Literature review and meta-analysis of translaminar pressure difference in open-angle glaucoma.

There is increasing evidence in the literature regarding translaminar pressure difference's (TPD) role in the pathophysiology of glaucoma. The optic nerve is exposed not only to intraocular pressure in the eye, but also to intracranial pressure (ICP), as it is surrounded by cerebrospinal fluid in the subarachnoid space. Although pilot studies have identified the potential importance of TPD in glaucoma, limited available data currently prevent a comprehensive description of the role that TPD may have in glaucomatous pathophysiology. In this review, we present all available qualified data from a systematic review of the literature of the role of TPD in open-angle glaucoma (OAG). PubMed (Medline), OVID Medline, ScienceDirect, SpringerLink, and all available library databases were reviewed and subsequent meta-analysis of pooled mean differences are presented where appropriate. Five papers including 396 patients met criteria for inclusion to the analysis. Importantly, we included all observational studies despite differences in ICP measurement methods, as there is no consensus regarding best-practice ICP measurements in glaucoma. Our results show that not only TPD is higher in glaucoma patients compared with healthy subjects, it is related to structural glaucomatous changes of the optic disc. Our analysis suggests further longitudinal prospective studies are needed to investigate the influence of TPD in OAG, with a goal of overcoming methodological weaknesses of previous studies.

Republished review: The world through a lens: the vision of Sir Harold Ridley.

Sir Harold Ridley is recognised today as the inventor of intraocular lens implantation, one the most successful and common procedures in all of surgery. His story, however, is not largely one of triumph and public accolade. This paper reviews Ridley's invention of the intraocular lens and highlights the struggles he faced after his discovery.

The world through a lens: the vision of Sir Harold Ridley.

Sir Harold Ridley is recognised today as the inventor of intraocular lens implantation, one the most successful and common procedures in all of surgery. His story, however, is not largely one of triumph and public accolade. This paper reviews Ridley's invention of the intraocular lens and highlights the struggles he faced after his discovery.

Color Doppler imaging of retrobulbar hemodynamics in Sturge-Weber syndrome-associated glaucoma.

PURPOSE: Sturge-Weber syndrome (SWS) is frequently associated with early onset glaucoma in the eye on the same side as the facial angioma. The exact cause of glaucoma in SWS is poorly understood and difficult to treat. The purpose of this study is to investigate the ocular hemodynamics of children with SWS-associated glaucoma using color Doppler imaging techniques. METHODS: This is a prospective study of 10 pediatric patients with unilateral SWS-associated glaucoma. Color Doppler imaging was used to measure the peak systolic velocity and the end diastolic velocity of both the ophthalmic and central retinal arteries in the glaucomatous eye compared to the fellow healthy eye. RESULTS: Twenty eyes of 10 children with SWS (6 boys) with unilateral glaucoma were included in the prospective study. The mean age of the 10 participants was 5.5 years. When compared to their contralateral normal eyes, the glaucomatous eyes had greater CDR (p<0.001) and a myopic shift (p=0.04). No significant differences were found in the measurements of ocular blood flow velocities of the ophthalmic and central retinal arteries. CONCLUSIONS: Vascular pathology has been proposed to play a role in SWS glaucoma etiology. The authors did not find arterial retrobulbar blood flow differences between the glaucomatous and the fellow normal eye. Since the primary vascular anomaly in patients with SWS is in the venous plexus, a bigger prospective trial is warranted in order to better understand and treat children with SWS glaucoma.

Comparison of visual function and ocular hemodynamics between pre- and post-menopausal women.

