Hemoglobin levels are associated with retinal vascular caliber in a middle-aged birth cohort.

Vascular and neural structures of the retina can be visualized non-invasively and used to predict ocular and systemic pathologies. We set out to evaluate the association of hemoglobin (Hb) levels within the national reference interval with retinal vascular caliber, optical coherence tomography (OCT) and visual field (VF) parameters in the Northern Finland 1966 Birth Cohort (n = 2319, 42.1% male, average age 47 years). The studied parameters were evaluated in Hb quintiles and multivariable linear regression models. The lowest Hb quintile of both sexes presented the narrowest central retinal vein equivalent (CRVE) and the healthiest cardiometabolic profile compared to the other Hb quintiles. In the regression models, CRVE associated positively with Hb levels in both sexes, (Bmales = 0.068 [0.001; 0.135], Bfemales = 0.087 [0.033; 0.140]), after being adjusted for key cardiometabolic and inflammatory parameters, smoking status, and fellow vessel caliber. No statistically significant associations of Hb levels with central retinal artery equivalent, OCT or VF parameters were detected. In conclusion, Hb levels were positively and specifically associated with CRVE, indicating that Hb levels are an independent factor affecting CRVE and the effect is in parallel with established risk factors for cardiometabolic diseases.

Retinal neural tissue and vascular calibres in migraine: the Northern Finland Birth Cohort Eye Study.

PURPOSE: To evaluate the possible effects of migraine on retinal nerve fibre layer (RNFL), ganglion cell-inner plexiform layer (GC-IPL), macular thickness and retinal arteriolar and venular diameters (CRAE, CRVE) in a population-based birth cohort. METHODS: 375 migraineurs and 1489 healthy controls were included in this cross-sectional cohort study. RNFL, GC-IPL and macular thickness parameters were measured by spectral domain optical coherence tomography (OCT), and vascular parameters were measured from fundus photographs. Migraine was determined by a questionnaire and specific features were selected as covariates (gender, smoking status, systolic blood pressure, refraction and diabetes). RESULTS: There were no statistically significant differences between healthy controls and migraineurs in average RNFL (p = 0.123), macular (p = 0.488) or GC-IPL (p = 0.437) thickness. Migraine did not have a significant effect on any of the macular or GC-IPL subfields. For RNFL subfields, only temporal inferior was borderline significantly increased in migraineurs (p = 0.039) in adjusted results. No statistically significant differences were found between study groups on retinal vascular calibres CRAE (p = 0.879), CRVE (p = 0.145) or AVR (p = 0.259). GC-IPL thickness was found to be positively correlated with CRAE and CRVE in both study groups as GC-IPL thickness increased together with the increase in CRAE and CRVE (p-trend < 0.001 in both), and a similar trend was detected with central macular subfield thickness and systolic (p-trend < 0.001) and diastolic (p-trend = 0.010) blood pressure, but only in the control group. CONCLUSION: There were no remarkable differences between migraineurs and healthy controls in retinal vascular or structural parameters in our study.

Prevalence of residual amblyopia in adulthood and its association on educational outcome and quality of life in the Northern Finland Birth Cohort.

PURPOSE: The purpose of the current study was to evaluate the prevalence of residual amblyopia in adults in a population screened and treated in childhood. We also wanted to evaluate the association of amblyopia on school success, level of education, and quality of life. METHODS: This is a follow-up study of 2708 subjects of the Northern Finland Birth Cohort. At the age of 46, the subjects took part in ophthalmic examinations, including the measurement of best-corrected visual acuity (BCVA) and refraction. Residual amblyopia was defined as BCVA 20/30 or less (logMAR ≥0.2) in one or both eyes or a two-line interocular visual acuity difference and absence of any pathological ocular factors. The quality of life was assessed with a 15D questionnaire, and educational outcome, school success, and episodic memory with a CANTAB-PAL (paired associates learning) test were evaluated. RESULTS: The prevalence of amblyopia in the current adult population aged 46 years was 1.3% (n = 36). At 14 years, the amblyopia subjects had had significant differences in mean spherical equivalent between the amblyopic and fellow eye and strabismus more often than controls. No significant differences were observed in the CANTAB-PAL test or in educational outcome. However, amblyopia subjects had significant difficulties in the 15D questionnaire in terms of vision (54% vs. 34%, p = 0.01). CONCLUSION: Due to screening and treatment in childhood, the number of adults with residual amblyopia was low. Despite minor visual impairment and discomfort, they cope very well in life in terms of educational outcome and quality of life.

