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Biomedical subjects

T A Ciulla

Publications and source records attributed to T A Ciulla.

At least 19 recordsLinked to original sources

Aging affects the retrobulbar circulation differently in women and men.

BACKGROUND: While aging clearly has protean biological effects on every organ system, the differential effects of aging in women and men in the retrobulbar vasculature, to our knowledge, have never been investigated. Because glaucoma and age-related macular degeneration are closely linked to advanced age, we performed a cross-sectional study using color Doppler imaging of 4 retrobulbar vessels in both healthy women and men. OBJECTIVE: To define the influence of aging per se on ocular hemodynamics. METHODS: Women (n = 73) and men (n = 55), aged from 20 to 90 years, free of ocular and systemic disease, and with normal intraocular pressure, were recruited for this study. Postmenopausal women who were not receiving estrogen replacement therapy were also recruited. Studies involved color Doppler imaging analysis of the ophthalmic, central retinal, and nasal and temporal posterior ciliary arteries. Ophthalmic arterial peak systolic and end-diastolic velocities and a Pourcelot resistance index were determined for each vessel. RESULTS: In both sexes, ophthalmic arterial end-diastolic velocity decreased and the Pourcelot resistance index rose with advancing age (each P<. 001); peak systolic velocity in the ophthalmic vessel was age-independent. In contrast, central retinal arterial flow velocities were unaffected by age in both sexes. In the posterior ciliary arteries, in men, flow velocities and the Pourcelot resistance index were independent of age. However, in women, end-diastolic velocity decreased with age in both the nasal and temporal posterior ciliary vessel (each P<.05); peak systolic velocity was constant; the Pourcelot resistance index in each ciliary artery rose with advancing age (each P<.05). CONCLUSION: In healthy women and men, aging-induced changes in retrobulbar hemodynamics are comparable to alterations seen in patients with glaucoma or age-related macular degeneration, suggesting that vascular changes with senescence may contribute to increased risk for these diseases in older age. Arch Ophthalmol. 2000;118:1076-1080

Adult↗

Endothelin-1-mediated retinal artery vasospasm and the rabbit electroretinogram.

Electroretinogram (ERG) changes invariably accompany the selective interruption of the retinal circulation that occurs in human central retinal artery occlusion. Since arteriolar ligation or ocular hypertension in the rabbit eye is occasionally used to model human central retinal artery occlusion, we conducted the present study to determine whether selective interruption of the retinal circulation of the rabbit eye alters retinal function as measured by the ERG. The vasoconstrictor, endothelin-1, was injected into the vitreous of rabbits' eyes to induce complete vasospasm and selective interruption of the retinal circulation. This procedure was compared to vascular ligation of the ophthalmic and ciliary arteries in which both the retinal and choroidal circulations were interrupted. A total of 8 rabbits was studied. Circulation was monitored angiographically in half of the eyes, and retinal function was monitored by the ERG in the remaining eyes. Endothelin-1 obliterated retinal arteriolar blood flow without affecting choroidal blood flow for at least 1 hr. Although ERG a-wave amplitude showed a small decline over 2 hr, b-wave and oscillatory potential amplitudes (measures of inner retinal function) showed no loss over this period. In contrast, ligation of the ophthalmic and ciliary arteries produced complete obliteration of both retinal arteriolar and choroidal blood flow and complete loss of the ERG after 2 min. Endothelin-1 induces acute, selective interruption of retinal arteriolar blood flow which has no significant physiologic effect on inner retinal function of the rabbit as monitored by the ERG. The avascular rabbit retina appears to be a poor choice for modeling human retinal artery occlusion.

Animals↗

Olestra consumption is not associated with macular pigment optical density in a cross-sectional volunteer sample in Indianapolis.

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.

Adult↗

Intravitreal triamcinolone acetonide in exudative age-related macular degeneration.

