Review of Ophthalmology Online Review of Ophthalmology Online

Volume 13, Number 50
Monday, December 16, 2013

In this issue: (click heading to view article)
######### Ranibizumab Use in Patients with CNV Secondary to Pathologic Myopia

######### SLT's Effect on Aqueous Humor Dynamics in Patients with Ocular Hypertension and POAG

######### Secondary Analyses of the Effects of Lutein/Zeaxanthin on AMD Progression
######### Risk of Parkinson's Disease Following Diagnosis of Neovascular AMD
######### Briefly


Ranibizumab Use in Patients with CNV Secondary to Pathologic Myopia

In the following Phase III, 12-month, randomized, double-masked, multicenter, active-controlled study, investigators compared the efficacy and safety of ranibizumab 0.5 mg, guided by visual acuity (VA) stabilization or disease activity criteria, versus verteporfin photodynamic therapy (vPDT) in patients with visual impairment due to myopic choroidal neovascularization (CNV).

The study included 277 patients with visual impairment due to myopic CNV and the investigators randomized patients to receive ranibizumab on day one, month one and thereafter as needed guided by VA stabilization criteria (group one, n=106); ranibizumab on day one and thereafter as needed guided by disease activity criteria (group two, n=116); or vPDT on day one and disease activity treated with ranibizumab or vPDT at investigators' discretion from month three (group three, n=55). The main outcome measure was mean average best-corrected visual acuity (BCVA) change from baseline to month one through months three (primary) and six, mean BCVA change and safety over 12 months.

According to the investigators, ranibizumab treatment in groups one and two was superior to vPDT based on mean average BCVA change from baseline to month one through month three (group one: +10.5, group two: +10.6 vs. group three: +2.2 Early Treatment Diabetic Retinopathy Study [ETDRS] letters; both p<0.0001). They also observed that ranibizumab treatment guided by disease activity was noninferior to VA stabilization-guided retreatment based on mean average BCVA change from baseline to month one through month six (group two: +11.7 vs. group one: +11.9 ETDRS letters; p<0.00001). Mean BCVA change from baseline to month 12 was +13.8 (group one), +14.4 (group two) and +9.3 ETDRS letters (group three). At month 12, 63.8% to 65.7% of patients showed resolution of myopic CNV leakage. Patients received a median of 4.0 (group one) and 2.0 (groups two and three) ranibizumab injections over 12 months. No deaths or cases of endophthalmitis and myocardial infarction occurred.

Ranibizumab treatment, irrespective of retreatment criteria, provided superior BCVA gains versus vPDT up to month three, the investigators found. Ranibizumab treatment guided by disease activity criteria was noninferior to VA stabilization criteria up to month six. Over 12 months, individualized ranibizumab treatment was effective in improving and sustaining BCVA and was generally well-tolerated in patients with myopic CNV.

SOURCE: Wolf S, Balciuniene VJ, Laganovska G, et al; RADIANCE Study Group. RADIANCE: a randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia. Ophthalmology. Dec 9. [Epub ahead of print].

SLT's Effect on Aqueous Humor Dynamics in Patients with Ocular Hypertension and POAG

To examine the effect of primary selective laser trabeculoplasty (SLT) on outflow facility and aqueous flow rate in patients with primary open-angle glaucoma (POAG) or ocular hypertension, researchers included 18 eyes (nine with ocular hypertension and nine with POAG) this prospective, noncontrolled study. They treated patients with intraocular pressures (IOPs) >21 to 35 mmHg with 360-degree SLT after a baseline measurement of IOP, tonographic outflow facility and morning aqueous humor production. They also used electronic SchiØtz tonography to measure the outflow facility. Additionally, they measured the aqueous flow rate by fluorophotometry, and used a pneumotonometer to measure the IOP. They repeated all measurements at least three months after the laser therapy. Furthermore, they used paired Student t tests to compare aqueous dynamics parameters before and after treatment.

The mean age of the study population was 56.7 ± 12.4 years. The study researchers noted that the IOP decreased significantly (21%) from 24.0 ± 3.0 to 18.9 ± 2.7 mm Hg (p<0.001), whereas tonographic outflow facility increased significantly (55.5%) from 0.09 ± 0.05 to 0.14 ± 0.08 µL/min/mm Hg (p=0.003) three months after laser treatment. No statistically significant changes in the production of aqueous humor were found (p=0.46).

