Search

Aim: Choroidal perfusion, affected in age related macular degeneration (AMD), is difficult to objectively assess given the overlying retinal circulation. This study more objectively compared choroidal perfusion parameters in a group with non-neovascular AMD to an unaffected age matched control group. Methods: 21 non-neovascular AMD subjects and 21 age matched control subjects without evidence of AMD underwent assessment of their choroidal blood flow in a case-control study. Scanning laser ophthalmoscope indocyanine green (ICG) angiograms were analysed by a new area dilution analysis technique. Four areas in the perifoveal region and two areas in the temporal peripapillary retina were evaluated by producing a graph of intensity of fluorescence of each area over time. The mean of the filling times and the heterogeneity of the filling times were assessed. Results: The means of the filling times within the perifoveal regions and the hetereogeneity of the filling times between regions within the same eyes were significantly greater in the AMD patients compared with the control subjects. Conclusions: Delayed and heterogeneous filling of the choroid was objectively demonstrated in eyes with non-neovascular AMD compared with age matched controls without evidence of AMD, using an area dilution analysis technique applied to ICG angiography.

Blacks in comparison with whites are at risk for a more serious form of hypertension with high rates of complications. Greater sodium retention is thought to underlie the blood pressure (BP)-determining physiology of blacks, but specific mechanisms have not been identified. In a prospective observational study of BP, 226 black children and 314 white children (mean age, 10.6 years) were enrolled initially. Assessments were repeated in 85 blacks and 136 whites after reaching adulthood (mean age, 31 years). The relationship of BP to plasma aldosterone concentration in the context of the prevailing level of plasma renin activity was studied in blacks and whites. In a secondary interventional study, 9-α fludrocortisone was administered for 2 weeks to healthy adult blacks and whites to simulate hyperaldosteronism. BP responses in the 2 race groups were then compared. Although black children had lower levels of plasma renin activity and plasma aldosterone, their BP was positively associated with the plasma aldosterone concentration, an effect that increased as plasma renin activity decreased ( P =0.004). Data from black adults yielded similar results. No similar relationship was observed in whites. In the interventional study, 9-α fludrocortisone increased BP in blacks but not in whites. In conclusion, aldosterone sensitivity is a significant determinant of BP in young blacks. Although its role in establishing the risk of hypertension is not known, it could be as relevant as the actual level of aldosterone.

The most abundant viral mRNA species in HPV 11-infected tissue consists of two exons, joining a segment of open reading frame (ORF) E1 to ORF E4, potentially encoding the E1 up angle E4 protein. The L1 ORF encodes the major capsid protein of HPV. Our previous studies demonstrated colocalization of the HPV 11 E1 up angle E4 and L1 proteins within the same cells of HPV 11-infected human foreskin implants grown in athymic mice (the mouse xenograft system) and removed 12 weeks after implantation. Prior studies have demonstrated E1 up angle E4 transcripts early in infection and throughout the HPV 11-infected epithelium, while L1 transcripts are detected later, and in a subset of E1 up angle E4 mRNA-positive differentiated epithelial cells. Therefore, E1 up angle E4 protein may be produced at an earlier time point or in less differentiated cells than the L1 protein. To study these questions, athymic mice were implanted with HPV 11-infected human foreskin fragments. Mice were sacrificed at 1-week intervals beginning 2 weeks after implantation of tissue. The E1 up angle E4 and L1 proteins colocalized to the same differentiated epithelial cells or to tight clusters of cells in differentiated epithelial layers of HPV 11-infected implants. The E1 up angle E4 and L1 proteins were first detected 4 weeks after implantation. E1 up angle E4 protein was detected in the region of the cell membrane and cytoplasm, and never in the nucleus. L1 protein was only detected in the nucleus. Both proteins were detected in implants containing high viral copy numbers. No specific histologic changes were uniformly associated with detection of these proteins. The tight coupling of the E1 up angle E4 and L1 proteins at multiple time points suggests that expression of both proteins is necessary to complete the virus life cycle.