PURPOSE: To examine the effects of intravitreal injection of 4.0 mg triamcinolone acetonide on the visual and clinical course of exudative age-related macular degeneration. METHODS: A randomized clinical trial of a single injection of triamcinolone acetonide into the vitreous cavity of experimental eyes at baseline versus observation of untreated subjects was performed in 27 patients followed up for 6 months. Inclusion criteria included exudative age-related macular degeneration with subfoveal or occult choroidal neovascularization, and visual acuity between 20/40 and 20/400. Examination, acuity assessment, fundus photography, and fluorescein angiography were performed at baseline and at 3 and 6 months after enrollment. LogMAR visual acuity was compared between groups by a repeated measures analysis of variance model. Masked assessment of photographic studies was performed and groups were compared with Fisher's exact test. RESULTS: Visual acuity was significantly better in the treated group compared with control subjects at 3 and 6 months (P < 0.005). Fundus photography and angiography were more likely to show stability or improvement at 3 and 6 months in the treated group (P = 0.05). Intraocular pressure elevation was seen in 25% of treated patients, but was controlled with topical medications. Progression of cataract was more frequently seen in the treated group. CONCLUSIONS: Intravitreal triamcinolone acetonide may provide short-term improvement in visual acuity and fundus findings in exudative macular degeneration. These findings must be considered preliminary and should be followed by multicenter, masked, placebo-controlled trials with long-term follow-up.

Aged↗

Comparison of intraocular to plasma HIV-1 viral burden in patients with cytomegalovirus retinitis.

PURPOSE: To determine the relationship between plasma and intraocular human immunodeficiency virus-1 (HIV-1) viral loads in 12 consecutive patients undergoing ganciclovir implant surgery for cytomegalovirus (CMV) retinitis. METHODS: Aqueous and vitreous specimens were assayed for HIV-1 viral load by polymerase chain reaction analysis (Roche Amplicor HIV Monitor; Roche Diagnostics Systems, Inc, Branchburg, New Jersey). RESULTS: It was possible to quantitatively assay HIV-1 burden in intraocular fluids using polymerase chain reaction analysis. In general, patients with plasma viral loads less than 250,000 copies/ml had undetectable (<200 copies/ml) HIV-1 in their aqueous and vitreous. CONCLUSIONS: It is likely that intraocular viral levels have several determinants in addition to plasma viral loads, with which they only partially correlate.

AIDS-Related Opportunistic Infections↗

Mitochondrial maculopathy: geographic atrophy of the macula in the MELAS associated A to G 3243 mitochondrial DNA point mutation.

PURPOSE: To report ocular findings in the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) in a family with the A to G 3243 mitochondrial (mt) DNA point mutation. METHODS: Case reports. Ocular findings are described from four family members with the MELAS associated A to G 3243 mt DNA point mutation. RESULTS: Findings included ophthalmoplegia, neurosensory deafness, reduction of photopic and scotopic electroretinogram b-wave amplitudes, and myopathy, as well as macular retinal pigment epithelial atrophy. No family members had nyctalopia, attenuation of retinal blood vessels, or retinal bone spicule pigmentation. CONCLUSION: The finding of slowly progressive macular retinal pigment epithelial atrophy expands the reported phenotypic diversity of patients with A3243G mt DNA mutations.

Adenine↗

Color Doppler imaging discloses reduced ocular blood flow velocities in nonexudative age-related macular degeneration.

PURPOSE: To study ocular perfusion defects in age-related macular degeneration. METHODS: Twenty-five subjects with nonexudative age-related macular degeneration were compared with 25 age-matched control subjects in studies of flow velocities in several retrobulbar vessels. Color Doppler imaging, which was performed by an examiner who was masked to the subjects' assignment to the control or age-related macular degeneration group, measured peak systolic and end diastolic velocity in the ophthalmic, central retinal, and nasal and temporal posterior ciliary arteries of one eye. A resistive index was calculated from the peak systolic and end diastolic velocity. RESULTS: Subjects with nonexudative age-related macular degeneration showed a consistent trend toward lower peak systolic and end-diastolic velocities in the posterior ciliary arteries. For example, in the nasal posterior ciliary artery, the mean end diastolic velocity measured 1.45 +/- 0.34 cm per sec in the age-related macular degeneration group compared with 1.96 +/- 0.66 cm per sec in the control group, yielding a 26% decrease in the age-related macular degeneration group, which represented the largest difference and was highly statistically significant (P = .0012). The resistive index was not significantly altered in the nasal or temporal posterior ciliary artery. Subjects with nonexudative age-related macular degeneration did not differ from control subjects in peak systolic velocity, end diastolic velocity, or resistive index in the ophthalmic artery. In the central retinal artery, the end diastolic velocity was lower (1.37 +/- 1.95 cm per sec vs 1.95 +/- 0.66 cm per sec), whereas the resistive index was higher (0.83 +/- 0.05 vs 0.76 +/- 0.06 cm per sec), in the age-related macular degeneration group; these results were highly statistically significant (P = .0007 and P < .0001, respectively). CONCLUSIONS: Retrobulbar vascular changes in nonexudative age-related macular degeneration subjects include reduced flow velocities in the nasal and temporal posterior ciliary arteries. The reduced peak systolic velocity, combined with the reduced end diastolic velocity at a constant resistive index, seen in nonexudative age-related macular degeneration, is consistent with reduced bulk flow in these vessels, suggesting that choroidal perfusion is abnormal in this form of age-related macular degeneration. The changes in the central retinal artery suggest there may be a more generalized perfusion abnormality beyond the choroid in patients with age-related macular degeneration or that the central retinal artery exhibits a secondary autoregulatory response to a primary change elsewhere.

