Effect of aging on macular features of X-linked retinoschisis assessed with optical coherence tomography.

PURPOSE: X-linked retinoschisis (XLRS) is one of the most common causes of macular degeneration in young men. The purpose of this study was to use optical coherence tomography combined with ophthalmoscopy to study the effects of aging on the morphologic changes associated with XLRS. METHODS: Twenty-five eyes of 17 men with XLRS ranging in age from 3 years to 68 years were studied using ophthalmoscopy and optical coherence tomography. Optical coherence tomography was used to measure macular thickness and to evaluate XLRS-related structural changes. Correlation analyses between the findings and patients' age and visual acuity were performed. RESULTS: Mean visual acuity was 20/100 (range, 20/40 to 20/400). There were no correlations between visual acuity and age or macular thickness. However, there was a significant decrease in macular thickness with age (P < 0.01). Eyes with posterior vitreous detachment had significantly decreased central foveal thickness (P < 0.001). Various retinal morphologic changes could be identified by optical coherence tomography, including epiretinal membranes, intraretinal cysts, tissue pillars bridging the schisis cavities, and tissue hyperreflectivity in collapsed XLRS. These findings were significantly correlated with age. CONCLUSION: Optical coherence tomography revealed various retinal morphologic changes associated with XLRS. These changes were correlated with age but not with visual acuity. Younger patients showed cystic retinal elevation, whereas older patients showed collapsed retinoschisis with retinal thinning.

Ophthalmologic techniques to assess the severity of hyperviscosity syndrome and the effect of plasmapheresis in patients with Waldenström's macroglobulinemia.

BACKGROUND: The aim of this study is to determine the serum immunoglobulin (Ig) M and serum viscosity (SV) levels at which retinal changes associated with hyperviscosity syndrome (HVS) as a result of Waldenström's macroglobulinemia (WM) occur. In addition, the effect of plasmapheresis on HVS-related retinopathy was tested. PATIENTS AND METHODS: A total of 46 patients with WM received indirect ophthalmoscopy, laser Doppler retinal blood flow measurements, serum IgM, and SV determinations. A total of 9 patients with HVS were studied before and after plasmapheresis. RESULTS: Mean IgM and SV levels of patients with the earliest retinal changes were 5442 mg/dL and 3.1 cp, respectively. Plasmapheresis improved retinopathy, decreased serum IgM (46.5 +/- 18%; P = .0009), SV (44.7 +/- 17.3%; P = .002), retinal venous diameter (15.3 +/- 5.8%; P = .0001), and increased venous blood speed by +55.2 +/- 22.5% (P = .0004). CONCLUSION: Examination of the retina is useful in identifying the symptomatic threshold of plasma viscosity levels in patients with HVS and can be used to gauge the effectiveness of plasmapheresis treatment.

Evaluation of macular abnormalities in Stargardt's disease using optical coherence tomography and scanning laser ophthalmoscope microperimetry.

BACKGROUND: The purpose of this study is to evaluate the diagnostic value of optical coherence tomography (Stratus OCT) and scanning laser ophthalmoscope (SLO) microperimetry in patients with Stargardt's disease (STGD), and the correlation between macular morphology and visual function in these patients. METHODS: Twenty-two patients with STGD (mean age 44 years, range 11 to 71 years) and 20 age-matched healthy control subjects were included in the study. OCT imaging was performed using six radial line scans manually centered on the fovea. SLO microperimetry was used to assess central scotoma and fixation behavior in patients with STGD. RESULTS: Mean best corrected Snellen visual acuity (BCVA) was 20/80, range 20/25 to 20/300 (log MAR 0.6, range 0.1 to 1.2) in the STGD group and 20/20 (log MAR 0.0) in the control group. Foveal thickness was significantly reduced in patients with STGD (119.0 +/- 19.6 microm) compared to controls (210.7 +/- 19.6 microm, P < 0.0001). A significant correlation between foveal thickness and BCVA was observed within the STGD group (R(2) = 0.62, P < 0.0001). Photoreceptor loss in the macular area and a corresponding central scotoma were observed in all STGD patients. CONCLUSIONS: OCT findings, particularly reduced foveomacular thickness and photoreceptor loss in the macular area may be useful in the diagnosis of STGD. Furthermore, a strong correlation between foveal thickness and visual function was observed in our patients. Assessment of central visual function using SLO microperimetry provides additional useful information, important in the management of STGD.

