Medical management of primary open-angle glaucoma: Best practices associated with enhanced patient compliance and persistency

Primary open angle glaucoma is a chronic optic neuropathy often requiring lifelong treatment. Patient compliance, adherence and persistence with therapy play a vital role in improved outcomes by reducing morbidity and the economic consequences that are associated with disease progression. A literature review including searches of The Cochrane Library, MEDLINE, PubMed, conference proceedings, and bibliographies of identified articles reveals the enormous public health burden in various populations due to the impact of glaucoma associated visual impairment on the overall quality of life eg, fear of blindness, inability to work in certain occupations, driving restrictions, motor vehicle accidents, falls, and general health status. Providing specific definitions for the frequently misunderstood terms “compliance, persistence and adherence” with reference to medication use is central not only for monitoring patients’ drug dosing histories and clinical outcomes but also for subsequent research. In this review article, a summary of the advantages/disadvantages including cost-effectiveness of various medical approaches to glaucoma treatment, techniques employed for measuring patient compliance and actual patient preferences for therapy are outlined. We conclude by identifying the key barriers to ongoing treatment and suggest some best practices to enhance compliance and persistence

Comparison of United States and Canadian Glaucoma Medication Costs and Price Change from 2006 to 2013

Objective. Compare glaucoma medication costs between the United States (USA) and Canada. Methods. We modelled glaucoma brand name and generic medication annual costs in the USA and Canada based on October 2013 Costco prices and previously reported bottle overfill rates, drops per mL, and wastage adjustment. We also calculated real wholesale price changes from 2006 to 2013 based on the Average Wholesale Price (USA) and the Ontario Drug Benefit Price (Canada). Results. US brand name medication costs were on average 4x more than Canadian medication costs (range: 1.9x–6.9x), averaging a cost difference of $859 annually. US generic costs were on average the same as Canadian costs, though variation exists. US brand name wholesale prices increased from 2006 to 2013 more than Canadian prices (US range: 29%–349%; Canadian range: 9%–16%). US generic wholesale prices increased modestly (US range: −23%–58%), and Canadian wholesale prices decreased (Canadian range: −38%–0%). Conclusions. US brand name glaucoma medications are more expensive than Canadian medications, though generic costs are similar (with some variation). The real prices of brand name medications increased more in the USA than in Canada. Generic price changes were more modest, with real prices actually decreasing in Canada

Cataract prevalence following a nationwide policy to shorten wait time for cataract surgery

Background: Cataract is an age-related eye disease. Visual impairment from cataract can be restored by cataract surgery. In 2004 the Canadian federal government invested in a multibillion dollar wait time strategy to shorten the wait time for cataract surgery, a government-insured health service in all Canadian jurisdictions. We assessed if this nationwide policy reduced the number of Canadians waiting for cataract surgery as more individuals with cataract were free of cataract following the rapidly conducted surgery. Methods: In this cross-sectional study we analyzed data from randomly selected individuals aged greater than or equal to 45 years responding to the Canadian Community Health Survey (CCHS) in 2000/2001, 2003, 2005, and the CCHS Healthy Aging in 2008/2009. Information on cataract was obtained from self-reported questionnaire. The age- and sex-standardized prevalence of cataract was calculated for comparisons. Results: Cataract was reported by 0.93 million Canadians in 2000/2001, 0.99 million in 2003, 1.10 million in 2005, and 1.34 million in 2008/2009. This corresponds to an age- and sex-standardized prevalence of 8.9% in 2000/2001, 9.0% in 2003, 9.5% in 2005, and 10.2% (P <0.05) in 2008/2009. The increase in age- and sex-standardized prevalence was greater in individuals without secondary school graduation than those with secondary school graduation or higher (4.3% versus 1.3%, P < 0.05) and was seen in all Canadian provinces. The largest increase was documented in a province (Saskatchewan, from 9.8% in 2000/2001 to 12.6% in 2008/2009, P < 0.05) with the longest median wait times for cataract surgery (118 days in 2008) and the lowest number of ophthalmologists per 100,000 population (1.96 versus 3.35 national average). Conclusions: The age- and sex-standardized prevalence of cataract increased 4-5 years after the multibillion-dollar wait time strategy was launched in 2004. A lower threshold to diagnose cataract may be one potential reason for this finding. Further research is needed to understand the true reasons for the increase

Retinal blood flow in patients with primary open angle glaucoma and optic disc hemorrhage