PURPOSE: The incidence of eye disease increases with age and can often be linked to worsening cardiovascular function and increasing intraocular pressure. Estrogen is known to have vasodilatory effects in the systemic circulation. Decreased estrogen levels during menopause may therefore complicate or contribute to ocular pathologies as estrogen receptors are found in both retinal and choroidal tissue. The purpose of this investigation was to determine the effects of menopause on visual function and cardiovascular and ocular hemodynamics. METHODS: Twelve premenopausal and 24 postmenopausal women were evaluated at the Indiana University School of Medicine during a single study visit. Vision screening and ocular blood flow evaluations were performed, including blood pressure, heart rate, visual acuity, contrast sensitivity, intraocular pressure, and retinal capillary and retrobulbar blood flow imaging. Vision and ocular hemodynamics were compared using unpaired Student t-tests with p<0.05 regarded as statistically significant. RESULTS: The premenopausal group had significantly lower heart rate (-16.1 b/m, p=0.0001) and systolic blood pressure (-17.7 mmHg, p=0.003) than postmenopausal subjects. Contrast sensitivity was significantly higher (measured in log units) in premenopausal women in both the right (0.25, p=0.039; 0.16, p=0.039) and left (0.45, p=0.001; 0.27, p=0.032) eyes at 9 and 18 cycles per degree, respectively. Premenopausal women also had significantly lower intraocular pressure in both the right (-2.19 mmHg, p=0.024) and left (-1.74 mmHg, p=0.035) eyes. Total ocular perfusion was not significantly different between groups. CONCLUSIONS: This pilot work suggests that postmenopausal women have lower contrast sensitivity detection and elevated intraocular pressures compared to premenopausal women. Premenopausal women have lower cardiovascular risk factors, while total ocular circulation was similar to postmenopausal women.

A comparative study of the effects of brinzolamide and dorzolamide on retinal oxygen saturation and ocular microcirculation in patients with primary open-angle glaucoma.

AIMS: To assess the effects of brinzolamide and dorzolamide on ocular haemodynamics and retinal oxygen saturation in patients with primary open-angle glaucoma (OAG). METHODS: Fifteen patients with OAG were evaluated in a randomised, cross-over, double-blind study. They were treated with either brinzolamide or dorzolamide for 3 months and then crossed-over after a 4-week washout period. They were given timolol during a 4-week run-in period and during washout. The following were performed after run-in, after washout and after each treatment period: adverse events check, measurement of visual acuity, contrast sensitivity, blood pressure, heart rate, and intraocular pressure, and fundus examination. Ocular blood flow was assessed using confocal scanning laser Doppler flowmetry (HRF) and colour Doppler imaging (CDI). Retinal oxygenation levels were determined using a non-invasive measurement of haemoglobin oxygen saturation by digital photographic fundus oximetry. RESULTS: Both brinzolamide and dorzolamide reduced the number of zero-flow pixels in the retina as measured by HRF, suggesting an increase in retinal blood flow (-6.86 and -0.452 respectively) with brinzolamide treatment resulting in fewer zero-flow pixels than dorzolamide (-6.41) (p = 0.024). Both brinzolamide and dorzolamide increased oxygen saturation in the retina as measured by photographic retinal oximetry in the superior (0.82 (p = 0.002) and 0.87 (p = 0.005)) and inferior (0.88 (p = 0.035) and 0.82 (p = 0.002)) retinal veins. No significant changes were found in CDI measurements of the retrobulbar blood supply during either treatment. CONCLUSION: This pilot study suggests that brinzolamide and dorzolamide may increase retinal oxygen saturation in patients with OAG.

The response of retrobulbar vasculature to hypercapnia in primary open-angle glaucoma and ocular hypertension.