Effect of plasmapheresis on hyperviscosity-related retinopathy and retinal hemodynamics in patients with Waldenstrom's macroglobulinemia.

PURPOSE: Waldenström's macroglobulinemia (WM) is characterized by an overproduction of immunoglobulin M (IgM), which can lead to a hyperviscosity syndrome (HVS) and HVS-related retinopathy. Plasmapheresis is known to reduce serum viscosity (SV) and IgM levels. The purpose of this study was to investigate the effects of plasmapheresis on HVS-related retinopathy and retinal hemodynamic parameters in patients with WM. METHODS: Nine patients with HVS due to WM were studied. SV and plasma IgM levels were measured before and after plasmapheresis treatment. The patients were evaluated for HVS-related retinopathy, and hemodynamic changes in a major temporal retinal vein by laser Doppler, before and after plasmapheresis. RESULTS: Plasmapheresis resulted in significant reductions in serum IgM (46.5% +/- 18.0%, mean +/- SD; P = 0.0009) and SV (44.7% +/- 17.3%, P = 0.002). HVS-related retinopathy improved in all patients after plasmapheresis. After treatment, the venous diameter decreased in each patient by an average of 15.3% +/- 5.8% (P = 0.0001). A significant (P = 0.0004) 55.2% +/- 22.5% increase in retinal venous blood speed accompanied the decreases in diameter. There was no significant change in the retinal blood flow rate after treatment. The percentage decreases in SV in the patients were significantly correlated with the percentage decreases in venous blood column diameter (P = 0.031, R(2) = 0.51). CONCLUSIONS: HVS triggers a distinctive retinopathy with a central retinal vein occlusion (CRVO)-like appearance. However, the retinal blood flow is not decreased as in CRVO, but remains at normal levels. Plasmapheresis is effective in reversing HVS-related retinopathy and in reducing abnormal venous dilatation.

Retinal blood flow response to posture change in glaucoma patients compared with healthy subjects.

PURPOSE: To characterize the retinal vascular autoregulatory response to ocular perfusion pressure (OPP) changes in patients with glaucoma and in healthy control subjects. DESIGN: Observational cohort study. PARTICIPANTS: Eighteen patients with open-angle glaucoma (OAG) and 8 control subjects, all females ages 40 to 60 years, were studied. Only subjects with known maximum intraocular pressure less than 22 mmHg in both eyes were included. METHODS: Arterial diameter and blood speed in the inferior temporal retinal artery of the left eye were measured simultaneously at baseline while sitting, while reclining for approximately 30 minutes, and once again sitting using a retinal laser Doppler instrument. Blood flow rate was computed automatically. Brachial artery blood pressure and heart rate also were measured. MAIN OUTCOME MEASURE: Change in blood flow rate while reclining for approximately 30 minutes compared with baseline blood flow rate measured while seated. RESULTS: In control subjects, arterial diameter decreased by 7.5+/-3.4% (P = 0.0003) and blood speed increased by 24.6+/-10.8% (P = 0.004) while reclining compared with baseline. The concomitant change in the blood flow rate (6.5+/-12.0%; P = 0.15) compared with baseline was not statistically significant. In contrast, OAG patients showed a much broader range of blood flow changes in response to posture change (14.9+/-37.7%; P = 0.086) compared with baseline. Although there were no significant differences in the flow changes compared with baseline in either group, there was a significant difference in the variance of the blood flow changes in the OAG patients compared with the controls (P = 0.0025). Division of the OAG patients into subgroups revealed a significant (P = 0.031) association between baseline OPP and the retinal blood flow response to posture change. CONCLUSIONS: The authors describe the hemodynamic details of retinal vascular autoregulation in response to posture-induced changes in OPP in healthy subjects and document the lack of such autoregulation in a selected group of patients with OAG.

Retinal blood flow and nerve fiber layer measurements in early-stage open-angle glaucoma.

