Andrea Sodi

Color Doppler imaging in evaluation of optic nerve blood supply in normal and glaucomatous subjects

The authors evaluate by means of Color Doppler Imaging (CDI) the blood flow in ophthalmic artery, posterior ciliary arteries and central retinal artery in a group of glaucomatous patients. The data obtained in this study show a statistically significant reduction of the mean systolic peak flow velocity in ophthalmic artery in glaucomas in comparison with controls. In Glaucomatous patients with uncontrolled IOP there was a reduction of end-diastolic flow velocities and a rise of resistivity index in ciliary arteries and central retinal artery.

Ocular manifestations of Fabry's disease: data from the Fabry Outcome Survey.

Background: Fabry’s disease is an X-linked lysosomal storage disorder characterised by deficient activity of the enzyme α-galactosidase A. Aim: To study eye abnormalities in patients with Fabry’s disease in the Fabry Outcome Survey (FOS). Methods: This is the largest study of ocular manifestations in patients with Fabry’s disease. In all, 173 of the 688 patients enrolled in FOS underwent a detailed ophthalmic examination, with a special focus on abnormalities of the cornea, lens, conjunctival and retinal vessels. Results: Cornea verticillata was reported in 76.9% of females and 73.1% of males; vessel tortuosity was observed in 21.9% of females and in 48.7% of males. Fabry cataract was recorded in 9.8% of females and in 23.1% of males. Cornea verticillata was therefore the most frequently reported ophthalmic abnormality in Fabry’s disease in both hemizygotic males and heterozygotic females. Tortuous conjunctival and retinal vessels and Fabry cataract were more frequently found in males than in females. Vessel tortuosity was more frequently observed in patients with a higher severity score and greater impairment of renal and cardiac function, suggesting that it may be associated with a more severe disease. The youngest patient with ocular changes was 3 years old. The prevalence of tortuous vessels in males increased with age. Conclusion: The presence of cornea verticillata is a useful aid in the diagnosis of Fabry’s disease, as it is often present at the time of diagnosis. Vessel tortuosity may have some predictive value for systemic involvement.

Nitric oxide proxies and ocular perfusion pressure in primary open angle glaucoma

Background: To investigate the levels of nitric oxide (NO) markers in plasma and aqueous humour of patients with primary open angle glaucoma (POAG) and their relation to ocular perfusion pressure. Methods: Cyclic guanosine monophosphate (cGMP) and nitrite (NO2 −) were determined in plasma and aqueous humour of 38 patients with POAG and 46 controls. Blood pressure and IOP were measured to calculate ocular perfusion pressure (PP). Results: cGMP and NO2 − plasma levels were significantly decreased in glaucoma patients compared with controls (p = 0.001 v p = 0.004). In the aqueous humour of subjects with POAG, cGMP and NO2 − concentrations were also lower than in normal eyes (p = 0.0001 v p = 0.001). There was a linear association between cGMP in plasma and aqueous humour in glaucomas and controls (r = 0.514, p = 0.029 and r = 0.558, p = 0.004) and this relation differed in the two groups (p = 0.003). Considering glaucoma patients with controls, a positive correlation was found between cGMP and PP (r = 0.379, p = 0.01) and between NO2 − and PP (r = 0.339, p = 0.040). The cGMP/PP correlation was of borderline statistical significance in controls (p = 0.050), whereas it did not attain statistical significance in POAG, as well as the association between NO2 − and PP when glaucomas and controls were considered separately. Conclusions: The authors found alterations of NO markers in the plasma and aqueous humour of glaucoma patients. Primary or secondary impaired NO balance could alter ocular perfusion pressure.

Possible Correlations of Ocular Blood Flow Parameters with Intraocular Pressure and Visual-Field Alterations in Glaucoma: A Study by Means of Color Doppler Imaging

The authors evaluated, by means of color Doppler imaging, the blood flow of the ophthalmic artery, ciliary arteries and central retinal artery in normal and glaucomatous subjects. In normals they found that flow velocities of all considered vessels progressively decline while resistivity indices increase with advancing age. In glaucomatous subjects there was a statistically significant reduction of the mean systolic peak flow velocity of the ophthalmic artery in comparison with normals. Glaucomatous eyes with uncontrolled IOP and with visual-field worsening showed a statistically significant decrease in the end-diastolic flow velocities and an increase in the resistivity index values in ciliary arteries.

