Baseline structural characteristics of the optic nerve head and retinal nerve fiber layer are associated with progressive visual field loss in patients with open-angle glaucoma.

AIMS: To examine the relationship between baseline structural characteristics of the optic nerve head (ONH) and retinal nerve fiber layer (RNFL) and functional disease progression in patients with open-angle glaucoma (OAG) over 5 years. METHODS: 112 OAG patients were prospectively examined at baseline and every 6 months over a period of five years. Structural glaucomatous changes were examined with optical coherence tomography (OCT) and Heidelberg retinal tomography-III (HRT-III), and functional disease progression with automated perimetry (Humphrey visual fields). Cox proportional hazard models were used to assess the relationship between baseline structural measurements and functional disease progression. RESULTS: From baseline over a 5-year period, statistically significant increases were found in OCT disc (D) area (p<0.001), cup (C) area (p<0.001), C/D area ratio (p<0.001), C/D horizontal ratio (p<0.001), C/D vertical ratio (p = 0.018), and a decrease in superior RNFL thickness (p = 0.008). Statistically significant increases were found in HRT-III C volume (p = 0.021), C/D area ratio (p = 0.046), mean C depth (p = 0.036), C shape (p = 0.008), and height variation contour (p = 0.020). Functional disease progression was detected in 37 of the 112 patients (26 of European descent and 11 of African descent; 33%). A statistically significant shorter time to functional progression was seen in patients with larger baseline OCT D area (p = 0.008), C area (p = 0.003), thicker temporal RNFL (p = 0.003), and in patients with a larger HRT-III C area (p = 0.004), C/D area ratio (p = 0.004), linear C/D ratio (p = 0.007), C shape (p = 0.032), or smaller rim area (p = 0.039), rim volume (p = 0.005), height variation contour (p = 0.041), mean RNFL thickness (p<0.001), or RNFL cross-sectional area (p = 0.002). CONCLUSION: Baseline ONH and RNFL structural characteristics were associated with a significantly shorter time to functional glaucomatous progression and visual field loss through the five-year period in OAG patients.

Efficacy and safety of bromfenac 0.075% formulated in DuraSite for pain and inflammation in cataract surgery.

Introduction: Bromfenac is a topical ophthalmic non-steroidal anti-inflammatory drug (NSAID) used to reduce pain and treat post-operative inflammation after cataract surgery. Bromfenac 0.075% in the DuraSite™ vehicle is a newly-approved formulation which has been shown to be efficacious and safe for use in cataract surgery to reduce pain and treat inflammation. It has been shown to have a slightly better posterior segment ocular bioavailability compared to similar topical ophthalmic NSAIDs. However, there is a paucity of studies investigating its role in the prevention and treatment of post-operative pseudophakic cystoid macular edema. Areas covered: In this review, the authors provide an overview of similar products available, describe the novelty of bromfenac 0.075% in the DuraSite vehicle, and discuss the relevant clinical studies to determine if the formulation is safe and efficacious. Expert opinion: Bromfenac 0.075% in the DuraSite vehicle is a new topical ophthalmic medication which has been approved by the FDA for the prevention of pain and treatment of post-operative inflammation. It provides cataract surgeons with an additional medication for cataract surgery. However, no robust studies have been performed showing the effect that it has on the reduction or prevention of post-operative pseudophakic cystoid macular edema.

Targeting Transforming Growth Factor-ß Signaling in Primary Open-Angle Glaucoma.

Transforming growth factor-ß (TGF-ß) may play a role in the pathogenesis of primary open-angle glaucoma (POAG). Elevated levels of TGF-ß are found in the aqueous humor and in reactive optic nerve astrocytes in patients with glaucoma. In POAG, aqueous humor outflow resistance at the trabecular meshwork (TM) leads to increased intraocular pressure and retinal ganglion cell death. It is hypothesized that TGF-ß increases outflow resistance by altering extracellular matrix homeostasis and cell contractility in the TM through interactions with other proteins and signaling molecules. TGF-ß may also be involved in damage to the optic nerve head. Current available therapies for POAG focus exclusively on lowering intraocular pressure without addressing extracellular matrix homeostasis processes in the TM. The purpose of this review is to discuss possible therapeutic strategies targeting TGF-ß in the treatment of POAG. Herein, we describe the current understanding of the role of TGF-ß in POAG pathophysiology, and examine ways TGF-ß may be targeted at the levels of production, activation, downstream signaling, and homeostatic regulation.