PURPOSE: To evaluate the relationship between retinal circulatory abnormalities and retinal nerve fiber layer (RNFL) thinning in early-stage open-angle glaucoma (OAG) to help elucidate the mechanisms underlying the development of glaucomatous optic neuropathy. DESIGN: Prospective cross-sectional. METHODS: Twelve patients with early OAG and a known maximum untreated intraocular pressure less than 22 mm Hg (age, 61.4 +/- 9.7 years; Humphrey visual field mean deviation -2.7 +/- 2.1) and eight age-matched healthy control subjects (age, 58.5 +/- 8.3 years) were included in the study. Blood column diameter, centerline blood speed, and retinal blood flow were measured in the major inferior temporal retinal artery using a Canon laser Doppler blood flow instrument (CLBF 100; Canon, Tokyo, Japan). Peripapillary RNFL thickness was measured using a Stratus optical coherence tomography instrument. RESULTS: On average, there were significant reductions in retinal blood speed (P = .009) and flow (P = .010) in OAG patients compared to controls. The RNFL was significantly thinner in the OAG patients compared to controls (P = .002). There were significant inverse correlations between retinal blood flow and average RNFL thickness and RNFL thickness in the inferior quadrant within the glaucoma group (Rsq = 0.50, P = .01; Rsq = 0.62, P = .003). CONCLUSION: The results showed that a thinner RNFL was associated with a higher retinal blood flow in patients with early-stage OAG. The mechanisms underlying this phenomenon remain to be elucidated.

Retinal abnormalities in early Alzheimer's disease.

PURPOSE: There is evidence suggesting that visual disturbances in patients with Alzheimer's Disease (AD) are due to pathologic changes in the retina and optic nerve, as well as to higher cortical impairment. The purpose of this study was to evaluate retinal hemodynamic parameters and to characterize patterns of retinal nerve fiber layer (RNFL) loss in patients with early AD. METHODS: Nine patients with mild to moderate probable AD (mean Mini Mental State Examination score 24 of a possible 30 (age 74.3 +/- 3.3 years; mean +/- SD) and eight age-matched control subjects (age, 74.3 +/- 5.8 years) were included in this prospective cross-sectional study. Blood column diameter, blood velocity, and blood flow rate were measured in the major superior temporal retinal vein in each subject by using a laser Doppler instrument. Peripapillary RNFL was measured by optical coherence tomography. RESULTS: Patients with AD showed a significant narrowing of the venous blood column diameter (131.7 +/- 10.8 microm) compared with control subjects (148.3 +/- 12.7 microm, P = 0.01), and a significantly reduced venous blood flow rate (9.7 +/- 3.1 microL/min) compared with the control subjects (15.9 +/- 3.7 microL/min, P = 0.002). A significant thinning of the RNFL was found in the superior quadrant in patients with AD (92.2 +/- 21.6 microm) compared with control subjects (113.6 +/- 10.7 microm, P = 0.02). There were no significant differences in the inferior, temporal, or nasal RNFL thicknesses between the groups. CONCLUSIONS: Retinal abnormalities in early AD include a specific pattern of RNFL loss, narrow veins, and decreased retinal blood flow in these veins. The results show that AD produces quantifiable abnormalities in the retina.

Hyperviscosity-related retinopathy in waldenstrom macroglobulinemia.

OBJECTIVES: To determine the earliest retinal changes associated with Waldenström macroglobulinemia (WM) and to ascertain the serum IgM and serum viscosity (SV) levels at which these changes occur. METHODS: Patients with WM were evaluated using indirect ophthalmoscopy with scleral depression, laser Doppler retinal blood flow measurements, and serum IgM and SV determinations. Hemodynamic findings were compared with those of a group of age-matched controls. A retinopathy severity scale was developed, and the associated IgM and SV values were related to particular morphologic changes. RESULTS: A total of 46 patients with WM and 14 age-matched, healthy controls participated in the study. Patients exhibited far-peripheral hemorrhages and venous dilation with increasing SV and IgM values. Central retinal changes were associated with significantly higher SV values. Retinal vessel diameter increased with increasing serum IgM and SV levels. The mean IgM level of patients with the earliest retinal changes was 5442 mg/dL. The mean SV level was 3.1 cP. CONCLUSIONS: Retinal manifestations of hyperviscosity syndrome occur at lower serum IgM and SV levels than previously reported. Indirect ophthalmoscopy with scleral depression along with retinal vessel diameter measurements are able to detect the earliest hyperviscosity syndrome-related complications and should be considered in the treatment of patients with WM.

