 0.183). Accordingly, there was a statistically significant decrease in central retinal thickness in both groups at month 12 compared to baseline, while the mean difference in central retinal thickness was significantly greater in the "combination" group. The mean number of intravitreal anti-VEGF injection was less in Group II (6.45 ± 1.12 in Group II vs. 7.39 ± 1.31 in Group I, p = 0.018). CONCLUSIONS: Vitamin supplements with resveratrol was found to be an effective adjunct to intravitreal anti-VEGF injections in patients with DME, offering better anatomic restoration with less injections at the 12-month follow-up.

Corneal endothelial cells and central corneal thickness in patients with neurofibromatosis type 1.

Purpose: The aim of this study was to evaluate the morphological properties of corneal endothelial cells and central corneal thickness (CCT) in patients with neurofibromatosis type 1 (NF1) and to compare them with age-matched healthy controls. Methods: Nineteen NF1 patients and 38 healthy individuals were recruited. All participants underwent complete ophthalmological examination as well as noncontact specular microscopy to measure endothelial cell density (ECD), average cell area (AVG), coefficient of variation of cell area (CV), the percentage of hexagonal cells, and CCT. Eyes with previous ocular trauma, inflammation or surgery, and preexisting corneal and ocular surface diseases were excluded. Results: NF1 patients had higher ECD compared to healthy controls of the same age (2764.2 ± 270.4 versus 2570.4 ± 449.2 cells/mm, respectively), although at a borderline level (P = 0.051). Patients with NF1 presented significantly lower CV and AVG when compared to controls (32.9 ± 4.6 versus 37.8 ± 9.5%, P = 0.011 and 364.9 ± 34.4 versus 406.0 ± 107.4 µm, P = 0.038, respectively). The NF1 group had significantly higher hexagonality in comparison with controls (55.7 ± 6.5 versus 50.5 ± 9.9%, P = 0.025). CCT was similar between the two groups (P = 0.955). Conclusion: Our results show that corneal endothelium has more favorable morphological characteristics in NF1 patients compared to healthy individuals of the same age.

A Multifactorial Approach in Type 2 Diabetes Over 3 Years Decelerates Progression of Subclinical Arterial Disease in Routine Clinical Practice.

The beneficial effect of multifactorial treatment of cardiovascular (CV) risk factors (RFs) in type 2 diabetes (T2D) is well established from randomized clinical trials. We prospectively evaluated the impact of such treatment in a real-world setting, on the development of subclinical arterial damage (SAD), as determined by structural/functional noninvasive biomarkers of vascular pathology (atheromatosis, carotid hypertrophy, arteriosclerosis). We prospectively studied 116 persons with T2D, treated with a multifactorial approach for CV RFs at a tertiary medical center, and 324 individuals without diabetes, for 3.2 years. The primary outcome was changes in vascular biomarkers related to SAD. At baseline, participants in the diabetes group had higher prevalence of SAD. At study end, the changes in clinical, biochemical, and lifestyle characteristics, as well as antihypertensive and lipid-lowering treatments, were comparable between the 2 groups. During follow-up, classical CV RFs (smoking, blood pressure, low-density lipoprotein-cholesterol, triglycerides) and behavioral features were significantly improved in both groups. Multivariate analysis, after adjusting for all classic CV RFs and use of antihypertensive/lipid-lowering therapies, demonstrated that all evaluated SAD biomarkers were similarly changed in the 2 groups. In conclusion, implementation of a multimodality approach of T2D treatment is feasible and efficacious in decelerating progression of SAD in routine clinical practice.

Biologic Treatment Options for Retinal Neovascularization in Behçet's Disease.

PURPOSE: Relapsing ocular inflammation occurs in about 70% of patients with Behçet's disease (BD) and can lead to permanent loss of vision. Neovascularization of the optic disc (NVD) or elsewhere in the retina (NVE) is a relatively uncommon but severe complication that lacks standardized treatment. METHODS: We report on the therapeutic use of anti-TNF monoclonal antibodies for BD-associated NVD and NVE in one pediatric patient (subcutaneous adalimumab) and one young man (intravenous infliximab). Also, we review the previously published experience on biologic therapeutic options, namely anti-TNF agents and interferon-alpha in a total of three and eight patients, respectively. RESULTS: A fast-onset therapeutic effect was observed in both patients leading to complete regression of neovascularizations. CONCLUSIONS: Both options may lead to regression of neovascularization, thus preventing loss of vision, but comparative studies need to determine the optimal treatment for this sight-threatening complication of BD.

