Miyuki Nagahara

Real-Time Measurement of Human Optic Nerve Head and Choroid Circulation, Using the Laser Speckle Phenomenon

A modification of a previously described instrument that used the laser speckle phenomenon for noncontact two-dimensional analysis of the fundus tissue circulation was devised so that tissue circulation in the optic nerve head (ONH) or choroid of the human eye could be measured on a real-time basis. The fundus was illuminated by a diode laser spot and the image speckle was recognized by an area sensor. A quantitative index of blood velocity, normalized blur (NB), was calculated by a logistic board every 0.125 seconds for 7 seconds. Using this modified device, the average NB of the measurement field in the temporal ONH, free of visible surface vessels (NBONH), and that in the posterior choroid (NBch) of normal human eyes were measured. The coefficients of reproducibility of 1-minute interval measurements were 11.7% for the NBONH) and 8.7% for the NBch (each, an average of 5 pulses), and those of 24-hour interval measurements were 13.0% (NBONH) and 9.7% (NBch). The pulsatile component average of NBONH was 38.4% of mean NBONH; of NBch, 26.6% of the mean NBch.

A Placebo-Controlled 3-Year Study of a Calcium Blocker on Visual Field and Ocular Circulation in Glaucoma with Low-Normal Pressure

PURPOSE To study the 3-year effect of oral nilvadipine, a calcium antagonist, on visual field performance and ocular circulation in open-angle glaucoma (OAG) with low-normal intraocular pressure (IOP). DESIGN A randomized, placebo-controlled, double-masked, single-center trial. PARTICIPANTS Patients with OAG who were younger than 65 years and had untreated IOP consistently of 16 mmHg or less. INTERVENTION Oral nilvadipine (2 mg twice daily) or placebo was assigned randomly to patients fulfilling the criteria by the minimization method of balancing the groups according to age, refraction, and the mean deviation (MD) value (Humphrey Perimeter 30-2 SITA Standard Program; Humphrey Instruments, Inc., San Leandro, CA) of the eye with less negative MD. No topical ocular hypotensive drugs were prescribed. Visual field testing was performed every 3 months; fundus examination and IOP, blood pressure, and pulse rate measurements were carried out every month; and quantitative indexes of circulation in the optic disc rim (NB(ONH)) and choroid in the foveal area (NB(fovea)) were determined using the laser speckle method at 0, 3, 6, 12, 18, 24, 30, and 36 months. MAIN OUTCOME MEASURES The time courses of MD, NB(ONH), and NB(fovea) in the eye with less negative MD. RESULTS Thirty-three patients were enrolled; 17 were assigned to nilvadipine and 16 were assigned to placebo; 13 in each group completed the study. No significant intergroup difference was seen in age, refraction, or baseline values of any of the parameters. During the 3-year period, the IOP averaged 12.6 mmHg in the nilvadipine group and 12.8 mmHg in the placebo group (P>0.1), and no significant change from baseline or intergroup difference was seen in blood pressure or pulse rate. The estimated slope of change in the MD was less negative in the nilvadipine than in the placebo group (-0.01 vs. -0.27 decibels/year; P = 0.040). The NB(ONH) and NB(fovea) values remained increased compared with baseline for the study period by approximately 30% to 40% only in the nilvadipine group, and the intergroup difference was significant (P = 0.003 for NB(ONH) and P = 0.007 for NB(fovea)). CONCLUSIONS Nilvadipine (2 mg twice daily) slightly slowed the visual field progression and maintained the optic disc rim, and the posterior choroidal circulation increased over 3 years in patients with OAG with low-normal IOP.

In vivo measurement of blood velocity in human major retinal vessels using the laser speckle method.

PURPOSE To develop a simple, noninvasive method of determining blood velocity and flow through human retinal vessels (RVs), by using the laser speckle method and validating the results by bidirectional laser Doppler velocimetry (LDV). METHOD The square blur rate (SBR), a quantitative blurring index of the laser speckle pattern that parallels the velocity of moving substances, obtained from blood flowing through glass capillary tubes (RV analogues), correlated with tube diameter, background reflectance and absorption, flow velocity, and the SBR obtained from blood flowing through underlying glass capillary tubes (choroidal vessel analogues). A nomogram was constructed to calculate the blood velocity in human RVs from the SBR values obtained in vivo. Blood velocities in RVs were determined in 12 normal eyes by using the laser speckle method and bidirectional LDV. Measurements were performed twice at the same site at 1-hour intervals. RESULTS Measurements from a temporal superior artery (n = 12; mean ± SD) were blood velocity (V(mean)), 41.7 ± 4.2 mm/s; flow, 13.0 ± 3.2 μL/min; and diameter, 119.5 ±15.7 μm and time to complete one measurement, 65 ± 18 seconds, with the laser speckle apparatus; and V(mean), 37.7 ± 6.7 mm/s; flow, 11.7 ±3.0 μL/min; diameter, 111.1 ±16.6 μm; and measurement time, 112 ± 25 seconds, with the bidirectional LDV apparatus. The results obtained by the two methods correlated with each other (V(mean), r = 0.59, P = 0.023; flow, r = 0.83, P = 0.005; and diameter, r = 0.56, P = 0.032). The coefficients of reproducibility for V(mean), blood flow, and diameter measurement were 9.5% ± 2.5%, 10.5% ± 3.2%, and 5.3% ± 2.7% for the former and 15.3% ± 4.2%, 18.5% ± 4.1%, and 6.2% ± 2.2% for the latter, respectively. CONCLUSIONS The laser speckle method accurately and reproducibly determines blood velocity in human RVs in less time than the LDV apparatus requires.

