Vital Paulino Costa

The impact of ocular blood flow in glaucoma.

Two principal theories for the pathogenesis of glaucomatous optic neuropathy (GON) have been described--a mechanical and a vascular theory. Both have been defended by various research groups over the past 150 years. According to the mechanical theory, increased intraocular pressure (IOP) causes stretching of the laminar beams and damage to retinal ganglion cell axons. The vascular theory of glaucoma considers GON as a consequence of insufficient blood supply due to either increased IOP or other risk factors reducing ocular blood flow (OBF). A number of conditions such as congenital glaucoma, angle-closure glaucoma or secondary glaucomas clearly show that increased IOP is sufficient to lead to GON. However, a number of observations such as the existence of normal-tension glaucoma cannot be satisfactorily explained by a pressure theory alone. Indeed, the vast majority of published studies dealing with blood flow report a reduced ocular perfusion in glaucoma patients compared with normal subjects. The fact that the reduction of OBF often precedes the damage and blood flow can also be reduced in other parts of the body of glaucoma patients, indicate that the hemodynamic alterations may at least partially be primary. The major cause of this reduction is not atherosclerosis, but rather a vascular dysregulation, leading to both low perfusion pressure and insufficient autoregulation. This in turn may lead to unstable ocular perfusion and thereby to ischemia and reperfusion damage. This review discusses the potential role of OBF in glaucoma and how a disturbance of OBF could increase the optic nerves sensitivity to IOP.

Treatment Outcomes in the Ahmed Baerveldt Comparison Study after 1 Year of Follow-up

PURPOSE To determine the relative efficacy and complications of the Ahmed glaucoma valve (AGV) model FP7 (New World Medical, Ranchos Cucamonga, CA) and the Baerveldt glaucoma implant (BGI) model 101-350 (Abbott Medical Optics, Abbott Park, IL) in refractory glaucoma. DESIGN Multicenter, randomized, controlled clinical trial. PARTICIPANTS Two hundred seventy-six patients, including 143 in the AGV group and 133 in the BGI group. METHODS Patients 18 to 85 years of age with refractory glaucoma having intraocular pressure (IOP) of 18 mmHg or more in whom an aqueous shunt was planned were randomized to undergo implantation of either an AGV or a BGI. MAIN OUTCOME MEASURES The primary outcome was failure, defined as IOP >21 mmHg or not reduced by 20% from baseline, IOP ≤5 mmHg, reoperation for glaucoma or removal of implant, or loss of light perception vision. Secondary outcomes included mean IOP, visual acuity, use of supplemental medical therapy, and complications. RESULTS Preoperative IOP (mean±standard deviation [SD]) was 31.2±11.2 mmHg in the AGV group and 31.8±12.5 mmHg in the BGI group (P = 0.71). At 1 year, mean±SD IOP was 15.4±5.5 mmHg in the AGV group and 13.2±6.8 mmHg in the BGI group (P = 0.007). The mean±SD number of glaucoma medications was 1.8±1.3 in the AGV group and 1.5±1.4 in the BGI group (P = 0.071). The cumulative probability of failure was 16.4% (standard error [SE], 3.1%) in the AGV group and 14.0% (SE, 3.1%) in the BGI group at 1 year (P = 0.52). More patients experienced early postoperative complications in the BGI group (n = 77; 58%) compared with the AGV group (n = 61; 43%; P = 0.016). Serious postoperative complications associated with reoperation, vision loss of ≥2 Snellen lines, or both occurred in 29 patients (20%) in the AGV group and in 45 patients (34%) in the BGI group (P = 0.014). CONCLUSIONS Although the average IOP after 1 year was slightly higher in patients who received an AGV, there were fewer early and serious postoperative complications associated with the use of the AGV than the BGI.