Correlation of iCare ic100 tonometry with iCare TA01i in screening of unselected population in Northern Finland Birth Cohort Eye study.

PURPOSE: iCare tonometers are easy-to-use and portable devices for measuring the intraocular pressure (IOP). Purpose was to evaluate the IOP values measured by both novel iCare ic100 and conventional model TA01i devices in unselected population. METHODS: IOP was measured with iCare ic100 and TA01i tonometers in 149 participants aged 32-33 years (born in 1985 or 1986) of the Northern Finland Birth Cohort Eye 2 study. The right eye of each participant was selected for analysis. We also collected data on axial length, corneal curvature and central corneal thickness (CCT). Bland-Altman plot was used for comparing the values obtained by these devices. RESULTS: Mean IOP measured with the ic100 device was 13.8 (3.4) mmHg, with TA01i it was 12.5 (3.0) mmHg. The mean difference between these devices was 1.30 mmHg (p < 0.001) and R2 was 0.694. In Bland-Altman analysis, the agreement between the two tonometers ic100 and TA01i was constantly good (mean difference -1.30, ic100 device showing higher measures). There was a correlation between IOP and CCT (r = 0.269, p < 0.001 for ic100 and r = 0.255, p = 0.002 for TA01i), but not with IOP and corneal curvature or IOP and axial length. CONCLUSION: In summary, we found ic100 rebound tonometry to be both reliable and effective, although CCT may influence IOP measurements with ic100 and TA01i. Therefore, iCare ic100 is suitable for IOP measurement in large cohort studies.

Icare versus Goldmann in a randomised middle-aged population : The influence of central corneal thickness and refractive errors.

PURPOSE: The aim of this study was to compare the measurements of intraocular pressure by two tonometers, the Icare rebound tonometer and the Goldmann applanation tonometer, in a randomised screening study. The influence of refraction and central corneal thickness on the measurements was also evaluated. METHODS: Intraocular pressure was measured with rebound tonometer and Goldmann applanation tonometer in 1266 participants; refraction and central corneal thickness were also determined. One randomised eye of each participant was selected for this report's analysis. A Bland-Altman plot was used to compare the values obtained with the two devices. RESULTS: The correlation between rebound tonometer and Goldmann applanation tonometer was good: the intraclass correlation coefficient (r) between the two methods was 0.735 (p < 0.001). The mean difference (rebound tonometer-Goldmann applanation tonometer) was 0.11 ± 2.3 mmHg. The difference was not statistically significant (95% confidence interval: 0.11 to 0.13, p = 0.09). With increasing central corneal thickness, not only did intraocular pressure values with both devices increase, but the difference between them also increased. Refraction (spherical equivalent) did not influence intraocular pressure or the rebound tonometer-Goldmann applanation tonometer difference. However, high astigmatism (≥2D) exerted an influence on intraocular pressure values taken with Goldmann applanation tonometer. CONCLUSION: Measurements with rebound tonometer and Goldmann applanation tonometer are relatively uniform although rebound tonometer slightly overestimated intraocular pressure. Both rebound tonometer and Goldmann applanation tonometer and the difference between these devices were affected by central corneal thickness but not by refraction. Higher astigmatism affected Goldmann applanation tonometer more than rebound tonometer. It is concluded that rebound tonometer is a reliable method for measuring intraocular pressure in a population-based screening study.