Defective Myogenic Response of Retinal Vessels Is Associated With Accelerated Onset of Retinopathy in Type 1 Diabetic Individuals.

PURPOSE: We seek to identify pathogenic mechanisms for diabetic retinopathy that can become therapeutic targets beyond hyperglycemia and hypertension. We investigated if a defective myogenic response of retinal arteries to increased perfusion pressure, which exposes capillaries to increased pressure and flow, is associated with the onset of clinical retinopathy. METHODS: We examined prospectively the incidence of retinopathy in type 1 diabetic individuals tested 4 years earlier for the retinal arterial myogenic response, and in a cross-sectional study the prevalence of defective myogenic response in type 1 patients who had diabetic retinopathy. Among these, we contrasted early-onset (after 15 ± 2 years of diabetes, E-DR; n = 5) to late-onset (after 26 ± 3 years of diabetes, L-DR; n = 7) retinopathy. We measured the myogenic response using a laser Doppler blood flowmeter after a change in posture from sitting to reclining, which increases retinal perfusion pressure. RESULTS: Five of seven participants who 4 years prior had a defective myogenic response had now developed clinical retinopathy; as compared with only one of six participants who 4 years prior had a normal response (P = 0.10). In the cross-sectional study, all participants had normal retinal hemodynamics at steady state. In response to the postural change, only the E-DR group showed defective myogenic response (P = 0.005 versus controls, P = 0.02 versus L-DR) and abnormally high retinal blood flow (P = 0.016 versus controls). CONCLUSIONS: In type 1 diabetic patients, a defective myogenic response of retinal arteries to pressure is not required for the development of clinical retinopathy, but is prominently associated with an accelerated onset of retinopathy.

OCT measurements in patients with optic disc edema.

PURPOSE: This study investigated the influence of disc edema (DE) caused by inflammatory optic neuropathies or retinal vein occlusions on optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness measurements. METHODS: OCT RNFL circle scans centered on the optic disc were made for 13 patients with DE (7 with retinal vein occlusions and 6 with inflammatory optic neuropathies) and 13 controls. RNFL thickness was assessed using the OCT normative database. The same circle scans were also used for peripapillary total retinal thickness measurements. The RNFL percentage of total retinal thickness was calculated, normalized (nRNFL%), and averaged separately for affected and unaffected regions of each eye. RESULTS: Average RNFL thickness was 122 +/- 23 microm in the DE group, and 91 +/- 8 microm in the control group (P = 0.0001). Mean peripapillary total retinal thickness was 329 +/- 56 microm in the DE group and 255 +/- 12 microm in the control group (P < 0.001). Comparison of the averaged nRNFL% values at measurement locations above the range of the normative database with averaged nRNFL% values at measurement locations within the range of the normative database in the optic neuropathy group showed a significant difference (P = 0.024); however, the same analysis in the retinal vein occlusion group revealed no significant difference. CONCLUSIONS: OCT measurements are influenced by DE and show significantly greater thickness values in those patients than in controls. The presence of a significant difference within the averaged nRNFL% values in the optic neuropathy group and the absence of such a difference in the retinal vein occlusion group could be explained by edema primarily affecting the RNFL in optic neuropathy in contrast to what occurs in retinal vein occlusion, where edema affects all retinal layers.

Assessment of the effects of morphological changes related to age-related macular degeneration on optical coherence tomography retinal thickness measurements.

BACKGROUND AND OBJECTIVE: Age-related macular degeneration (AMD) leads to morphological changes that can interfere with optical coherence tomography retinal thickness measurements. The effects of AMD on two available retinal thickness scan modes were tested. PATIENTS AND METHODS: Ninety-four scans, equally divided into Radial Line Scans (RLS) and Fast Macula Scans (FMS), of 42 patients with AMD were reviewed. Patients were graded into 4 categories regarding AMD severity. Each scan mode was evaluated for each AMD category. RESULTS: In dry moderate AMD, 2% of the RLS and 5% of the FMS thickness measurements failed. In dry progressed AMD, the RLS mode performed better (26% failure rate) than the FMS mode (42% failure rate). However, in exudative AMD the FMS mode performed better (6% failure rate) than the RLS mode (28% failure rate). The difference between the RLS and FMS performance in dry progressed AMD compared with exudative AMD was significant (P < .0001). CONCLUSION: The optical coherence tomography retinal thickness scan modes perform differently, depending on AMD severity. Retinal thickness algorithms with better performance are needed to facilitate measurements in patients with AMD.