The effects of antiglaucoma and systemic medications on ocular blood flow

Based on the body of evidence implicating ocular blood flow disturbances in the pathogenesis of glaucoma, there is great interest in the investigation of the effects of antiglaucoma drugs and systemic medications on the various ocular vascular beds. The primary aim of this article was to review the current data available on the effects of antiglaucoma drugs and systemic medications on ocular blood flow. We performed a literature search in November 2002, which consisted of a textword search in MEDLINE for the years 1968-2002. The results of this review suggest that there is a severe lack of well-designed long-term studies investigating the effects of antiglaucoma and systemic medications on ocular blood flow in glaucomatous patients. However, among the 136 articles dealing with the effect of antiglaucoma drugs on ocular blood flow, only 36 (26.5%) investigated the effects of medications on glaucoma patients. Among these 36 articles, only 3 (8.3%) were long-term studies, and only 16 (44.4%) were double-masked, randomized, prospective trials. Among the 33 articles describing the effects of systemic medications on ocular blood flow, only 11 (33.3%) investigated glaucoma patients, of which only one (9.1%) was a double-masked, randomized, prospective trial. Based on this preliminary data, we would intimate that few antiglaucoma medications have the potential to directly improve ocular blood flow. Unoprostone appears to have a reproducible antiendothelin-1 effect, betaxolol may exert a calcium-channel blocker action, apraclonidine consistently leads to anterior segment vasoconstriction, and carbonic anhydrase inhibitors seem to accelerate the retinal circulation. Longitudinal, prospective, randomized trials are needed to investigate the effects of vasoactive substances with no hypotensive effect on the progression of glaucoma.

Ocular perfusion pressure in glaucoma

This review article discusses the relationship between ocular perfusion pressure and glaucoma, including its definition, factors that influence its calculation and epidemiological studies investigating the influence of ocular perfusion pressure on the prevalence, incidence and progression of glaucoma. We also list the possible mechanisms behind this association, and discuss whether it is secondary to changes in intraocular pressure, blood pressure or both. Finally, we describe the circadian variation of ocular perfusion pressure and the effects of systemic and topical medications on it. We believe that the balance between IOP and BP, influenced by the autoregulatory capacity of the eye, is part of what determines whether an individual will develop optic nerve damage. However, prospective, longitudinal studies are needed to better define the role of ocular perfusion pressure in the development and progression of glaucoma.

Use of colour Doppler imaging in ocular blood flow research.

The main objective of this report is to encourage consistent quality of testing and reporting within and between centres that use colour Doppler imaging (CDI) for assessment of retrobulbar blood flow. The intention of this review is to standardize methods in CDI assessment that are used widely, but not to exclude other approaches or additional tests that individual laboratories may choose or continue to use.

Three-year Treatment Outcomes in the Ahmed Baerveldt Comparison Study

PURPOSE To compare 3-year outcomes and complications of the Ahmed FP7 Glaucoma Valve (AGV) (New World Medical, Cucamonga, CA) and the Baerveldt Glaucoma Implant (BGI) 101-350 (Abbott Medical Optics, Abbott Park, IL) for the treatment of refractory glaucoma. DESIGN Multicenter, randomized, controlled clinical trial. PARTICIPANTS A total of 276 patients: 143 in the AGV group and 133 in the BGI group. METHODS Patients aged 18 to 85 years with refractory glaucoma and intraocular pressures (IOPs) ≥ 18 mmHg in whom an aqueous shunt was planned were randomized to an AGV or a BGI. MAIN OUTCOME MEASURES The IOP, visual acuity (VA), supplemental medical therapy, complications, and failure (IOP >21 mmHg or not reduced by 20% from baseline, IOP <5 mmHg, reoperation for glaucoma or removal of implant, or loss of light perception vision). RESULTS At 3 years, IOP (mean ± standard deviation) was 14.3 ± ± 4.7 mmHg (AGV group) and 13.1 ± 4.5 mmHg (BGI group) (P = 0.086) on 2.0 ± 1.4 and 1.5 ± 1.4 glaucoma medications, respectively (P = 0.020). The cumulative probabilities of failure were 31.3% (standard error [SE], 4.0%) (AGV) and 32.3% (4.2%) (BGI) (P = 0.99). Postoperative complications associated with reoperation or vision loss of >2 Snellen lines occurred in 24 patients (22%) (AGV) and 38 patients (36%) (BGI) (P = 0.035). The mean change in the logarithm of the minimum angle of resolution VA at 3 years was similar (AGV: 0.21 ± 0.88, BGI: 0.26 ± 0.74) in the 2 treatment groups at 3 years (P = 0.66). The cumulative proportion of patients (SE) undergoing reoperation for glaucoma before the 3-year postoperative time point was 14.5% (3.0%) in the AGV group compared with 7.6% (2.4%) in the BGI group (P = 0.053, log rank). The relative risk of reoperation for glaucoma in the AGV group was 2.1 times that of the BGI group (95% confidence interval, 1.0-4.8; P = 0.045, Cox proportional hazards regression). CONCLUSIONS Implantation of the AGV was associated with the need for significantly greater adjunctive medication to achieve equal success relative to implantation of the BGI and resulted in a greater relative risk of reoperation for glaucoma. More subjects experienced serious postoperative complications in the BGI group than in the AGV group.