Baseline retrobulbar blood flow is associated with both functional and structural glaucomatous progression after 4†years.

BACKGROUND/AIMS: Previous studies suggest that vascular abnormalities are involved in the pathogenesis of open-angle glaucoma. This study aims to examine the relationship of baseline retrobulbar blood flow measurements with functional and structural glaucomatous progression in patients with open-angle glaucoma over 4 years. METHODS: In this study, 112 patients with open-angle glaucoma were examined at baseline and 78 with retrobulbar blood flow assessments were followed to 4 years. Colour Doppler imaging was used to evaluate retrobulbar blood flow. Structural disease progression was examined with optical coherence tomography and Heidelberg Retinal Tomography III. Functional disease progression was monitored with automated perimetry using Humphrey visual fields. Mixed-model analysis of covariance was used to test for significance of changes from baseline to 4-year follow-up. Two-sample t tests and χ2 tests were used to test for baseline blood flow differences between patients who progressed and those who did not progress. RESULTS: Patients who progressed structurally had a statistically significant lower baseline mean ophthalmic artery peak systolic velocity (PSV) (p=0.024) and ophthalmic artery end diastolic velocity (EDV) (p=0.012) compared with those who did not progress. Similarly, a lower baseline mean ophthalmic artery PSV (p=0.031) and ophthalmic artery EDV (p=0.005) were associated with patients who progressed functionally compared with those who did not progress after 4 years. CONCLUSIONS: In this study population, lower baseline ophthalmic artery blood flow velocities were associated with simultaneous structural and functional glaucoma progression after 4 years.

Reductions in Retrobulbar and Retinal Capillary Blood Flow Strongly Correlate With Changes in Optic Nerve Head and Retinal Morphology Over 4 Years in Open-angle Glaucoma Patients of African Descent Compared With Patients of European Descent.

PURPOSE: To investigate the relationship of changes in ocular blood flow with optic nerve head (ONH) and retinal morphology in open-angle glaucoma (OAG) patients of African versus European descent (ED) over 4 years. MATERIALS AND METHODS: In this study, 112 patients with OAG were examined at baseline, 79 [59 ED, 20 African descent (AD)] of which were followed for 4 years. Retinal capillary blood flow was assessed with Heidelberg retinal flowmetry. Retrobulbar blood flow was measured by color Doppler imaging. Retinal structural changes were examined with optical coherence tomography and Heidelberg retinal tomography-III. Mixed-model analysis of covariance was used to test for the significance of change from baseline to 4-year follow-up, and Pearson correlation coefficients were calculated to evaluate linear associations. RESULTS: In OAG patients of AD, structural changes of the ONH demonstrated a strong association with the end diastolic velocities and resistive indices of the short posterior ciliary arteries over 4 years. In addition, there was a significantly larger increase in the avascular area of the inferior retina in patients of AD, and this reduction in retinal capillaries strongly correlated with a reduction in macular thickness. CONCLUSIONS: Reductions in retinal capillary and retrobulbar blood flow strongly correlated with changes in the ONH and macular thickness over 4 years in OAG patients of AD compared with ED. These data suggest that ocular vascular health may be a more influential contributing factor in the pathophysiology of OAG in patients of AD compared with ED.

Novel therapies for open-angle glaucoma.

Open-angle glaucoma is a multifactorial optic neuropathy characterized by progressive loss of retinal ganglion cells and their axons. It is an irreversible disease with no established cure. The only currently approved treatment is aimed at lowering intraocular pressure, the most significant risk factor known to date. However, it is now clear that there are other risk factors involved in glaucoma's pathophysiology. To achieve future improvements in glaucoma management, new approaches to therapies and novel targets must be developed. Such therapies may include new tissue targets for lowering intraocular pressure, molecules influencing ocular hemodynamics, and treatments providing neuroprotection of retinal ganglion cells. Furthermore, novel drug delivery systems are in development that may improve patient compliance, increase bioavailability, and decrease adverse side effects.