Retinal blood flow in mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Patients with Alzheimer's disease (AD) demonstrate the narrowing of retinal veins and decreased retinal venous blood flow compared with control subjects. We assessed whether these abnormalities are present in patients with mild cognitive impairment (MCI). METHODS: After the determination of the global clinical dementia rating, 52 subjects (10 AD, 21 MCI, and 21 normal controls) underwent retinal hemodynamic profiling. Blood column diameter, blood speed, and blood flow were measured in a major temporal retinal vein using retinal laser Doppler flowmetry. In addition, peripapillary retinal nerve fiber layer (RNFL) thickness was measured using optical coherence tomography. RESULTS: Blood column diameter in AD was narrower than in both MCI (P = .004) and controls (P = .002). However, blood speed in both AD (P = .024) and MCI (P = .005) was lower than in controls. As a result, the differences in blood flow between AD and MCI (P = .036), AD and controls (P < .0001), and MCI and controls (P = .009) were significant. Although there were no differences in RNFL thickness among the groups, blood flow was correlated (P = .047) with superior RNFL thickness in the AD group, but not in the MCI (P = .40) or control (P = .84) groups. CONCLUSIONS: Retinal blood flow in MCI is intermediate between what is measured in control subjects and in AD patients. Our findings suggest that blood flow abnormalities may precede the neurodegeneration in AD.

Optic nerve head circulation in nonarteritic anterior ischemic optic neuropathy and optic neuritis.

PURPOSE: To quantify optic nerve head circulatory abnormalities in patients with unilateral nonarteritic anterior ischemic optic neuropathy (NAION) or optic neuritis (ON), and to assess the potential of such measurements to differentiate NAION from ON. DESIGN: Prospective, cross-sectional, observational study. PARTICIPANTS: Thirty consecutive patients with unilateral NAION, 22 consecutive patients with unilateral ON, and 50 healthy control subjects. METHODS: All subjects underwent a complete neuro-ophthalmologic evaluation. The widths of Doppler-broadened frequency spectra, which are directly proportional to the speed of blood cells flowing through the capillaries of the optic nerve head, were measured at multiple sites in both eyes of each subject. The variation of Doppler broadening (DB) with age was determined in the control subjects. Doppler broadening values in the patients were compared between similar sites in affected and contralateral eyes, and between both affected and contralateral eyes and the age-adjusted values determined in the control subjects. MAIN OUTCOME MEASURES: The differences in DB between (1) the affected and contralateral eyes of the patients, (2) the patients and the control subjects, and (3) the patients with NAION and those with ON. RESULTS: In NAION, DB was decreased at both temporal (-20.2% and -18.5%) and nasal (-12.8% and -12.4%) sites of the nerve head in affected eyes compared with contralateral eyes or eyes of control subjects. In ON, DB was also decreased at temporal sites (-11.3% and -9.2%) in affected eyes compared with contralateral or control eyes. At nasal sites, there were no significant differences in DB in affected eyes of ON patients compared with contralateral or control eyes. The DB decreases were significantly greater in NAION patients than in ON patients. CONCLUSIONS: Optic nerve head circulatory abnormalities are present in patients with NAION or ON. This is the first demonstration of such abnormalities in ON, a finding consistent with the recent attention given to the phenomenon of axonal loss in this disease. Although there are differences in the circulatory abnormalities between the 2 diseases that provide insights into the pathophysiological mechanisms at play, they are not large enough to enable the clinician to distinguish between ON and NAION in an individual patient.

Reproducibility and clinical application of a newly developed stabilized retinal laser Doppler instrument.