Clinical Findings and Hemodynamic Changes Associated with Severe Occlusive Carotid Artery Disease

OBJECTIVE The purpose of the study was to evaluate the ophthalmologic findings and to analyze the retrobulbar hemodynamics of patients with severe (greater than 70% stenosis) occlusive carotid artery disease (OCAD) by means of color Doppler imaging (CDI). DESIGN A case-controlled study. PARTICIPANTS Fifty-six consecutive patients with severe OCAD and an age- and sex-matched control group consisting of 56 healthy patients without OCAD were studied. INTERVENTION All 112 patients underwent a complete ophthalmologic examination. Color Doppler imaging of both orbits was performed by one masked investigator. MAIN OUTCOME MEASURES Peak systolic velocity, end diastolic velocity, and the resistive index of the ophthalmic, central retinal, and temporal short posterior ciliary arteries were measured. The authors compared the hemodynamic parameters measured in patients with severe OCAD with those obtained in the control group. The hemodynamic parameters of patients with asymmetric OCAD (stenosis > 70% in one internal carotid artery and stenosis < 50% in the contralateral artery) were also compared. In an attempt to determine risk factors associated with the ocular ischemic syndrome (OIS), the authors compared patients with severe OCAD and OIS with patients with severe OCAD without OIS. RESULTS Peak systolic and end diastolic velocities in the ophthalmic, central retinal, and temporal short posterior ciliary arteries were significantly lower in patients with severe OCAD (P < 0.01). The mean resistive indices in the central retinal and temporal short posterior ciliary arteries were higher in the group with severe OCAD (P < 0.01). Similar results were obtained in the analysis of 25 patients with asymmetric carotid stenosis. Younger age (P = 0.012), severe bilateral OCAD (P = 0.01), high-grade carotid stenosis (P = 0.013), and reversed ophthalmic artery flow (P = 0.038) were significant risk factors for OIS. CONCLUSIONS Patients with severe OCAD show hemodynamic changes that suggest reduced retrobulbar blood flow. Patients with severe bilateral OCAD, high-grade carotid stenosis, and reversed ophthalmic artery flow may have a greater risk of developing OIS.

Blood pressure and glaucoma

Although intraocular pressure (IOP) is considered the main risk factor for the development of glaucoma and the only parameter subject to treatment, there is sufficient evidence to suggest that glaucoma may continue to progress despite lowering patients’ IOP to targeted levels. Several studies have implicated vascular risk factors in the pathogenesis of glaucoma. Among them, blood pressure (BP) and ocular perfusion pressure have become increasingly important. Although clinicians cannot currently visualise ocular blood flow directly, they can easily measure glaucoma patients’ BP and IOP to calculate their ocular perfusion pressure and quantify the vascular changes. The purpose of this review article is to discuss the relationship between BP and IOP, BP and glaucoma, and perfusion pressure and glaucoma. We discuss the importance of autoregulation to maintain the adequate perfusion of the optic nerve head, and suggest that ocular perfusion pressure and its fluctuation may be parameters that need to be measured in glaucoma patients.