Prediabetes influences the structure of the macula: thinning of the macula in the Northern Finland Birth Cohort.

BACKGROUND/AIM: The aim of this study was to evaluate the effect of prediabetes and diabetes on macular thickness and retinal vascular calibres in our population-based cohort (Northern Finland Birth Cohort). METHODS: The population of 2005 individuals was divided into diabetes (n=57), prediabetes (n=1638) and normal glucose metabolism (NGM) groups (n=310). Total thickness of the macula was measured using Cirrus HD-OCT 4000. Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) calibres were measured from the fundus images. The diagnosis of diabetes and prediabetes was made according to WHO 2006 diagnostic standards. RESULTS: Significant macular thinning was observed in subjects with prediabetes (-2.69 µm (95% CI -4.29 to -1.09), p<0.05 and -0.10 mm3 (95% CI -0.16 to -0.04), p<0.05 for macular cube average thickness and cube volume, respectively) and it was greatest in the pericentral area. Macular cube average thickness and macular cube volume decreased significantly by worsening glucose metabolism. Furthermore, CRAE was decreased by increases in 2-hour post-load glucose, glucose area under the curve and increase in Matsuda index (p<0.001, 0.019 and <0.001, respectively). In mediation analysis, macular thickness had significant average causal mediation effect (ACME) on CRVE and CRAE in subjects with prediabetes. CONCLUSION: We detected significant thinning of the macula in subjects with prediabetes. The diameters of retinal arteries were decreased by impaired glucose metabolism. This study provides a new perspective since it revealed that the early and subtle changes caused by prediabetes as macular thinning had significant ACME on retinal vessels, therefore supporting the neurodegenerative theory of diabetes-induced changes in the retina.

Association of glucose metabolism and retinopathy signs in non-diabetic individuals in midlife-The Northern Finland Birth Cohort 1966 study.

Diabetic retinopathy is a microvascular complication of hyperglycaemia. Little is known about the association of glucose metabolism and retinopathy signs in the non-diabetic middle-aged population. We studied prevalence of retinopathy in a subsample of Northern Finland Birth Cohort study (NFBC1966) of 1809 subjects, at 47 years of age, without previously diagnosed type 2 diabetes and/or blood pressure-lowering medication. All participants underwent clinical evaluations including an oral glucose tolerance test (glucose and insulin values measured at 0, 30, 60 and 120 min) and HbA1c. The retinopathy signs were diagnosed by fundus photographs and classified according to the Eurodiab classification scheme. The overall prevalence of newly diagnosed retinopathy was 1.4%. The retinopathy signs were significantly associated with increased 30 min, 1-h and 2-h glucose levels and 2-h insulin level in an OGTT. After adjustment with systolic blood pressure, only 30 min glucose, 1-h glucose and 2-h insulin levels were associated with retinopathy signs. Our findings show the potential role of 30 min and 1-h post-load glucose and 2-h insulin levels as risk factors for retinopathy lesions among the participants without previously diagnosed diabetes or hypertensive medication.

Relation between retinal vessel diameter and posterior segment optical coherence tomography variables in middle-aged Caucasians: the Northern Finland Birth Cohort Eye Study.

