Volume 12, Number 19
Monday, May 7, 2012


In this issue: (click heading to view article)
######### Two-Year Results of Ranibizumab and Bevacizumab in the Treatment of Neovascular AMD

######### Corneal Biomechanical Properties, CCT and IOP Across the Spectrum of Glaucoma
######### 24-Hour Heart Rate and Blood Pressure Variability in Patients with NTG
######### AMD and Long-Term Risk of Stroke
######### Briefly



Two-Year Results of Ranibizumab and Bevacizumab in the Treatment of Neovascular AMD

U.S. investigators conducted the following multicenter, randomized clinical trial to describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment.

They included 1,107 patients who were followed up during year 2 among 1,185 patients with neovascular age-related macular degeneration (AMD) who were enrolled in the clinical trial. At enrollment, they assigned patients to 4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment. The main outcome measure was mean change in visual acuity.

Among patients following the same regimen for 2 years, the investigators found that the mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, –1.4 letters; 95% confidence interval [CI], –3.7 to 0.8; p = 0.21). They also noted that the mean gain was greater for monthly than for as-needed treatment (difference, –2.4 letters; 95% CI, –4.8 to –0.1; p = 0.046) and that the proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, p = 0.0003; regimen, p < 0.0001). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (–2.2 letters; p = 0.03) and a lower proportion without fluid (–19%; p < 0.0001). The study investigators reported that rates of death and arteriothrombotic events were similar for both drugs (p > 0.60) and that the proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07–1.57; p = 0.009). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF).

According to the investigators, ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.

SOURCE: Martin DF, Maguire MG, Fine SL, et al.; Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) Research Group. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmol. 2011;May 2 [Epub ahead of print].


Corneal Biomechanical Properties, CCT and IOP Across the Spectrum of Glaucoma

This Indian prospective cross-sectional study evaluated corneal biomechanical properties across the glaucoma spectrum and studied the relationship between these measurements and intraocular pressure (IOP) measured by Goldmann applanation tonometry (GAT-IOP) and central corneal thickness (CCT).

The study, which took place at a tertiary-care teaching institute, included 323 eyes of 323 participants (71 normal, 101 glaucoma suspect [GS], 38 ocular hypertension [OHT], 59 primary angle-closure disease [PACD], 36 primary open-angle glaucoma [POAG], and 18 normal-tension glaucoma [NTG]) who had received no ophthalmic treatment. Corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated IOP (IOPcc), and Goldmann-correlated IOP (IOPg) measured by the Ocular Response Analyzer (ORA) were noted and GAT-IOP and CCT were recorded in all subjects. Main outcome measures included regression analysis used to determine the relationship between GAT-IOP, CCT, age, CRF and CH as well as Bland-Altman plots used to assess agreement between IOP measured by GAT and the ORA (IOPg).

It was reported that CH measurements were significantly less in POAG and NTG compared to normal subjects (p = .034 and p = .030 respectively), regardless of the IOP. It was also noted that the CRF was significantly less in NTG and maximum in POAG and OHT and regression analysis with CH as dependant variable showed significant association with GAT-IOP and CRF (p < .001) but not CCT, persisting on multivariate analysis (adjusted R2 = 0.483). Furthermore, GAT-IOP correlated strongly with Goldmann-correlated IOP on the ORA (IOPg) (r = 0.82; p < .001), but limits of agreement between the measurements were poor.

To conclude, CH and CRF may constitute a pressure-independent risk factor for glaucoma. CRF appears to influence GAT-IOP measurements more than simple geometric thickness measured by CCT. However, IOP measurements from the ORA are not interchangeable with, and are unlikely to replace, Goldmann applanation tonometry at the present time.

SOURCE: Kaushik S, Pandav SS, Banger A, et al. Relationship between corneal biomechanical properties, central corneal thickness, and intraocular pressure across the spectrum of glaucoma. Am J Ophthalmol. 2012;153(5):840–49.

24-Hour Heart Rate and Blood Pressure Variability in Patients with NTG

To define parameters of autonomic nervous system activity in patients with normal tension glaucoma (NTG), the authors of this study carried out ambulatory 24-h ECG and 24-h blood pressure (BP) monitoring in 54 patients with NTG (44 women, mean age 59.7) and 43 matched control subjects (34 women, mean age 57.0). They compared heart rate variability time and frequency domain parameters (low frequency (LF), high frequency (HF) and LF/HF ratio), BP variability (BPV), diurnal and nocturnal BP variables between study groups.