Discrimination between normal and glaucomatous eyes with visual field and scanning laser polarimetry measurements

AIM To evaluate the ability of structural parameters (as determined by retinal nerve fibre layer (RNFL) measurements obtained with the scanning laser polarimeter (SLP-NFA/GDx)) and functional parameters (as determined by automated perimetry) to discriminate between normal and glaucomatous eyes. METHODS In a case-control study, a total of 91 normal subjects and 94 patients with glaucoma underwent automated perimetry and RNFL measurements obtained with the SLP. Three independent scans of each eye were obtained and a mean image was created and used for further analysis. Only one eye per individual was randomly included in the study. The sensitivity (Se) and specificity (Sp) of 12 RNFL parameters were calculated according to the SLP internal normative database. The Se and Sp of the visual field (VF) global indices and the glaucoma hemifield test (GHT) were also calculated according to the instruments normative database. Receiver operator characteristic (ROC) curves were built for each SLP parameter and VF index. Fishers linear discriminant formulas (LDFs) were developed for VF indices (VF LDF), SLP measurements (SLP LDF), and both examinations (combined LDF). RESULTS According to the SLP internal database, the parameters with better Se and Sp were: superior/nasal ratio (Se = 58.5%; Sp = 86.8%), and GDx the number (Se = 43.3%; Sp = 96.7%). The construction of an ROC curve for the number resulted in Se = 84% and Sp = 79%. The creation of LDFs improved both the sensitivities and specificities when compared with isolated parameters SLP LDF (Se = 90.4%; Sp = 82.4%), VF LDF (Se = 89.4%; Sp = 89.0%), and combined LDF (Se = 93.0%; Sp = 90.1%). The sensitivity to diagnose early and moderate glaucomatous damage observed with the GHT was lower than that obtained with the number (p<0.01). CONCLUSIONS Creation of LDFs enhanced the Se and Sp for both VF and SLP. Integration of SLP and VF in a combined LDF reached the highest Se/Sp relation, suggesting that these examinations may be additive concerning the diagnosis of glaucoma. The SLP parameter the number may be more sensitive than the GHT in diagnosing early and moderate glaucomatous damage.

Needling versus Medical Treatment in Encapsulated Blebs: A Randomized, Prospective Study

OBJECTIVE The purpose of the study is to compare the efficacy and safety of transconjunctival needling and medical treatment in eyes with encapsulated blebs. DESIGN A randomized, prospective study. PARTICIPANTS Two hundred eighty-two eyes that underwent a guarded filtration procedure between January 1994 and January 1996 at the Glaucoma Service of University of Campinas. INTERVENTION Encapsulated blebs developed in 25 (8.9%) of 282 eyes and were randomized to either needling (n = 14) or medical treatment with aqueous humor suppressants (n = 11). If one treatment failed to maintain intraocular pressures (IOPs) below 20 mmHg, the other treatment was initiated. If both methods failed, surgical revision or further glaucoma surgery was performed. Complete success was defined as IOP less than 20 mmHg after one treatment method. Qualified success was defined when IOPs less than 20 mmHg were obtained with both treatment methods, whereas failure was defined when IOP greater than 20 mmHg or when further surgery was indicated. MAIN OUTCOME MEASURES Intraocular pressure, vision, and number of antiglaucoma medications. RESULTS After a mean follow-up of 9.6 months, medical treatment alone was successful in ten patients (90.9%), whereas needling alone was successful in one patient (7.1%) (P = 0.00003). In the needling group, 92.9% of the eyes required aqueous humor suppressants, and 57.1% were considered qualified successes at the last follow-up (mean = 10.1 months). At the last follow-up examination, there was no statistically significant difference between the mean number of medications in both groups (P = 0.797). Further glaucoma surgery was performed in five patients (35.7%) undergoing needling and one patient (9.1%) receiving medical treatment (P = 0.162). CONCLUSIONS Medical treatment with digital pressure should be used as the initial treatment in eyes with encapsulated blebs. Needling procedures or surgical revision, methods that are more invasive and potentially associated with severe complications, should be limited to the small percentage of eyes that do not respond to medical treatment.