PURPOSE: To describe a newly developed stabilized retinal laser Doppler instrument, to report the reproducibility of retinal blood flow measurements, and to present examples of its clinical application. DESIGN: Experimental study. METHODS: The intrasession, intersession, and interobserver reproducibility of retinal blood flow measurements obtained using the Canon Laser Blood Flowmeter model CLBF 100 was assessed. Intrasession: the coefficients of variation (CV) for repeated measurements (5X) of retinal vessel diameter (D), time-average centerline blood velocity (V(av)), and blood flow (F) were calculated at 18 sites along temporal retinal arteries and 18 sites along temporal retinal veins using both eyes in six healthy volunteers. Intersession: the correlation coefficients and average differences between two sets of measurements at the same 36 retinal sites made by one examiner on two different days were calculated. Interobserver: the correlation coefficients and average differences between two sets of measurements at nine sites (five arterial and four venous) in five eyes of five of the volunteers made by two examiners on the same day were calculated. Results from two patients, one with branch retinal vein occlusion (BRVO), and one with central retinal vein occlusion (CRVO), are used to illustrate abnormal retinal circulatory characteristics. RESULTS: intrasession: CV (mean +/- SD) for D, V(av), and F were 5.5% +/- 2.2%, 13.1% +/- 6.3%, and 13.8% +/- 4.7% in arteries and 3.5% +/- 2.1%, 11.9% +/- 5.9%, and 12.7% +/- 5.5% in veins. Intersession/interobserver: strong correlations between measurements made by one examiner on two different days and by two examiners on the same day were found in D, V(av), and F. Average differences in F were 16.4% +/- 12.8% for intersession and 12.6% +/- 7.0% for interobserver comparisons. Results from the patient with BRVO show marked differences in flow characteristics in the affected quadrant compared with an unaffected quadrant in the same eye, and to the fellow eye. Results from the patient with CRVO show a dramatic improvement in flow characteristics after clearing of the occlusion. CONCLUSIONS: The reproducibility results and the fact that blood flow is measured in actual units of microl/min indicate that the instrument can be used for reliable comparison of blood flow characteristics at different retinal vascular sites in the same eye, at comparable sites in both eyes, and for comparison between patients and healthy control subjects.

Effect of brimonidine on retinal vascular autoregulation and short-term visual function in normal tension glaucoma.

PURPOSE: To assess whether brimonidine 0.15% alters retinal vascular autoregulation and short-term visual function in normal tension glaucoma patients who demonstrate retinal vascular dysregulation. DESIGN: Nonrandomized clinical trial. METHODS: In this prospective study, 46 normal tension glaucoma patients not previously treated with brimonidine underwent retinal vascular autoregulation testing and visual function assessment using frequency doubling technology perimetry and equivalent noise motion sensitivity testing. We measured blood flow in a major temporal retinal artery with subjects seated and then while reclined for 30 minutes. Patients having a change in retinal blood flow with posture change outside the range previously found in healthy subjects were classified as having retinal vascular dysregulation. They were treated with brimonidine 0.15% for 8 weeks and designated for retesting. RESULTS: Twenty-three patients demonstrated retinal vascular dysregulation at the initial visit. Younger age (P = .050) and diabetes (P = .055) were marginally significant risk factors for retinal vascular dysregulation. After the 8-week course with brimonidine, 14 of the 17 patients who completed the study showed a return of posture-induced retinal blood flow changes to levels consistent with normal retinal vascular autoregulation (P < .0001). We found no significant changes in frequency doubling technology perimetry or in motion detection parameters following treatment with brimondine (P > .09 for all tests performed). CONCLUSIONS: Brimonidine significantly improved impaired retinal vascular autoregulation in normal tension glaucoma patients, but short-term alteration in visual function could not be demonstrated.

Effects of dorzolamide-timolol and brimonidine-timolol on retinal vascular autoregulation and ocular perfusion pressure in primary open angle glaucoma.

PURPOSE: To assess whether dorzolamide 2%-timolol 0.5% (D/T) and/or brimonidine 0.2%-timolol 0.5% (B/T) alters retinal vascular autoregulation (RVA) and seated ocular perfusion pressure (sOPP) in primary open angle glaucoma (POAG) patients who demonstrate retinal vascular dysregulation (RVD) on timolol 0.5% alone. METHODS: In this prospective, observer-masked, crossover study, 21 POAG patients with untreated intraocular pressure (IOP) >21 mmHg were treated for 6 weeks with timolol 0.5%. Subsequently, we measured inferior temporal retinal artery blood flow in the left eye with subjects seated and then while reclined for 30 min using the Canon Laser Blood Flowmeter. Subjects with a change in retinal blood flow in response to posture change outside of the range previously found in healthy subjects were designated as having RVD and randomized to either D/T or B/T for 6 weeks and re-tested. This was followed by treatment with the opposite medication. RESULTS: Seven of the 21 subjects demonstrated RVD in response to posture change following timolol 0.5%. Multiple linear regression analysis indicated that lower sOPP was the main determinant of RVD (P=0.033). After treatment with D/T, all 7 converted from RVD to normal RVA status (P=0.001). Four of 6 subjects showed a similar return to normal RVA following B/T (P=0.066). Mid-morning sOPP was 41.1±5.5 mmHg post-timolol, 46.3±6.5 mmHg post-D/T, and 38.6±6.0 mmHg post-B/T (D/T vs. B/T, P=0.026). CONCLUSIONS: D/T significantly improved RVA in POAG patients exhibiting RVD while on timolol 0.5% alone. D/T also increased sOPP compared to B/T. There was no significant difference (P=0.37) between D/T and B/T in improving RVA.