Aims: To report the effects of intravitreal triamcinolone acetonide (iTAAC) injections as an adjunctive treatment to photodynamic therapy (PDT) with verteporfin for new subfoveal choroidal neovascularisation (CNV) in age related macular degeneration (AMD). Methods: We retrospectively reviewed the records of all AMD patients who had iTAAC within 6 weeks of their first PDT and had a follow up of one year or longer. The proportion of eyes after one year follow up that lost or gained ⩾15 and ⩾30 ETDRS letters, baseline and one year lesion greatest linear dimension (GLD), number of PDTs, and side effects were assessed. Results: Fourteen patients were evaluated. Eleven received one initial combined treatment and three received an additional combined treatment after 6 months. Median follow up was 18 months (range 12 to 25 months). Overall, 7% gained ⩾30 letters, 50% maintained stable vision, 14% lost 15–29 letters, and 29% lost ⩾30 letters. Overall, mean GLD increased from 2580 (SD 1088) µm to 3946 (SD 1503) µm (p = 0.01). The mean number of PDTs during the first year was 2.57. Side effects were mild intraocular pressure elevation in 28.5% and cataract progression in 50% of phakic eyes. Conclusions: iTAAC with PDT in AMD was found to be relatively safe and had reasonable results for lesions with some classic component.

Aim: To comprehensively evaluate the effects of dorzolamide on the choroidal and retinal circulation in patients with age related macular degeneration (AMD). Methods: In this randomised, double masked, parallel study, 36 non-exudative AMD patients were randomised in a 2 to 1 fashion to placebo versus topical dorzolamide and underwent assessment of their choroidal and retinal circulation. Scanning laser ophthalmoscope indocyanine green angiograms (ICGA) were analysed by a new area dilution analysis technique. Four areas in the perifoveal region and two areas in the temporal peripapillary region were evaluated by plotting intensity of fluorescence of each area over time. The means of the choroidal filling times and the heterogeneity of the filling times were assessed. Scanning laser ophthalmoscope fluorescein angiography (FA) was evaluated for retinal arteriovenous passage (AVP) times by plotting intensity of fluorescence of retinal vessels over time. Assessment was performed at baseline and at 4 months. Results: Compared to placebo, AMD patients treated with dorzolamide showed a significantly increased rapidity of choroidal filling in the superior and inferior peripapillary regions (p=0.007, p=0.02, respectively). No significant difference in choroidal filling times was found in any of the perifoveal areas (p=0.9). Also, on FA assessment, treatment with dorzolamide showed no statistical differences in AVP times (p=0.19). Conclusions: Dorzolamide may increase peripapillary choroidal perfusion in non-exudative AMD patients. Further studies are merited.

Background: Laser treatment of extrafoveal well delineated choroidal neovascularisation in exudative age related macular degeneration has a high rate of failure with subsequent severe vision loss from subfoveal involvement. Laser treatment may limit scotoma size, but is unpalatable because of early persistent vision loss. Intravitreal triamacinolone injection may be an acceptable alternative therapy in such disparate cases. Methods: 14 consecutive patients with recurrent neovascularisation were treated with a single 4.0 mg injection of triamacinolone and followed for up to 1 year. Visual results were compared with published data from the Macular Photocoagulation Study of recurrent neovascularisation. Results: Mean visual acuity remained stable at about 20/200 throughout the study period in the treated patients. This is comparable to the outcomes in the Macular Photocoagulation Study for laser retreated patients, and better than the observation group. Conclusions: Intravitreal triamcinolone may be an acceptable treatment of subfoveal recurrent neovascularisation while avoiding early persistent vision loss from laser retreatment.

Background: Information on concentrations of retinal carotenoids (macular pigment, or MP) is of particular interest because MP protects against age-related macular degeneration, the leading cause of irreversible blindness in the United States. Objective: This study was designed to evaluate the relation between dietary intake, blood concentrations, and retinal concentrations of carotenoids in a large group of volunteers. Design: Two hundred eighty volunteers in the Indianapolis area completed health and diet questionnaires, donated a blood sample, and participated in MP density assessment to determine retinal carotenoid status. Dietary intake was assessed by food-frequency questionnaire. Serum concentrations of lutein, zeaxanthin, and � -carotene were measured by HPLC. MP optical density (MPOD) was determined psychophysically with a 460-nm, 1 � test stimulus. Results: Average MPOD was 0.21 ± 0.13. Average intakes of lutein + zeaxanthin and � -carotene were 1101 ± 838 and 2935 ± 2698 � g/d, respectively. Although several key dietary intake variables (eg, lutein + zeaxanthin and � -carotene) differed by sex, no significant sex differences were found in either serum concentrations of lutein and zeaxanthin or MPOD. Serum � -carotene concentrations were significantly higher in women than in men. Serum lutein + zeaxanthin and dietary intake of lutein + zeaxanthin were significantly correlated and significantly related to variations in MPOD (r = 0.21, P < 0.001, and r = 0.25, P < 0.001, respectively). Conclusions: Retinal carotenoids can be measured in epidemiologic studies. In this study, MPOD was associated with lutein + zeaxanthin in the diet and the serum. Retinal concentrations, however, were influenced by other factors as well. To understand the effect of dietary lutein + zeaxanthin intake on the retina and risk of agerelated eye disease, future studies should include measures of macular concentrations of these pigments. Am J Clin Nutr 2001;74:796‐802.