AIMS: Studying the relationship between retinal vessel diameter (RVD) with (1) macular thickness and volume, (2) retinal nerve fibre layer (RNFL), (3) ganglion cell-inner plexiform layer (GC-IPL) and (4) optic nerve head (ONH) in a population cohort of middle-aged Caucasians. METHODS: We collected data from 3070 individuals. We used a semiautomated computer-assisted programme to measure central retinal arteriolar equivalent and central retinal venular equivalent. Macular and ONH parameters were assessed by optical coherence tomography. RESULTS: Data from 2155 persons were analysed. A larger RVD was associated with a thicker macula and increased macular volume; each SD increase in average macular thickness and volume was associated with a 3.28 µm and a 3.19 µm increase in arteriolar diameter and a 5.10 µm and a 5.08 µm increase in venular diameter, respectively (p<0.001 for all). A larger rim area, greater GC-IPL and RNFL thicknesses were associated with larger RVD; each SD increase in rim area, GC-IPL thickness and RNFL thickness was associated with a 1.21 µm, 2.68 µm and a 3.29 µm increase in arteriolar diameter and a 2.13 µm, 4.02 µm and 5.04 µm increase in venular diameter, respectively (p<0.001 for all). CONCLUSIONS: Increased macular thickness, macular volume, GC-IPL thickness, RNFL thickness and optic nerve rim area were associated with larger RVDs in all subjects. This study clarified the anatomical correlations between both macular and ONH parameters with RVD for middle-aged Caucasians; these can represent a basis for further studies investigating the vascular aetiology of eye diseases.

Relationship between retinal vessel diameter with both retinal nerve fibre layer thickness and optic nerve head parameters in middle-aged Caucasians: the Northern Finland Birth Cohort Eye study.

PURPOSE: To study the normal relationship between retinal vessel diameter (RVD) with retinal nerve fibre layer (RNFL) thickness and optic nerve head (ONH) parameters in a cohort of middle-aged Caucasians. METHODS: We investigated 3070 individuals (6140 eyes). Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were measured in the right eye using a semi-automated computer-assisted program. Retinal nerve fibre layer (RNFL) thickness and ONH parameters were assessed with Heidelberg retinal tomography (HRT). RESULTS: Data from 2217 persons were analysed including RNFL, CRAE, CRVE, sex, body mass index, mean arterial pressure, diabetes status, smoking status, optic disc area, rim area, spherical refraction and intraocular pressure. A larger RVD was associated with a thicker mean global RNFL thickness especially in global and inferior segments of the retina and with larger optic discs. Each 10 µm increase in the retinal arteriolar calibre was associated with a 5.58 µm increase in mean global RNFL thickness; the corresponding value for a 10 µm increase in venular calibre was 3.79 µm (p < 0.001 for both). Retinal venular calibre displayed consistent associations with RNFL thickness in both genders (p < 0.001 for all), whereas the association of arteriolar calibre and RNFL was more prominent in men (p < 0.001). CONCLUSION: We found strong associations between larger RVD and thicker RNFL in all subjects. This study helps to clarify the association between RVD, RNFL thickness and ONH parameters and provides normal values for middle-aged Caucasians that will help in future studies investigating the role of vascular aetiology in systemic and eye diseases.

Factors Affecting the Visual Outcome of Pituitary Adenoma Patients Treated with Endoscopic Transsphenoidal Surgery.

OBJECTIVE: To evaluate visual acuity (VA) and visual fields (VF) quantitatively before and after endoscopic transsphenoidal surgery (ETS), with special attention to prognostic factors such as the pituitary adenoma (PA) suprasellar extension (SSE), volume and the patients' age. METHODS: Medical records of 47 patients with PA undergoing ETS were evaluated. VA, VF, preoperative visual impairment score (VISpre) and postoperative visual impairment score (VISpost) were determined. The PA SSE, volume, chiasmal contact, and their correlation with visual function were assessed preoperatively and postoperatively. RESULTS: The final cohort included 47 patients. VA improved in 54 of 76 eyes (71.0%) after ETS, and 69 of 76 eyes (90.7%) gained normal VA. Postoperative VF recovery occurred in 32 of 37 eyes (86.5%). The mean change in VIS was 12.0 (95% confidence interval [CI], 7.7-16.3) and improved in all patients with tumor-related visual impairment (n = 25). However, visual outcome was poorer when VISpre was greater than 40. When VISpre was 21-40, age linearly correlated with VIS improvement (P = 0.03); younger patients had satisfactory and older poorer visual outcome. The mean SSE in patients with VF defects (n = 20) was 16.6 mm (95% CI, 13.3-19.9). Mean SSE in patients with no VF defects (n = 23) was 6.6 mm (95% CI, 4.9-8.3; P < 0.001), and the cutoff value for visual perturbations was 9.5 mm for SSE and 8.6 mL for PA volume (P < 0.001 for both). CONCLUSIONS: The visual outcome after ETS for PAs was excellent, and serious complications were rare. Severe preoperative visual impairment resulted in poorer postoperative visual outcomes. The SSE of the PA was the most important predictor of visual outcome after ETS.