PURPOSE: To evaluate the physiological effects of hypercapnia on the retrobulbar vasculature in ocular hypertension (OH) and open-angle glaucoma (OAG). METHODS: Peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistive index (RI) of the ophthalmic (OA) and central retinal arteries (CRA) were evaluated in 12 eyes with OH and 8 eyes with OAG using color Doppler imaging. Measurements were taken before and during hypercapnia. RESULTS: Patients with OAG were found to have increased EDV (p < 0.035) of the CRA, and decreased PSV (p < 0.097) and EDV (p < 0.098) of the OA, during hypercapnia. Patients with OH had increased PSV (p < 0.062) and EDV (p < 0.072) of the CRA during hypercapnia. Patients with OH also demonstrated a greater percent change in the calculated RI (p < 0.065) of the CRA in response to hypercapnia when compared to OAG. The mean RI of the CRA decreased during hypercapnia. DISCUSSION: Patients with OH were found to have a normal vasodilatory response within the retrobulbar vasculature during hypercapnia resulting in increased volumetric blood flow to the retina while patients with OAG did not, suggesting there is vasospasm at or downstream from the CRA resulting in decreased volumetric blood flow to the retina.

A comparison of the effects of dorzolamide/timolol fixed combination versus latanoprost on intraocular pressure and pulsatile ocular blood flow in primary open-angle glaucoma patients.

PURPOSE: To evaluate the effects of dorzolamide/timolol fixed combination (D/T) compared to latanoprost on intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) in primary open-angle glaucoma (POAG) patients. METHODS: Thirty patients with POAG were randomized in an open-label, cross-over study. Intraocular pressure reduction was achieved by 4 weeks medical therapy with D/T twice daily or latanoprost 0.005% dosed once in the evening. During a 4-week run-in and a 4-week wash-out period between study arms, patients ceased use of all other glaucoma medications and used timolol maleate 0.5% twice daily. Primary efficacy variables were IOP and POBF. RESULTS: There was no difference in baseline IOP and POBF parameters between the two study arms. Both D/T and latanoprost statistically significantly reduced IOP by 4.6 mmHg (p < 0.0001) and 3.75 mmHg (p < 0.0001) and increased POBF by 2.048 microl/second (p = 0.0030) and 2.147 microl/second (p = 0.0009), respectively. Repeated measures anova detected significant changes in POBF with treatment (p = 0.0361). Dorzolamide/timolol fixed combination statistically significantly increased pulse volume by 0.767 microl (p = 0.0087), while latanoprost therapy had no significant effect (p = 0.2407). CONCLUSIONS: Both drugs had similar effects in terms of IOP reduction. Dorzolamide/timolol significantly increased pulse volume while latanoprost had no effect. Further studies are necessary to establish whether the enhancement of choroidal blood flow can prevent glaucoma progression.

Effect of intravenous droperidol on intraocular pressure and retrobulbar hemodynamics.

PURPOSE: Topically-applied dopamine antagonists reduce intraocular pressure (IOP) and inrease retinal blood flow in animal models. We examined the acute effects of intravenous infusion of a dopamine blocker (droperidol) on these parameters in healthy humans. METHODS: Sixteen subjects free from ocular or systemic disease (mean age 33 +/- 10 yrs) received either 5 mg i.v. droperidol over 5 minutes, or i.v. saline placebo in double-masked fashion. IOP was determined 30 and 60 minutes later, while color Doppler imaging was used to determine flow velocities in the ophthalmic, central retinal, and nasal and temporal posterior ciliary arteries 60 minutes after drug infusion. RESULTS: 30 minutes after drug infusion, IOP was reduced 6.0 mmHg as compared with baseline (p<0.001); after 60 minutes, IOP remained reduced by 3.7 mmHg (p<0.001). Placebo had no effect on IOP. While droperidol slightly elevated blood pressure and increased the calculated ocular perfusion pressure, the drug reduced visual acuity and contrast sensitivity (p<0.05). Droperidol elevated peak systolic velocity in the central retinal and nasal posterior ciliary arteries, without changing end-diastolic velocity or the resistance index in either of these vessels. Droperidol had no effect on flow velocities in the ophthalmic artery or the temporal posterior ciliary artery. CONCLUSIONS: The rapid and marked ocular hypotension resulting from intravenous droperidol suggests that this agent may prove useful in the management of acute ocular hypertension. The retrobulbar changes consequent to the ocular tension reduction likely represent autoregulatory responses to altered ocular perfusion pressure.