The associations between the intake of the fat-substitute olestra and the concentrations of macular carotenoid pigments and serum lutein and zeaxanthin were investigated in a volunteer cross-sectional sample in Indianapolis. The study was conducted in January through March, 1998 after olestra-containing savory snacks had been sold in central Indiana for a year. Volunteers (n = 280) aged 18-50 y were recruited to make a single clinic visit during which macular pigment optical density (MPOD) was determined by psychophysical flicker photometry, serum was obtained for determination of lutein and zeaxanthin concentration, usual intake of olestra, carotenoids and nutrients were assessed by 1-y food frequency questionnaire, and health habits including smoking, physical characteristics such as eye color, demographics and medical history were determined by questionnaire. Intake of olestra at least one time per month for the past year was reported by 81:280 subjects and their mean, median and 90(th) percentile intakes were 1.09, 0.34 and 2.43 g olestra/d, respectively. Mean macular pigment optical density was not significantly different between olestra consumers and nonconsumers (0.213 +/- 0.014 vs. 0.211 +/- 0.010) nor was serum lutein and zeaxanthin concentration (0.361 +/- 0.017 vs. 0.375 +/- 0. 013 micromol/L) or intake (1242 +/- 103 mg/d vs. 1042 +/- 58 mg/d) in one-way or two-way ANOVA. Olestra intake was not associated with MPOD or serum lutein and zeaxanthin before or after correction for significant covariates of MPOD. Thus, olestra intake over the past year in a cross-sectional volunteer sample in Indianapolis was not associated with MPOD.

Detection of E1AE4 protein in human papillomavirus (HPV 11)-infected tissue is tightly linked to detection of L1 major capsid protein. The only L1-containing transcript identified in HPV 11-infected tissue is the bicistronic E1AE4AL1 mRNA, potentially encoding both the E1AE4 and the L1 proteins. It has not been established that these proteins can be expressed from the E1AE4AL1 transcript. The HPV 11 E1AE4AL1 sequence was cloned by reverse transcriptase polymerase chain reaction into the p1393 vector to produce recombinant baculoviruses. Immunoblots of recombinant baculovirus-infected Sf9 cell lysates demonstrated both the E1AE4 and the L1 proteins. An ELISA was performed on infected Sf9 cells using a monoclonal antibody specific for nondenatured L1, demonstrating that 10 ng of native L1 protein was present per microgram of total nuclear protein. Electron microscopic analysis revealed 50- to 60-nm icosahedral virus-like particles. In vitro transcription/translation was performed using pSPORT constructs containing the E1AE4AL1 sequence or, as controls, monocistronic pSPORT-E1AE4 or L1 constructs. The pSPORT-E1AE4AL1 construct produced the E1AE4 and L1 proteins at a ratio of 17:1. For E1AE4 protein, expression was greater from the pSPORT-E1AE4AL1 construct than from the monocistronic pSPORT-E1AE4 construct. In contrast, more L1 protein was expressed from pSPORT-L1 than from pSPORT-E1AE4AL1. A mutant E1AE4AL1 construct containing no E1AE4 start codon expressed L1 protein in amounts nearly equal to that expressed from the pSPORT-L1 construct. Addition of an antisense oligonucleotide directed at the E1AE4 start codon region to in vitro reactions using pSPORT-E1AE4AL1 was associated with inhibition of E1AE4 protein synthesis and increased translation of L1 protein.