Aged↗

Progress in measurement of ocular blood flow and relevance to our understanding of glaucoma and age-related macular degeneration.

New technologies have facilitated the study of the ocular circulation. These modalities and analysis techniques facilitate very precise and comprehensive study of retinal, choroidal, and retrobulbar circulations. These techniques include: 1. Vessel caliber assessment; 2. Scanning laser ophthalmoscopic fluorescein angiography and indocyanine green angiography to image and evaluate the retinal circulation and choroidal circulation respectively; 3. Laser Doppler flowmetry and confocal scanning laser Doppler flowmetry to measure blood flow in the optic nerve head and retinal capillary beds; 4. Ocular pulse measurement; and 5. color Doppler imaging to measure blood flow velocities in the central retinal artery, the ciliary arteries and the ophthalmic artery. These technique have greatly enhanced the ability to quantify ocular perfusion defects in many disorders, including glaucoma and age-related macular degeneration, two of the most prevalent causes of blindness in the industrialized world. Recently it has become clear, in animal models of glaucoma, that retinal ganglion cells die via apoptosis. The factors that initiate apoptosis in these cells remain obscure, but ischemia may play a central role. Patients with either primary open-angle glaucoma or normal-tension glaucoma experience various ocular blood flow deficits. With regard to age-related macular degeneration, the etiology remains unknown although some theories include primary retinal pigment epithelial senescence, genetic defects such as those found in the ABCR gene which is also defective in Stargardt's disease and ocular perfusion abnormalities. As the choriocapillaris supplies the metabolic needs of the retinal pigment epithelium and the outer retina, perfusion defect in the choriocapillaris could account for some of the physiologic and pathologic changes in AMD. Vascular defects have been identified in both nonexudative and exudative AMD patients using new technologies. This paper is a comprehensive update describing modalities available for the measurement of all new ocular blood flow in human and the clinical use.

Animals↗

Ginkgo biloba extract increases ocular blood flow velocity.

We evaluated a possible therapeutic effect of Ginkgo biloba extract (GBE) on glaucoma patients that may benefit from improvements in ocular blood flow. A Phase I cross-over trial of GBE with placebo control in 11 healthy volunteers (8 women, 3 men: Age; 34 +/- 3 years, mean +/- SE) was performed. Patients were treated with either GBE 40 mg or placebo three times daily orally, for 2 days. Color Doppler imaging (Siemens Quantum 2000) was used to measure ocular blood flow before and after treatment. There was a two week washout period between GBE and placebo treatment. Ginkgo biloba extract significantly increased end diastolic velocity (EDV) in the ophthalmic artery (OA) (baseline vs GBE-treatment; 6.5 +/- 0.5 vs 7.7 +/- 0.5 cm/sec, 23% change, p=0.023), with no change seen in placebo (baseline vs GBE-treatment; 7.2 +/- 0.6 vs 7.1 +/- 0.5 cm/sec, 3% change, p=0.892). No side effects related to GBE were found. Ginkgo biloba extract did not alter arterial blood pressure, heart rate, or IOP. Ginkgo biloba extract significantly increased EDV in the OA and deserves further investigation in ocular blood flow and neuroprotection for possible application to the treatment of glaucomatous optic neuropathy as well as other ischemic ocular diseases.

Adult↗

Corticosteroids as an antiangiogenic agent for histoplasmosis-related subfoveal choroidal neovascularization.