The authors noted that patients with NTG demonstrated higher LF, LF/HF and lower HF values than control subjects for the 24-h, daytime and night-time periods. They also found that the mean 24-h, daytime and night-time LF/HF ratios were statistically higher in patients with glaucoma as compared to control subjects (3.2±1.5 vs 2.2±0.8, p=0.0009), (3.5±1.7 vs 2.7±1.0, p=0.0173) and (2.6±1.7 vs 1.4±0.6, p=0.0001), respectively). The study authors found no statistical differences in the mean BP during the whole day, daytime and night-time, and in BPV (10.4±1.9 vs 10.5±2.1, p=0.790) between study groups. No difference was also found in the percentage decrease in night-time mean BP (12.3% vs 13.6%, p=0.720). Furthermore, ‘dippers’, ‘non-dippers’ and ‘overdippers’ with NTG showed significantly higher LF/HF ratio as compared to the same subgroups of control subjects.

The authors found that sympathovagal balance of autonomic nervous system in patients with NTG shifted towards sympathetic activity, however with no change of 24-h pattern of BPV as compared to controls.

SOURCE: Wierzbowska J, Wierzbowski R, Stankiewicz A, et al. Cardiac autonomic dysfunction in patients with normal tension glaucoma: 24-h heart rate and blood pressure variability analysis. Br J Ophthalmol. 2012;96(5):624–628.



AMD and Long-Term Risk of Stroke

Researchers examined the relationship of age-related macular degeneration (AMD) with incident stroke, including stroke subtypes of cerebral infarction and intracerebral hemorrhage and found that persons with AMD are at an increased risk of both cerebral infarction and intracerebral hemorrhage.

They included 12,216 participants with retinal photographs taken at the third examination visit (1993–1995) from the Atherosclerosis Risk in Communities (ARIC) Study, a population-based cohort study in middle-aged persons. They evaluated images for AMD signs according to a standardized protocol and identified and validated incident events of stroke and its subtypes through case record review over time.

The researchers diagnosed AMD in 591 participants, of whom 576 had early and 15 had late AMD. After a mean follow-up of 13.0 years (SD, 3.3), they noted that 619 persons developed an incident stroke, including 548 cerebral infarction and 57 intracerebral hemorrhages. Participants with any AMD were at an increased risk of stroke (multivariable adjusted hazard ratio, 1.51; 95% CI, 1.11–2.06) with a stronger association for intracerebral hemorrhage (hazard ratio, 2.64; 95% CI, 1.18–5.87) than cerebral infarction (hazard ratio, 1.42; 95% CI, 1.01–1.99), the researchers found.

These data provide further insight into common pathophysiological processes between AMD and stroke subtypes.

SOURCE: Ikram MK, Mitchell P, Klein R, et al. Age-related macular degeneration and long-term risk of stroke subtypes. JAHA. 2012; Apr 24. [Epub ahead of print].


  • ORAYA'S CLINICAL TRIAL FOR WET AMD ACHIEVES SUCESS. According to Oraya Therapeutics, Inc., the INTREPID clinical trial of radiation therapy has met its primary endpoint of reduction in anti-VEGF injections for patients with wet age-related macular degeneration (AMD). The study is the first sham-controlled double-masked trial to evaluate the effectiveness and safety of a one-time radiation therapy in conjunction with as-needed anti-VEGF injections for the treatment of wet AMD. Intended as a one-time procedure, the Oraya Therapy uses low-energy, highly targeted X-rays and is non-invasive, rapid, comfortable for the patient and easy for a trained operator to perform. Preliminary result analyses found no indication of radiation-related adverse events at the one-year trial end point. The IRay radiotherapy system is a CE marked medical device. In the United States it is limited by U.S. Federal law to Investigational Use. Click here to read more.
  • RPS RECEIVES CLIA WAIVER FOR ADENOPLUS. The FDA has announced that Rapid Pathogen Screening's (RPS) AdenoPlus has been granted waived status under the Clinical Laboratory Improvement Amendments (CLIA). AdenoPlus is an improved version of RPS's first point-of-care diagnostic test for conjunctivitis. Being granted this waiver classifies AdenoPlus as a low complexity device, which allows medical office personnel to administer the test. Additionally, being granted the waiver, in addition to FDAS 510(k) clearance that this next-generation product previously received, enables AdenoPlus to be used throughout the United States. Click here to find out more.
  • KAMRA CORNEAL INLAY NOW AVAILABLE TO KOREAN MARKET. AcuFocus has received approval from the Korean Food and Drug Administration (KFDA) for its KAMRA corneal inlay, which is designed to only permit focused light rays to enter the eye, allowing patients to see near and intermediate objects more clearly without glasses. The KAMRA inlay has been implanted in more than 11,000 patients and is now available in 35 countries worldwide. It has received CE mark for use in the European Union and is an investigational device under FDA Investigational Device Exemption (IDE) in the United States. Visit http://kamrainlay.com to learn more.


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