Purpose:To investigate total retinal blood flow (TRBF) and retinal blood flow (RBF) in the superior (S) and the inferior (I) retinal hemifields in patients with primary open angle glaucoma (POAG) both with and without disc hemorrhage (DH). Methods:RBF measurements were obtained from 10 POAG with DH (mean age 71.7, SD=7.39; 9 females)and 10 age matched POAG without DH (mean age 70, SD = 5.27; 6 females) using Doppler SD-OCT (RTVue; Optovue Inc, Fremont, CA, USA) as well as bi-directional laser Doppler flowmetry with densitometry (CLBF-100, Canon, Tokyo, Japan). TRBF measurements were compared between groups, within group for SRBF and IRBF, and for inter-ocular asymmetry (ANOVA; p<0.05). Correlation between TRBF and age, and TRBF and Mean Deviation of Humphrey automated perimetry were also analyzed. Results:Venous TRBF in the POAG with DH group (n=10, 27.1 μl/min, SD 7) was significantly lower than in the age-matched POAG without DH group (n=10, 38.83 μl/min, SD 10.66, p=0.009). RBF was not significantly different between the superior and inferior hemifields for either POAG with DH (p=0.763) or POAG without DH (p=0.481). In the POAG with DH group, venous TRBF was significantly lower in the DH eye (n=8, 28.73 μl/min, SD 6.87) compared to the contralateral eye without DH (n=8, 38.44 μl/min, SD 7.11, p=0.015). There was no significant difference between IOP, MD, BP, HR and MOPP between the POAG with and without DH groups. Also, there was no significant relationship between age or MD index of automated static perimetry with venous TRBF for the POAG with, and without DH group. Conclusions:Venous TRBF was significantly lower in the POAG with DH group compared to both the POAG without DH group and the contralateral eye of the POAG with DH group. There was no within eye asymmetry when comparing SRBF and IRBF either with or without DH, or when comparing the hemifield with DH to that without

Comparison of Newly Diagnosed Ocular Hypertension and Open-Angle Glaucoma: Ocular Variables, Risk Factors, and Disease Severity

Purpose. To describe the distribution of ocular variables, risk factors, and disease severity in newly diagnosed ocular hypertension (OH) or open-angle glaucoma (OAG). Methods. Eligible subjects underwent a complete history and examination. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) obtained from multiple logistic regression models were used to compare OAG to OH and advanced to early/moderate OAG. Results. 405 subjects were enrolled: 292 (72.1%) with OAG and 113 (27.9%) with OH. 51.7% had early, 27.1% moderate, and 20.9% advanced OAG. The OR for OAG versus OH was 8.19 (P < 0.0001) for disc notch, 5.36 (P < 0.0001) for abnormal visual field, 1.45 (P = 0.001) for worsening mean deviation, 1.91 (P < 0.0001) for increased cupping, 1.03 for increased age (P = 0.030), and 0.36 (P = 0.010) for smoking. Conclusions. Increased age was a risk for OAG, and smoking decreased the risk of OAG compared to OH. Almost half of the OAG subjects had moderate/advanced disease at diagnosis

Evaluation of the retinal hemodynamics in patients with primary open angle glaucoma and differing nocturnal blood pressure profiles

Purpose: To evaluate the retinal hemodynamic response to normoxic hypercapnia among patients with primary open angle glaucoma (POAG) and differing nocturnal blood pressure (NBP) profiles, using Doppler spectral-domain optical coherence tomography (SD-OCT). Methods: Doppler SD-OCT retinal blood flow (RBF) measurement was acquired using the circum-papillary double circular scan protocol of the RTVue system (Optovue Inc., Freemont, CA). The sample consisted of 17 healthy controls (group mean age 62±7 years; group mean NBP dip 14±8%); 17 POAG with normal NBP dip (age 66±9 years; NBP dip 11±5%), termed “dippers”; and 16 POAG with high NBP dip (age 64±7 years; NBP dip 24±5%), “over-dippers”. The NBP dip magnitude was calculated by taking the difference between mean arterial pressure (MAP) during the day and night while awake and asleep, respectively. Automated gas blender (RespiractTM, Thornhill Research Inc., Toronto) was used to stably provoke normoxic hypercapnia (15% increase in the end-tidal carbon dioxide partial pressure relative to homeostatic baseline). Six Doppler SDOCT RBF scans were acquired, during baseline and also during normoxic hypercapnia. RBF parameters were calculated and ANOVA was used to compare values between groups (p<0.05). Results: Total RBF at baseline was significantly different between the groups with controls being the highest (37.1±4.4mL/min), and over-dippers the lowest (29.6±9.0mL/min). Venous area showed significant differences at baseline between the groups with the lowest value in the over-dipper group, and the highest in the control group (39.9±7.0(x10-3)mm, and 46.6±6.6x(10-3)mm, respectively). Velocity was not significantly different between groups (p=0.27) at baseline. Breathing normoxic hypercapnia provoked an increase in flow that was significantly lower in the over-dipper group (1.0±8.6mL/min) and highest in the controls (8.2±10.8mL/min). Change in velocity was significantly different (p=0.02) between the groups, being highest in the control group (2.4±3.3mm/s) and lowest in the over-dipper group (-0.6±3.1mm/s). Venous area change was not significantly different between groups. Conclusions: Patients with POAG who exhibited an exaggerated nocturnal reduction in MAP also demonstrated lower baseline RBF values and an impeded retinal vascular response to normoxic hypercapnia, indicating greater vascular dysregulation in this group