Relation between retrobulbar circulation and progression of diabetic retinopathy

Aims: To investigate retrobulbar circulatory parameters in type 2 diabetic patients with and without diabetic retinopathy (DR) progression. Methods: This was a prospective cohort study. One eye of 35 diabetic patients with background DR (BDR) were included in the study. Eyes without DR, with proliferative DR, photocoagulation, past surgical procedures, or other ophthalmic disease except BDR and cataract were excluded. The study was masked. Colour Doppler imaging (CDI) was used to measure the retrobulbar circulation at the beginning of the study and after a mean follow up interval of 21 months. Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistivity index (RI) in the central retinal artery and vein and the posterior ciliary artery were measured. Results: 18 patients who developed DR progression showed significantly increased central retinal vein PSV ( 5.6 (3.5–9.1) p = 0.003), EDV ( 3.4 (2.3–4.4) p = 0.04), and RI ( 0.43 (0.20–0.56) p = 0.02) at the final measurement compared to the initial measurement (PSV = 4.6 (3.2–7.0); EDV = 3.0 (2.3–3.7); RI = 0.40 (0.17–0.52)). Circulatory parameters in the central retinal artery and the posterior ciliary artery did not alter significantly after progression of DR. 17 patients were without DR progression and they did not show any significant differences in the measured circulatory parameters on entry compared to the final measurement. Conclusion: The authors suggest that the initial changes in the retrobulbar circulation during DR progression occur in the central retinal vein.

Topical Latanoprost and Optic Nerve Head and Retinal Circulation in Humans

The purpose of the present study was to study the effect of a single instillation of latanoprost on the human optic nerve head (ONH) and retinal circulation. Using laser-speckle tissue blood flow analysis, normalized blur (NB; a quantitative index of tissue blood velocity) was measured every 0.125 sec at a temporal ONH site free of visible surface vessels. Measurements were averaged for 3 cardiac cycles (NB(ONH)). Color Doppler Imaging (CDI) was also used to evaluate peak systolic blood velocity (PSV), endo-diastolic velocity (EDV), and resistive index (RI) in the central retinal artery (CRA) and mean blood velocity (MV) in the central retinal vein (CRV). One drop of 0.005% latanoprost was instilled into one eye and its vehicle into the other in eleven healthy volunteers in a double-blinded manner. Measurements of bilateral NB(ONH), CDI parameters, intraocular pressure (IOP), blood pressure (BP), and pulse rate (PR) were performed before, and 45, 90, 180, and 270 min after instillation. After a single instillation of latanoprost or the vehicle, there was no significant bilateral difference throughout the experimental period. The difference in NB(ONH) between that before and at each time point of measurement (delta NB(ONH)) in the latanoprost-treated eyes was significantly higher between 45 and 270 min after instillation than that in vehicle-treated eyes (P = 0.0003 to 0.0156); ANOVA for repeated measurements also revealed significant difference between both eyes (P < 0.00001). BP, PR, and NB(ONH) in the eye that received only the vehicle, PSV, EDV, and RI in the CRA in both eyes, and MV in the CRV in both eyes changed little. Tissue blood velocity in the ONH increased at least temporarily following a single instillation of topical latanoprost. Although the mechanism of the increase is unclear, the effects of latanoprost on ONH tissue circulation in humans may have clinical implications.

Effects of scleral buckling and encircling procedures on human optic nerve head and retinochoroidal circulation

AIMS To study the effects of segmental scleral buckling and encircling procedures on tissue circulation in the human optic nerve head (ONH) and choroid and retina. METHODS Using the laser speckle method, the normalised blur (NB) value, a quantitative index of tissue blood velocity, was measured every 0.125 seconds and averaged over three pulses in the optic nerve head (NBONH) and choroid and retina (NBch-ret) in 10 patients with unilateral rhegmatogenous retinal detachment (mean age 52 (SD 17)). NBONH, NBch-ret, and intraocular pressure (IOP) in both eyes, and blood pressure (BP) were measured before, and 1, 4, and 12 weeks after the scleral buckling and encircling procedure. RESULTS NBch-reton the buckled side was significantly reduced after surgery and smaller than that in the unoperated contralateral eye throughout the study period (ANOVA, p<0.0001). NBch-ret on the unbuckled side, in the foveal area, NBONH, IOP, and BP showed no significant change. CONCLUSIONS It was indicated that the segmental scleral buckling procedure with encircling elements decreased tissue blood velocity in the choroid and retina on the buckled side but caused no significant change on tissue circulation in other areas of the fundus or ONH.