Prognostic value of average home blood pressure and variability: 19-year follow-up of the Didima study.

OBJECTIVE: The current general population study explored the prognostic value of home blood pressure (HBP) average and variability (BPV) versus office measurements (OBP). METHODS: In 1997, 665 adults of Didima, Argolida, Greece were evaluated with OBP (two visits, six readings) and HBP (3 days, 12 readings) measurements. Total mortality and cardiovascular morbidity and mortality (CVD) were assessed after 19.0 ±â€Š1.4 years. BPV was quantified by using SD and coefficient of variation. RESULTS: During follow-up, 216 deaths (124 cardiovascular) and 146 cardiovascular events (fatal and nonfatal) were documented. Hazard ratios for total mortality were 1.39/1.20 (P < 0.01/ < 0.01) per 10/5 mmHg increase in systolic/diastolic HBP and 1.36/1.02 (P < 0.01/NS) for OBP (similar hazard ratios for CVD). After adjustment for baseline risk factors, OBP and HBP lost their prognostic ability, except from diastolic OBP that predicted CVD (hazard ratio 1.10, P = 0.03). Sustained, masked and white-coat hypertension were associated with increased risk of death and CVD (P < 0.01 versus normotensive participants). After adjustment, the risk of death remained significant for all, but CVD only for white-coat hypertension. Systolic home BPV (not diastolic) predicted total mortality (adjusted hazard ratios 1.18/1.17 for 1-SD increase in SD/coefficient of variation; P < 0.05) and CVD. Unadjusted systolic/diastolic office BPV predicted CVD outcome (for total mortality only systolic), yet not after adjustment. Systolic home BPV predicted total mortality and CVD independent of office BPV. CONCLUSION: In this general population study with 19-year follow-up, average HBP predicted total mortality and CVD as reliably as OBP. Only normotension (low OBP and HBP) was associated with low risk. Systolic home BPV exhibited superior prognostic ability than OBP, deserving further research.

Mechanisms of pulse pressure amplification dipping pattern during sleep time: the SAFAR study.

The difference in pulse pressure (PP) between peripheral arteries and the aorta, called pulse pressure amplification (PPamp), is a well-described physiological phenomenon independently associated with cardiovascular events. Recent studies suggest that it exhibits circadian variability. Our aim was to detect the factors associated with the circadian variability of PPamp. In 497 consecutive subjects (aged 54 years, 56.7% male, 79.7% hypertensives), we assessed the circadian pattern of peripheral and central arterial hemodynamics by 24-hour evaluation of brachial and aortic blood pressure (BP), augmentation index (AI), and pulse wave velocity (PWV) using a validated oscillometric device (Mobil-O-Graph). All parameters exhibited a circadian variation. Sleep dipping (decrease) pattern was observed for PPamp, brachial and aortic systolic BP, mean BP, and PWV, whereas a rising pattern (higher sleep than wake values) was observed for brachial PP, aortic PP, and AI. The factors independently associated with the less sleep dipping in PPamp were older age, lower height, the use of antihypertensive medication, and sleep decrease in arterial stiffness (PWV), whereas female gender, the presence of hypertension, sleep increase of pressure wave reflections (AI), sleep decrease in heart rate, and mean BP were associated with a greater sleep-dipping in PPamp. These data provide further pathophysiological understanding of the mechanisms leading to PPamp dipping. Several implications regarding the clinical use of the aortic and brachial BP, especially during sleep time, are raised that should be addressed in future research.

Retinal microcirculation in association with caffeinated and alcoholic drinks in subjects at increased cardiovascular risk.

OBJECTIVES: The association of caffeinated and alcoholic drinks with microcirculation is poorly investigated. The aim of the study was to investigate the associations of daily consumption of caffeinated and alcoholic drinks with retinal vessel calibers. METHODS: In consecutive adults at increased risk but free of CVD and diabetes mellitus, (n=181, age: 51.32±12.42 y, 51.4% women), we determined CRAE, CRVE and AVR, respectively. Daily consumption of caffeinated and alcoholic drinks was assessed through 24 h recalls. RESULTS: After adjustment for potential confounders: (i) caffeine was positively associated with CRVE (b=0.177, P=.006 for left, b=0.208, P=.002 for right eye, respectively) (ii) decaffeinated coffee was positively associated with CRAE (b=0.141, P=.035 for left eye) and negatively associated with CRVE (b=-0.234, P<.001 for left, b=-0.189, P=.006 for right eye, respectively). Regular coffee, tea, alcohol, and any type of alcoholic drink did not associate with retinal vessel calibers. CONCLUSIONS: Alcohol and alcoholic drinks' consumption were not associated, while decaffeinated coffee and caffeine consumption were associated in an opposing pattern with retinal vessel calibers. The reason of this controversy merits further investigation.