Correlation between Photoreceptor Layer Integrity and Visual Function in Patients with Stargardt Disease: Implications for Gene Therapy

PURPOSE To perform a clinical characterization of Stargardt patients with ABCA4 gene mutation, and to investigate the correlation between the inner and outer segment (IS/OS) junction morphology and visual acuity, fundus lesions, electroretinogram abnormalities, and macular sensitivity. METHODS Sixty-one patients with Stargardt disease (STGD) were given a comprehensive ophthalmic examination. Inner-outer photoreceptor junction morphology evaluated by spectral-domain optical coherence tomography was correlated with visual acuity, fundus lesions, fundus autofluorescence, full-field and multifocal electroretinography responses, and microperimetric macular sensitivities. We classified STGD patients into three groups: (1) IS/OS junction disorganization in the fovea, (2) IS/OS junction loss in the fovea, and (3) extensive loss of IS/OS junction. Mutation analysis of the ABCA4 gene was carried out by sequencing the complete coding region. RESULTS A significant difference in visual acuity was observed between IS/OS groups 1 and 2 and between IS/OS groups 2 and 3 (P < 0.0001). A significant difference in microperimetry sensitivity was observed between IS/OS groups 2 and 3, and between IS/OS groups 1 and 3 (P < 0.0001). There was also a statistically significant correlation between IS/OS abnormalities and the extent of fundus lesions (Spearman P ≤ 0.01), as well as with the type of ERG and multifocal ERG results (Spearman P ≤ 0.01). Finally, the degree of IS/OS junction preservation showed a statistically significant correlation with the extension of foveal abnormalities assessed by fundus autofluorescence imaging (Spearman P ≤ 0.01). The G1961E mutation was more frequent in the patients without extensive loss of IS/OS junction (P = 0.01) confirming its association with a milder STGD phenotype. CONCLUSIONS The results of this study suggest that a comprehensive approach in the examination of Stargardt patients has the potential to improve the understanding of vision loss and may provide a sensitive measure to evaluate the efficacy of future experimental therapies in patients with STGD.

Genetic determinants of fasting and post-methionine hyperhomocysteinemia in patients with retinal vein occlusion

INTRODUCTION Moderate hyperhomocysteinemia is considered a risk factor for both venous and arterial thrombosis. A prevalence of up to 30% of fasting hyperhomocysteinemia has been recently reported in patients with retinal vein occlusion (RVO) whereas conflicting data exist on the role of C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene as a risk factor for RVO. No report has been published on cystathionine beta-synthase (CBS) 844ins68 polymorphism (another genetic determinant of blood Hcy levels) in RVO patients. Moreover, scarce information is available on the usefulness of measuring homocysteine also after methionine loading to increase the diagnostic efficacy of hyperhomocysteinemia in RVO patients. MATERIALS AND METHODS In 55 consecutive patients with diagnosis of RVO and 65 matched controls, plasma fasting total homocysteine (Hcy) levels and CBS and MTHFR polymorphisms were evaluated. In patients with normal fasting Hcy levels, post-methionine Hcy levels were determined. RESULTS Moderate fasting hyperhomocysteinemia was detected in 18/55 patients (32.7%). In the remaining 37 patients, Hcy was measured again post-methionine loading (PML). Only 3/37 (8.1%) patients had PML hyperhomocysteinemia. Thus, the total prevalence of moderate hyperhomocysteinemia in this cohort of RVO patients was 21/55 (38.2%). The prevalence of homozygosity for C677T MTHFR genotype, but not that of heterozygosity for CBS844ins68, was significantly higher in RVO patients than in controls. CONCLUSIONS Differently from what has been reported for arterial and/or venous thrombosis, a single fasting Hcy measurement is able to detect most of RVO patients (85.7%) with moderate hyperhomocysteinemia. C677T MTHFR, but not CBS 844ins68, genotype may play a role as risk factor for RVO.