Elevated Levels of Plasma IgA Autoantibodies against Oxidized LDL Found in Proliferative Diabetic Retinopathy but Not in Nonproliferative Retinopathy.

Aims. This study investigated the association of autoantibodies binding to oxidized low-density lipoproteins (oxLDL) in diabetic retinopathy (DR). Methods. Plasma from 229 types 1 and 2 patients with DR including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) was analysed with ELISA-based assay to determine IgA, IgG, and IgM autoantibody levels binding to oxLDL. The controls were 106 diabetic patients without retinopathy (NoDR) and 139 nondiabetic controls (C). Results. PDR group had significantly higher IgA autoantibody levels than DME or NoDR: mean 94.9 (SD 54.7) for PDR, 75.5 (41.8) for DME (p = 0.001), and 76.1 (48.2) for NoDR (p = 0.008). There were no differences in IgG, IgM, or IgA that would be specific for DR or for DME. Type 2 diabetic patients had higher levels of IgA autoantibodies than type 1 diabetic patients (86.0 and 65.5, resp., p = 0.004) and the highest levels in IgA were found in type 2 diabetic patients with PDR (119.1, p > 0.001). Conclusions. IgA autoantibodies were increased in PDR, especially in type 2 diabetes. The high levels of IgA in PDR, and especially in type 2 PDR patients, reflect the inflammatory process and enlighten the role of oxLDL and its autoantibodies in PDR.

Interleukin 8 promoter polymorphism predicts the initial response to bevacizumab treatment for exudative age-related macular degeneration.

PURPOSE: To study the association of single-nucleotide polymorphisms of interleukin 8, vascular endothelial growth factor, erythropoietin, complement factor H, complement component C3, and LOC387715 genes with the response to bevacizumab treatment in exudative age-related macular degeneration. METHODS: Clinical records, smoking history, optical coherence tomography, and angiographies of 96 bevacizumab-treated exudative age-related macular degeneration patients were analyzed retrospectively. Blood DNA was collected. Based on the disappearance of intra- or subretinal fluid in optical coherence tomography, patients were graded as responders, partial responders, or nonresponders after 3 initial treatment visits and a median time of 3.5 months. RESULTS: Interleukin 8 promoter polymorphism -251A/T was significantly associated with persisting fluid in optical coherence tomography. The A allele was more frequent in nonresponders than in responders (P = 0.033). In multivariate modeling, the AA genotype of -251A/T (P = 0.043) and occult (P = 0.042) or predominantly classic (P = 0.040) lesions predicted poorer outcome. Visual acuity change was better in responders than in nonresponders (P = 0.006). Baseline lesion size (P = 0.006) and retinal cysts after the treatment (P < 0.001) correlated with less visual acuity gain. CONCLUSION: The A allele and the homozygous AA genotype of interleukin 8 -251A/T were associated with anatomical nonresponse to bevacizumab treatment.

Vascular endothelial growth factor gene variation and the response to photodynamic therapy in age-related macular degeneration.