Effect of brimonidine on retinal blood flow autoregulation in primary open-angle glaucoma.

PURPOSE: To determine whether topically applied brimonidine affects the retinal hemodynamic autoregulatory response to posture change in patients with normal tension glaucoma. METHODS: Six patients with normal tension glaucoma (primary open-angle glaucoma and maximum untreated intraocular pressure <22 mmHg) in each eye were studied. We retrospectively reviewed retinal hemodynamic data acquired when the patients were off and on treatment with brimonidine 0.15% (twice a day, both eyes) during the course of their care. At each testing session, vessel diameter and blood speed at the same site along the inferior temporal retinal artery of 1 eye were measured while sitting, while reclining for 30 min, and again while sitting using a retinal laser Doppler instrument. Blood flow was computed automatically. Brachial artery blood pressure and heart rate were also measured. The Wilcoxon signed rank test was used to assess the statistical significance of the differences in each measured parameter while subjects were on and off brimonidine. RESULTS: Off brimonidine, the mean blood flow rate increased by 68.0%±34.3% (range: +17% to +108%) after 30 min in reclined posture compared to baseline-seated measures. On brimonidine, the mean blood flow rate increased by 8.9%±16.8% (range: -9.7 to +28.0%) after 30 min in reclined posture compared to baseline-seated measures. The difference in the posture-induced changes for blood flow rate while on brimonidine compared to off brimonidine was statistically significant (P=0.027). CONCLUSIONS: Off brimonidine, the patients exhibited marked increases in retinal blood flow while reclining. On brimonidine, the hemodynamic changes were consistent with normal autoregulatory control of retinal blood flow.

Defective myogenic response to posture change in retinal vessels of well-controlled type 1 diabetic patients with no retinopathy.

PURPOSE: The current approach to the prevention of diabetic retinopathy relies on intensive anti-diabetes treatment and is only partially successful. A marker of retinopathy risk would enable strategies of surveillance, screening of adjunct drugs, and targeted drug interventions. The authors sought to identify early abnormalities of retinal vessels that are not prevented by the current therapeutic approach. METHODS: Retinal thickness (an informer of vascular permeability) and hemodynamic parameters at baseline and longitudinally were measured in 27 subjects (age, 32 ± 9 years [mean ± SD]) with well-controlled type 1 diabetes of 12.4 ± 6.4 years' duration and no retinopathy, and in 27 control subjects. In a subset of 17 patients and 11 controls, the hemodynamic response to reclining, a postural change that increases retinal perfusion pressure, was measured. RESULTS: Baseline foveal thickness and hemodynamic parameters were similar in the diabetic and control subjects. Foveal thickness increased over 12 months in the diabetic subjects, from 217 ± 22 µm to 222 ± 20 µm (P = 0.0036), remaining however within the normal range. Reclining uncovered in 47% of diabetic subjects (P = 0.016 compared with controls) an absent myogenic response (i.e., unchanged or increased arterial diameter instead of the normal decrease). The patterns were repeatable. Only the diabetic group with defective vasoconstriction showed widening arterial diameter over 12 months, a change presaging vascular dilatation in diabetic retinopathy. CONCLUSIONS: Defective myogenic response to pressure was the first detectable abnormality of retinal vessels in subjects with well-controlled type 1 diabetes. Because of its selective occurrence, interpretability in individual patients, and pathogenic potential, the abnormality deserves evaluation as a risk marker for retinopathy.