Spontaneous posterior dislocation of intraocular lenses fixated in the capsular bag

We report 4 cases of complete posterior dislocation of an intraocular lens (IOL) in the capsular bag occurring a mean of 5.5 years after uneventful cataract surgery. In all 4 cases, posterior chamber IOLs were fixated within the capsulorhexis. The patients experienced sudden loss of vision without an episode of trauma or ocular disease. Using a 3-port pars plana vitrectomy, the IOLs were explanted through a limbal incision and a new IOL was sutured to the ciliary sulcus. Histological examination indicated that zonular fibers were severed at the site of insertion in the capsule.

Acute effects of cigarette smoking on tissue circulation in human optic nerve head and choroid-retina.

OBJECTIVE To study the acute effects of cigarette smoking on tissue circulation in the human optic nerve head (ONH) and choroid-retina. DESIGN Nonrandomized, comparative trial (sequential self-controlled). PARTICIPANTS Nine healthy habitual smokers (age, 28 +/- 4 years; number of cigarettes smoked per day, 27 +/- 10; length of smoking history, 10 +/- 4 years; mean +/- standard deviation). INTERVENTION Using the laser speckle method, normalized blur (NB) value, a quantitative index of tissue blood velocity, was measured every 0.125 second and averaged over three pulses across an area located in the temporal site of the ONH free of visible surface vessels (NB(ONH)) and across an area located halfway between the macula and the ONH with no discrete vessels visible (NB(ch-ret)). NB(ONH), NB(ch-ret), and intraocular pressure (IOP) in one randomly chosen eye, and blood pressure (BP) and pulse rate (PR) were measured before and 1, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minutes after sham smoking using a short drinking straw as a cigarette substitute (control). One week later, NB(ONH), NB(ch-ret), and IOP in the same eye, and BP and PR were measured after cigarette smoking according to the same time schedule as in the control experiment. MAIN OUTCOME MEASURES NB(ONH) and NB(ch-ret). RESULTS In the control experiment, all parameters examined showed no significant change during the experimental period. Differences in NB(ONH) and NB(ch-ret) before and after actual smoking were significantly greater than those in the control experiment (analysis of variance, P = 0.0000, 0.0000). BP and PR were significantly increased between 1 and 30 minutes after actual smoking as compared with control data, while IOP showed no significant change at any time of measurement. CONCLUSIONS These results indicated that cigarette smoking increased tissue blood velocity in the ONH and possibly in the choroid in habitual smokers.

Retrobulbar circulation in myopic patients with or without myopic choroidal neovascularisation.

Aim: To investigate the effect of myopia and myopic choroidal neovascularisation (CNV) on retrobulbar circulation in central retinal artery (CRA) and vein (CRV) and posterior ciliary artery (PCA). Methods: 52 subjects with and without myopia were included in the study. Retrobulbar circulation was measured using colour Doppler imaging. Analysis of correlation of degree of myopia with blood flow velocity parameters was done. Circulatory differences between eyes of patients with unilateral neovascular degenerative myopia were estimated. Results: The analysis of correlation between dioptry and blood flow velocity in the CRA, CRV, and PCA showed a significant positive correlation. Axial length was also significantly correlated with CRA and CRV blood velocity and had a tendency to be correlated with PCA blood velocity. When compared with the fellow eye, the eye with myopic CNV had significantly higher resistivity index (RI) (p=0.048) in the PCA and no significant difference in the circulatory parameters of the CRA and CRV. Conclusion: Central retinal and posterior ciliary blood velocity decreases with the increase of the degree of myopia. PCA RI is higher in myopic CNV.

Optic nerve head circulation after intraocular pressure reduction achieved by trabeculectomy

OBJECTIVE To study the effects of trabeculectomy and needling revision of poorly functioning blebs on the optic nerve head (ONH) circulation in patients with primary open-angle glaucoma (POAG). DESIGN Prospective, nonrandomized, self-controlled trial. PARTICIPANTS Nineteen POAG patients (age range, 52 +/- 12 years; mean +/- standard deviation) undergoing trabeculectomy and six POAG patients (age range, 62 +/- 14 years) undergoing needling revision of the bleb. METHODS Using the laser speckle method, the normalized blur (NB) value, a quantitative index of blood velocity, was determined every 0.125 seconds and averaged more than three cardiac pulses in the optic nerve head (NB(ONH)). MAIN OUTCOME MEASURES The NB(ONH) and intraocular pressure (IOP) in both eyes, and blood pressure (BP) and pulse rate (PR) were measured before and 2 days and 1, 4, and 8 weeks after trabeculectomy, and also before and 10 and 40 min after needling procedures. RESULTS Intraocular pressure in the operated eye was significantly decreased after trabeculectomy or needling procedures, and the ocular perfusion pressure was significantly increased by a maximum of 38%. The IOP in the unoperated eye, BP, and PR did not significantly change. The NB(ONH) did not significantly change in either the operated or unoperated eye. CONCLUSIONS Trabeculectomy and needling procedures induced little change in the ONH circulation.