PURPOSE: To evaluate the role of vascular endothelial growth factor (VEGF) gene polymorphisms in exudative age-related macular degeneration (AMD). DESIGN: Retrospective, comparative case series. PARTICIPANTS: Patients with recent exudative AMD (n = 162) and age-matched subjects without AMD (n = 85). METHODS: Fluorescein angiography (FA), clinical examination, and single nucleotide polymorphism (SNP) genotyping. MAIN OUTCOME MEASURES: The frequencies of 3 VEGF gene SNPs were analyzed, 1 at the promoter site (rs699947, A-->C) and 2 intronic SNPs (rs2146323, A-->C, and rs3025033, A-->G), in relation to the risk of AMD, to choroidal neovascular (CNV) lesion size and configuration, and to the anatomic response to photodynamic therapy (PDT). These SNPs were chosen to cover all the haploblocks of the VEGF gene. The 86 patients who had undergone PDT were classified as either PDT responders or PDT nonresponders based on the outcome of PDT after the last treatment session. For the PDT responders, the treating physician had deemed the lesion to be clinically dry and without leakage from CNV in FA at a visit scheduled at least 12 weeks after the last PDT treatment. For the PDT nonresponders, the PDT sessions had been discontinued by the treating retina specialist because of an apparently poor response and a still exudative lesion after several PDT sessions. RESULTS: The presence of exudative AMD or lesion size or configuration was not associated with the SNPs studied here. The frequencies of the rs699947 were significantly different in PDT nonresponders and PDT responders. The AA, AC, and CC genotypes were 14%, 39%, and 46%, respectively, in PDT nonresponders, compared with 40%, 48%, and 12%, respectively, in the PDT responders (P = 0.0008). The corresponding frequencies for the rs2146323 AA, AC, and CC genotypes were 4%, 32%, and 64%, respectively, in nonresponders and 24%, 38%, and 38%, respectively, in responders (P = 0.0369). The genotypes of the rs3025033 SNP were distributed evenly between the responders and nonresponders. CONCLUSIONS: The VEGF gene polymorphic SNPs at rs699947 and rs2146323 are strong determinants of the anatomic outcome after PDT, but the SNPs studied were not associated with the presence of exudative AMD or with the CNV lesion size or configuration. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Polymorphism of the manganese superoxide dismutase gene but not of vascular endothelial growth factor gene is a risk factor for diabetic retinopathy.

BACKGROUND: In diabetic retinopathy, the vascular endothelium is damaged due to oxidative stress and inflammation, and vitreous VEGF concentration becomes elevated. The association of diabetic retinopathy with single nucleotide polymorphisms (SNPs) was studied on two genes: VEGF, an important mediator of neovascularisation, and MnSOD, a major antioxidant enzyme. METHODS: The study population was 755 individuals consisting of 131 diabetic (type 1 or type 2) patients with diabetic retinopathy (DR group), 98 diabetic controls without retinopathy (DC group) and 526 non-diabetic controls. VEGF SNPs rs699947, rs2010963, rs2146232, rs3025033, rs3025039 and Ala16Val polymorphism of the MnSOD gene were genotyped. RESULTS: The frequencies of allele and genotype of the single genotyped VEGF SNPs or reconstructed haplotypes of these single SNPs did not differ between DR and DC groups. A higher frequency of the AlaAla genotype (p = 0.03) and Ala16 allele (p = 0.04) of the MnSOD gene in the DR group was found when compared with the DC group. CONCLUSIONS: In conclusion, the studied VEGF SNPs were not associated with the risk of diabetic retinopathy, and so it is unlikely that the VEGF gene is a major locus determining the risk of diabetic retinopathy. A statistically significant association of MnSOD Ala16Val polymorphism with diabetic retinopathy was found.

Efficacy and safety levels of preserved and preservative-free tafluprost are equivalent in patients with glaucoma or ocular hypertension: results from a pharmacodynamics analysis.