The purpose of this study was to evaluate the role of corticosteroids in managing subfoveal choroidal neovascularization (CNV) secondary to the presumed ocular histoplasmosis syndrome. The cases of eighteen patients with histoplasmosis-related subfoveal CNV treated with corticosteroids were reviewed. Ten patients received oral prednisone for 4 to 6 weeks, and eight received a single sub-Tenon's injection of triamcinalone. Visual acuity outcomes were analyzed along with side effect profiles. At two-week follow-up, the prednisone group showed a median improvement in Snellen visual acuity of +2.0 lines, while the triamcinalone group remained essentially stable with a 0.5 line median loss. At treatment end (4 to 6 weeks), both groups showed no significant change in median acuity at 0.0 and -1.0 lines, respectively. Median final vision at 3 months also remained essentially stable at -0.5 lines for each group. Three patients reported anxiety, all of whom were taking prednisone 80 mg daily. Two patients reported increased appetite and weight gain on regimens of prednisone 80 and 100 mg daily. There were no adverse effects reported in the other patients receiving oral prednisone or in any patient receiving sub-Tenon's triamcinalone. The results suggest a beneficial effect of corticosteroids in stabilizing subfoveal CNV secondary to ocular histoplasmosis. In this small series, oral prednisone resulted in a short-term improvement in visual acuity, which stabilized over longer follow-up. The sub-Tenon's triamcinalone group achieved similar final stabilization without the initial improvement. Corticosteroids may be particularly valuable in managing neovascularization in patients who are awaiting interventions currently under development, in preventing recurrence after subfoveal surgery, or in treating non-surgical candidates. Further study is warranted to define the precise role of corticosteroids in this condition.

Administration, Oral↗

Regulation of retinal and optic nerve blood flow.

Blood flow to the retina and optic nerve remains constant over a range of elevated intraocular pressure or mean arterial pressure, independent of sympathetic activation (pressure autoregulation). In addition, increased metabolic activity in these tissues proportionally increases blood flow (metabolic autoregulation). At constant metabolic rate, altered arterial oxygen content reciprocally alters blood flow, leaving total oxygen delivery constant, while blood flow rises and falls with the arterial carbon dioxide tension. These responses are similar to those of the cerebral circulation. However, while aging, atherosclerosis, arterial hypotension, and individual variation may profoundly alter blood flow regulation and predispose to the development of illness, these factors remain largely unexplored.

Animals↗

Evolution of a full-thickness macular hole.

PURPOSE: To illustrate succinctly the various stages of macular hole formation. METHOD: We photodocumented the evolution of a full-thickness macular hole in a patient who refused surgery. RESULTS: A 60-year-old woman, who had had difficulty reading for 3 months, was initially examined with a stage 1B macular hole in her right eye that progressed to stage 2 over a 6-month period and then to stage 3, 2 years after initial examination. CONCLUSIONS: This case demonstrates vividly and succinctly the development of a full-thickness macular hole from stage 1B to stage 3 and provides a unique opportunity to study carefully in a single eye the sequential progression of this important retinal disorder.

Disease Progression↗

The progressive outer retinal necrosis syndrome: successful treatment with combination antiviral therapy.

BACKGROUND AND OBJECTIVE: To assess a two-drug combination of antiviral therapy for the progressive outer retinal necrosis syndrome (PORN), given the current poor outcome with acyclovir alone. PATIENTS AND METHODS: A retrospective review was performed on six consecutive patients who were diagnosed with PORN and were treated with various combinations of intravenous or oral plus intravenous antiviral therapy. The relative efficacies of these modalities were compared. RESULTS: Six eyes of six patients showed active retinitis at the time of presentation. Three patients had unilateral retinitis, and the remaining patients had necrotic, end-stage disease in their fellow eye. All the patients were treated with combination therapy, consisting of either ganciclovir and acyclovir (three patients), foscarnet and ganciclovir (two patients), or foscarnet and acyclovir (one patient). Standard induction doses were employed. During the combination therapy, all six eyes showed resolution of the retinitis, manifested by complete fading of the original retinal lesions and an absence of new lesion formation. At the final follow-up, the areas of prior active retinitis had resolved and remained quiescent. A mild recurrence developed in one eye when ganciclovir and foscarnet were both tapered to a single daily dose. This recurrence promptly resolved with reinduction (twice daily) dosing. Two patients maintained a visual acuity of 20/50 or better in their involved eye for the duration of follow-up (38 and 27 weeks, respectively). One patient maintained a visual acuity of 20/40 for 14 weeks. The remaining three patients had macula-off retinal detachments despite resolution of active retinitis. In addition, for the duration of follow-up, one of the three patients with unilateral disease had retinitis in the uninvolved eye; all three uninvolved fellow eyes maintained a visual acuity of 20/20. One patient had progressive optic atrophy. CONCLUSIONS: Prolonged combination antiviral therapy for PORN may successfully arrest the progression of retinitis, maintain remission, and prevent involvement of the fellow eye. Furthermore, if aggressive therapy is begun early, good vision may be preserved.

AIDS-Related Opportunistic Infections↗