Retinal vein occlusions: a review for the internist

Retinal vein occlusion (RVO) is a disease that is often associated with a variety of systemic disorders including arterial hypertension, diabetes mellitus, dyslipidemia and systemic vasculitis. There are various types of RVO, categorized on the basis of the site of occlusion and on the type of consequent vascular damage. Central retinal vein occlusion (CRVO) is the most clinically relevant type of RVO. In addition to well-known classical risk factors, new thrombophilic factors have been investigated in patients with RVO. Data concerning a number of the parameters remain contradictory; yet, hyperhomocysteinemia and vitamins involved in methionine metabolism appear to play a significant role in the pathogenesis of this disease. Alterations in the fibrinolysis pathway (elevated levels of PAI-1 and Lipoprotein (a)), together with haemorheologic modifications have been recently consistently associated with the disease. Medical treatment includes identification and correction of vascular risk factors. In addition, LMWHs appear to be the best therapeutic approach even if based on a limited number of trials, conducted on a limited number of patients. No data are available on the possible role of antithrombotic strategies in the long-term prevention of recurrent RVO or vascular events.

Effects of timolol and dorzolamide on retrobulbar hemodynamics in patients with newly diagnosed primary open-angle glaucoma.

The authors considered a group of patients with newly diagnosed primary open-angle glaucoma studying the effects of a 4-week treatment with timolol or dorzolamide on retrobulbar vessels. Ocular hemodynamics were assessed by means of color Doppler imaging of the ophthalmic artery, the temporal short posterior ciliary arteries (SPCAs) and the central retinal artery. For each vessel, systolic and diastolic blood flow velocities were measured, and the resistivity index (RI) was calculated. The only significant result was a reduction of temporal SPCA RI after dorzolamide treatment in comparison with baseline (p = 0.011). In the same group, dorzolamide treatment had a slight and nonsignificant increase in temporal SPCA diastolic velocity. The resistance decrease observed after dorzolamide treatment in the ciliary circulation may be due to the decrease in intraocular pressure or a possible direct vasodilating effect of the drug.

Ocular haemodynamics in glaucoma associated with high myopia.

AbstractThe ocular blood flow of a group of high myopic and glaucomatous eyes has been investigated by means of the Color Doppler Imaging (CDI) technique, comparing the results with those of some very myopic eyes without glaucoma, some non-myopic glaucomatous eyes and with a control group. The Ophthalmic Artery (OA), the Short Posterior Ciliary Arteries (SPCAs) and the Central Retinal Artery (CRA) were considered. For every vessel, peak systolic velocity (SV), end-diastolic velocity (DV) and the Pourcelot Resistivity Index were studied. The statistical analysis was performed by means of t-test according to Bonferroni procedure for multiple comparisons. The authors registered in the group of eyes with glaucoma associated with very severe myopia some abnormalities of the OA blood flow systolic velocity which might be interpreted as a vascular risk factor for the pathogenesis of the glaucomatous opticneuropathy; these abnormalities are more severe in glaucoma patients with high myopia than in anage-matched group of glaucoma patients without myopia.

Atherosclerotic and thrombophilic risk factors in patients with ischemic central retinal vein occlusion.

Purpose: To investigate atherosclerotic and thrombophilic risk factors in patients affected by acute ischemic and nonischemic central retinal vein occlusions (CRVOs). Methods: One hundred and three patients with acute unilateral CRVO (41 ischemic and 62 nonischemic) were studied. The frequency of traditional cardiovascular risk factors was assessed, and the plasma levels of a variety of thrombophilic markers were measured. Univariate logistic regression was performed to determine risk factors for ischemic CRVO. Results: Arterial hypertension, hypercholesterolemia, postmethionine hyperhomocysteinemia (HHcy), elevated factor VIII, and reduced folic acid and B6 plasma levels were more frequent in patients with ischemic CRVO than in those with nonischemic CRVO (P = 0.030, P = 0.025, P = 0.011, P < 0.001, P < 0.001, and P = 0.044, respectively). Risk factors for ischemic CRVO were arterial hypertension (odds ratio [OR], 3.22; 95% confidence interval [CI], 1.13-9.21; P = 0.037), hypercholesterolemia (OR, 3.03; 95% CI, 1.06-8.65; P = 0.042), reduced folic acid levels (OR, 6.77; 95% CI, 1.59-28.79; P = 0.011), and elevated FVIII levels (OR, 6.17; 95% CI, 2.56-14.82; P < 0.001). Postmethionine HHcy was associated with low folic acid levels (r = −0.413; P = 0.007; OR, 9.33; 95% CI, 2.06-42.18; P = 0.005). Conclusion: The results of the present study suggest that some atherosclerotic and thrombophilic risk factors may increase the risk of having an ischemic form of CRVO.