Phenotypes of office systolic blood pressure according to both brachial and aortic measurements: frequencies and associations with carotid hypertrophy in 1861 adults.

BACKGROUND/AIM: Aortic SBP (aSBP) associates with arterial damage more consistently than brachial SBP (bSBP). However, it is unknown how often aSBP is normal in the presence of elevated bSBP, and vice versa; if SBP phenotyping on the basis of bSBP and aSBP cut-off values improves cardiovascular risk stratification. We tested the frequency of four office SBP phenotypes: type I (both normal bSBP and aSBP); type II (high bSBP but normal aSBP); type III (normal bSBP but high aSBP), and type IV (both high bSBP and aSBP), the probability of each phenotype to be associated with increased arterial damage, using type Ia (i.e. normal bSBP and low-normal aSBP) as reference. METHODS: In 1861 participants (age: 54 years, 49.1% men), we measured simultaneously bSBP, aSBP, and carotid cross-sectional wall area with ultrasound. RESULTS: Depending on the applied cut-off values, type II and type III phenotypes represented together 5-11% of the population (0.9-3.4 and 1.8-10.3%, respectively) and type IV around 20%. Subgroups with phenotypes, Ib (i.e. normal bSBP and high-normal aSBP), II, III, and IV had gradually significantly higher probability (by 1.37-1.91, 2.3-3.3, 3.3-8.9 times, and 4.18-6.25, respectively) to present elevated carotid artery cross-sectional wall area compared with the reference group, even after adjustment for DBP and other confounders. CONCLUSIONS: Type II (i.e. isolated high bSBP) and type III (i.e. isolated high aSBP) office SBP phenotypes were common and had intermediate level (between types I and IV) of arterial damage.

Mean arterial pressure values calculated using seven different methods and their associations with target organ deterioration in a single-center study of 1878 individuals.

To assess the differences among seven different methods for the calculation of mean arterial pressure (MAP) and to identify the formula that provides MAP values that are more closely associated with target organ deterioration as expressed by the carotid cross-sectional area (CSA), carotid-to-femoral pulse-wave velocity (cf-PWV) and left ventricular mass (LVM). The study population consisted of 1878 subjects who underwent noninvasive cardiovascular risk assessment. Blood pressure (BP) was assessed in all subjects, and MAP was calculated by direct oscillometry and six different formulas. Carotid artery ultrasound imaging was performed in 1628 subjects. The CSA of the right and left common carotid artery (CCA) were calculated and used as surrogates of arterial wall mass and hypertrophy. Aortic stiffness was evaluated in 1763 subjects by measuring the cf-PWV. Finally, 218 subjects underwent echocardiographic examination for the assessment of LVM. Among the examined methods of MAP calculation, the formula MAP1=[diastolic BP]+0.412 × [pulse pressure] yielded the strongest correlations with the LVM, cf-PWV and CSA of the right and left CCA, even after adjusting for age and gender. The MAP calculation using the 0.412 was superior compared with the traditional formula that uses the 0.33 for the discrimination of subjects with left ventricular and carotid wall hypertrophy, as well as subjects with increased aortic stiffness. MAP estimated with the 0.412 is better correlated with target organ deterioration compared with other formulas. Future studies are needed to explore the accuracy of these formulas for MAP estimation compared with direct intra-arterial BP measurement.

Ambulatory Aortic Stiffness Is Associated With Narrow Retinal Arteriolar Caliber in Hypertensives: The SAFAR Study.