Three-year Treatment Outcomes in the Ahmed Baerveldt Comparison Study

To compare three year outcomes and complications of the Ahmed FP7 Glaucoma Valve (AGV) and Baerveldt 101–350 Glaucoma Implant (BGI) for the treatment of refractory glaucoma

The relationship between retinal nerve fiber layer thickness and total retinal blood flow in primary open angle glaucoma.

Purpose: To investigate the relationship between Doppler SD-OCT derived retinal blood flow (RBF) and the retinal nerve fiber layer (RNFL) thickness in patients with primary open angle glaucoma (POAG) and healthy age-matched controls. Methods: Thirty three POAG patients (age, 65±8 years; Humphrey Field Analyzer, HFA, mean deviation, MD, -2.28±3.85) and 33 healthy controls (age, 63±5 years; HFA MD -0.48±1.56) were recruited. The Doppler SD-OCT retinal blood flow measurement was taken using the circum-papillary double circular scan protocol in the RTVue system (Optovue Inc., Freemont, CA, USA). A minimum of six RBF scans were acquired. Flow parameters were calculated only from the valid scans. Peri-papillary RNFL thickness was measured using RTVue’s RNFL scan protocol. Results: The total RBF in the POAG group was significantly lower than in the control group (group mean POAG RBF = 30.61±9.29mL/min; group mean control RBF = 40.68±11.32mL/min; p=<0.01). Superior and inferior RBF were also significantly lower in the POAG group (p=<0.01 for both superior & inferior RBF). The average RNFL thickness, superior and inferior RNFL thickness were significantly lower in the POAG group (p=<0.01). Linear regression analysis showed a significant positive correlation between the total RBF and average RNFL thickness (r=0.38, p=0.03), and the superior RBF and superior RNFL thickness (r=0.37, p=0.01). There was no correlation between the inferior RBF and RNFL thickness (r=0.30,p=0.09). Conclusions: There was an association between thinning of the RNFL and reduced inner retinal perfusion in the eyes of patients with POAG

Five-Year Treatment Outcomes in the Ahmed Baerveldt Comparison Study

To compare the five year outcomes of the Ahmed FP7 Glaucoma Valve (AGV) and the Baerveldt 101-350 Glaucoma Implant (BGI) for the treatment of refractory glaucoma

Retinal arteriolar vascular reactivity in untreated and progressive primary open-angle glaucoma

PURPOSE. To determine (1) the magnitude of retinal arteriolar vascular reactivity to normoxic hypercapnia in patients with untreated primary open-angle glaucoma (uPOAG) or progressive (p)POAG and in control subjects and (2) the effect of treatment with 2% dorzolamide on retinal vascular reactivity in uPOAG. METHODS. The sample comprised 11 patients with uPOAG (after undergoing treatment, they became treated (t)POAG), 17 patients with pPOAG (i.e., manifesting optic disc hemorrhage), and 17 age-similar control subjects. The partial pressure of end-tidal CO 2 (PETCO 2 ) was stabilized at 38 mm Hg at baseline. After baseline (10 minutes), normoxic hypercapnia was then induced (15 minutes) with an automated gas flow controller. Retinal arteriolar and optic nerve head (ONH) blood hemodynamics were assessed. The procedures were repeated after treatment with 2% dorzolamide for 2 weeks in tPOAG. RESULTS. Baseline arteriolar hemodynamics were not different across the groups. In control subjects, diameter, velocity, and flow increased (P Ͻ 0.001) in response to normoxic hypercapnia. There was no change in all three hemodynamic parameters to normoxic hypercapnia in uPOAG, whereas only blood flow increased (P ϭ 0.030) in pPOAG. Vascular reactivity was decreased in uPOAG and pPOAG patients compared with that in control subjects. After treatment with topical 2% dorzolamide for 2 weeks, the tPOAG group showed an increase in diameter, velocity, and flow (P Յ 0.04) in response to normoxic hypercapnia. Similar trends were noted for ONH vascular reactivity. CONCLUSIONS. A reduced magnitude of arteriolar vascular reactivity in response to normoxic hypercapnia was shown in uPOAG and in pPOAG. Vascular reactivity improved after dorzolamide treatment in POAG. (Invest Ophthalmol Vis Sci