PURPOSE: Tafluprost is a new prostaglandin F(2alpha) (PGF(2alpha)) derivative in development for the treatment of glaucoma. Tafluprost is the first PGF(2alpha) analogue with a preservative-free formulation. METHODS: This randomized, investigator-masked, multicentre, crossover phase III study evaluated the pharmacodynamics and safety of preserved and preservative-free tafluprost 0.0015% eyedrops administered for 4 weeks in 43 patients with open-angle glaucoma or ocular hypertension. The primary variable was change from baseline in overall diurnal intraocular pressure (IOP) at 4 weeks. Adverse events and other safety parameters were also analysed. RESULTS: Decreased IOP was clearly observed with both formulations at week 1 and was sustained until week 4. The overall treatment difference (preservative-free versus preserved formulations) at week 4 was 0.01 mmHg (95% confidence interval - 0.46 to 0.49; p = 0.96). There were no unexpected safety-related findings. Both formulations were well tolerated and most adverse events were ocular and mild in severity. CONCLUSIONS: THE reduction in IOP achieved by preservative-free tafluprost is equivalent to that obtained with the preserved formulation. The preservative-free formulation was generally well tolerated.

High vitreous concentration of vascular endothelial growth factor in diabetic patients with proliferative retinopathy using statins.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in the development of diabetic retinopathy. Previous studies have suggested that angiotensin-converting enzyme (ACE) inhibitor therapy may reduce vitreous VEGF concentration in diabetic retinopathy. Also HMG CoA reductase inhibitors (statins), known for their beneficial effects on vascular endothelium, might influence vitreous VEGF concentration in diabetic retinopathy. AIM: Vitreous VEGF concentration of diabetic patients with proliferative retinopathy using statin therapy and/or ACE inhibitor therapy was studied. METHODS: Fifty diabetic patients with proliferative diabetic retinopathy, 21 diabetic control patients without proliferative retinopathy, and 43 non-diabetic control subjects underwent vitrectomy. Vitreous samples were collected at the beginning of surgery, and VEGF concentration was assessed using a chemiluminescent VEGF immunoassay. RESULTS: Vitreous VEGF concentration was significantly higher in diabetic patients with proliferative retinopathy using statins than in those not using statins. The diabetic patients with proliferative retinopathy were divided into subgroups according to use of ACE inhibitor and/or statin medication. These groups did not differ significantly in concentration of vitreous VEGF. CONCLUSIONS: Statin therapy is associated with high vitreous VEGF concentration in diabetic patients with proliferative retinopathy. In contrast to previous reports, ACE inhibitor use did not significantly influence vitreous VEGF concentration in these patients.

Defective glycosylation of cholesteryl ester transfer protein in plasma from alcohol abusers.

AIMS: Alcohol consumption reduces the carbohydrate content of some glycoproteins, e.g. carbohydrate-deficient transferrin. The aim of this study was to investigate if there is such an alcohol-induced glycosylation defect in plasma cholesteryl ester transfer protein (CETP). A defect in the posttranslational glycosylation of CETP may affect its structure and electrical charge and may therefore affect its function. CETP activity is low in alcohol abusers. METHODS: We studied the effect of alcohol consumption on CETP properties in 10 alcohol abusers and 10 control subjects. CETP was partially purified from lipoprotein-free plasma by FPLC using a Phenyl-Sepharose column. Isoelectric focusing, polyacrylamide gel electrophoresis, and western blotting were performed for partially purified CETP. RESULTS: CETP had a lower molecular weight in the alcohol abusers than in the controls (range 50.6-84.0 kDa in the alcohol abusers vs 51.3-85.0 kDa in the controls). CETP purified from alcohol abusers had a higher isoelectric point, indicating a lower negative charge on the surface of the protein than in the controls' CETP. A similar effect was observed when control CETP was incubated with neuraminidase, an enzyme which is known to remove sialic acid from glycoproteins. CONCLUSIONS: We conclude that CETP from alcohol abusers may have a glycosylation defect due to defective sialylation caused posttranslationally by alcohol itself or its metabolite acetaldehyde. The defective glycosylation of CETP associated with altered binding to lipoproteins may lead to the low CETP activity observed previously in alcoholic subjects.