BACKGROUND: Arterial stiffness measured under static conditions reclassifies significantly cardiovascular (CV) risk and associates with narrower retinal arterioles. However, arterial stiffness exhibits circadian variation, thus single static stiffness recordings do not correspond to the "usual" 24 hr, awake, and asleep average arterial stiffness. We aimed to test the hypothesis that ambulatory 24 hr, awake, and asleep aortic (a) pulse wave velocity (PWV) associate with retinal vessel calibers, independently of confounders and of static arterial stiffness, in hypertensive individuals free from diabetes and CV disease. METHODS: Digital retinal images were obtained (181 individuals, age: 53.9±10.7 years, 55.2% men) and retinal vessel calibers were measured with validated software to determine central retinal arteriolar and venular equivalents (CRAE and CRVE, respectively); ambulatory (24 hr, awake, asleep) and static office aPWV were estimated by Mobil-O-Graph; and static office carotid to femoral (cf) PWV by SphygmoCor. RESULTS: Regression analysis performed in 320 gradable retinal images showed that, after adjustment for confounders: (i) ambulatory aPWV was significantly associated with narrower retinal arterioles but not with venules; (ii) asleep aPWV had stronger associations with CRAE than awake aPWV; (iii) both ambulatory aPWV and cfPWV were associated mutually independently with narrower retinal arterioles; aPWV introduction in the model of cfPWV, improved model's R2 (P = 0.012). Similar discriminatory ability of 24 hr aPWV and of cfPWV to detect the presence of retinal arteriolar narrowing was found. CONCLUSION: Ambulatory aPWV, estimated by an operator-independent method, provides additional information to cfPWV regarding the associations of arterial stiffness with the retinal vessel calibers.

The Keith-Wagener-Barker and Mitchell-Wong grading systems for hypertensive retinopathy: association with target organ damage in individuals below 55 years.

BACKGROUND: The usefulness of the hypertensive retinopathy classification by Keith-Wagener-Barker (KWB) in clinical practice remains controversial. The simplified Mitchell-Wong grading, combining the two initial KWB' grades in one stage, is proposed as an alternative method; both systems are poorly validated regarding their association with target organ damage. OBJECTIVE: In a population free of cardiovascular disease and diabetes, we aimed to investigate the interobserver and intraobserver agreement of both grading systems, their association with aortic stiffness, carotid hypertrophy or plaques and the role of age and sex on this association. METHODS: Digital retinal images were obtained and graded - according to both classifications - by two independent and blinded observers; aortic stiffness (carotid-femoral pulse wave velocity, m/s) and common carotid hypertrophy (cross-sectional area, mm) or plaques were assessed by tonometry and ultrasound, respectively. RESULTS: From the gradable retinal photos obtained by 200 eyes of 107 consecutive patients (age: 54 ±â€Š13 years, 51% men, 79% hypertensive patients) and after adjustments for confounders, the intraobserver and interobserver level of agreement was as following: KWB 88/64% and Mitchell-Wong 91/71%, respectively; exclusively in younger, not older, individuals aortic stiffness, carotid hypertrophy, but not plaques, were significantly associated with both systems, independently from confounders; no differences regarding target organ damage were found between stages 1 and 2 of KWB. CONCLUSION: Detecting early signs of hypertensive retinopathy may be of value in young individuals; the Mitchell-Wong seems preferable to the KWB classification system only for reasons of simplifying clinical practice.

Intact calibers of retinal vessels in patients with systemic sclerosis.

OBJECTIVE: A primary endothelial cell dysfunction is thought to be involved in systemic sclerosis (SSc)-associated fibroproliferative vasculopathy of the microcirculation and small arterioles, even in sites not affected by fibrosis. Because the role of fibroblasts in pathologic modifications and vascular wall remodeling is relatively unclear, and because the retina provides a unique opportunity to assess microcirculation in the absence of resident fibroblasts, we systematically evaluated retinal vessels in patients with SSc. METHODS: Digital retinal images were obtained from both eyes of 93 consecutive patients with fully characterized SSc and 29 healthy controls matched 1:1 for age and sex with selected patients without diabetes, hypertension history, or antihypertensive treatment. Internal microvascular calibers (erythrocyte column width in µm) by central retinal arteriolar and venular equivalents and arteriolar to venular ratio were measured using validated software. RESULTS: Arteriolar and venular calibers were similar in patients and their matched controls (mean ± SEM; 187 ± 2 vs 184 ± 3, p = 0.444, and 211 ± 2 vs 216 ± 3, p = 0.314, respectively). Both arteriolar and venular calibers and their ratio in patients with SSc were not associated with disease duration, extent of skin involvement, pulmonary fibrosis, digital ulcers or pitting scars, amputations, digital capillaroscopic findings, inflammatory indices, or autoantibodies. CONCLUSION: The evidence that retinal microcirculation is spared in SSc suggests that fibroproliferative vasculopathy may depend on specific cellular or soluble factors not present in the retinal environment.