They collected and reviewed 2,472 OCT thickness maps and 2,472 RNFL retardance maps with a mean follow-up of 55.1 months. They noted that 27 eyes (14.6%; 26 glaucoma patients) showed progressive RNFL thinning, whereas eight eyes (4.3%; eight glaucoma patients) showed progressive reduction of RNFL retardance. The study researchers also noted that seven eyes (3.8%; seven glaucoma patients) had progression that was detected by both instruments, all with progressive RNFL thinning detected before progressive reduction of RNFL retardance became evident, and the mean lag time was 13.4 months (range, 4.0 to 37.6 months). The agreement between RNFL thickness and RNFL retardance progression was fair (κ, 0.357). The researchers noted progressive loss of RNFL thickness most frequently at the inferotemporal 223° to 260°, whereas the inferotemporal 227° to 263° and superior 56° to 117° were observed most commonly for progressive loss of RNFL retardance. In the normal group, no eyes showed reduction in RNFL thickness or retardance.

At a comparable level of specificity, progressive RNFL thinning was detected more often than progressive reduction of RNFL retardance. For eyes with progressive loss of RNFL thickness and RNFL retardance, the former preceded the latter.
SOURCE: Beltran-Agullo L, Alaghband P, Obi A, et al. The effect of selective laser trabeculoplasty on aqueous humor dynamics in patients with ocular hypertension and primary open-angle glaucoma. J Glaucoma. 2013;22(9):746–749.


Secondary Analyses of the Effects of Lutein/Zeaxanthin on AMD Progression

The Age-Related Eye Disease Study (AREDS) formulation for the treatment of age-related macular degeneration (AMD) contains vitamin C, vitamin E, beta-carotene and zinc with copper. The Age-Related Eye Disease Study 2 (AREDS2) assessed the value of substituting lutein/zeaxanthin in the AREDS formulation because of the demonstrated risk for lung cancer from beta-carotene in smokers and former smokers and because lutein and zeaxanthin are important components in the retina.

The purpose of this study was to further examine the effect of lutein/zeaxanthin supplementation on progression to late AMD. The AREDS2 is a multicenter, double-masked randomized trial of 4,203 participants, aged 50 to 85 years, at risk for developing late AMD; 66% of patients had bilateral large drusen and 34% had large drusen and late AMD in one eye. In addition to taking the original or a variation of the AREDS supplement, participants were randomly assigned in a factorial design to one of the following four groups: placebo; lutein/zeaxanthin, 10 mg/2 mg; omega-3 long-chain polyunsaturated fatty 3 acids, 1.0 g; or the combination. Documented development of late AMD by central, masked grading of annual retinal photographs or by treatment history was the main outcome and measure.

In exploratory analysis of lutein/zeaxanthin vs. no lutein/zeaxanthin, the hazard ratio of the development of late AMD was 0.90 (95% CI, 0.82 to 0.99; p=0.04). Exploratory analyses of direct comparison of lutein/zeaxanthin vs. beta-carotene showed hazard ratios of 0.82 (95% CI, 0.69 to 0.96; p=0.02) for development of late AMD, 0.78 (95% CI, 0.64 to 0.94; p=0.01) for development of neovascular AMD, and 0.94 (95% CI, 0.70 to 1.26; p=0.67) for development of central geographic atrophy (GA). In analyses restricted to eyes with bilateral large drusen at baseline, the direct comparison of lutein/zeaxanthin vs. beta-carotene showed hazard ratios of 0.76 (95% CI, 0.61 to 0.96; p=0.02) for progression to late AMD, 0.65 (95% CI, 0.49 to 0.85; p=0.002) for neovascular AMD, and 0.98 (95% CI, 0.69 to 1.39; p=0.91) for central GA.

The totality of evidence on beneficial and adverse effects from AREDS2 and other studies suggests that lutein/zeaxanthin could be more appropriate than beta-carotene in the AREDS-type supplements.

SOURCE: The Age-Related Eye Disease Study 2 (AREDS2) Research Group. Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression. JAMA Ophthlamol. Dec 5. [Epub ahead of print].

Risk of Parkinson's Disease Following Diagnosis of Neovascular AMD

The authors of the following retrospective matched-cohort study investigated the risk for Parkinson's disease during a three-year follow-up period after a diagnosis of neovascular age-related macular degeneration (AMD) using a nationwide population-based dataset in Taiwan.

They identified 877 subjects with neovascular AMD as the study cohort and randomly selected 8,770 subjects for a comparison cohort. They individually followed each subject for a three-year period to identify those who subsequently developed Parkinson's disease. The authors performed stratified Cox proportional hazard regressions as a means of comparing the three-year risk of subsequent Parkinson's disease between the study and comparison cohorts.

They reported that the incidence rate of Parkinson's disease was 5.32 (95% confidence interval [CI]: 3.03 to 8.72) per 1,000 person-years in patients with neovascular AMD and 2.09 (95% CI: 1.59 to 2.70) per 1,000 person-years in comparison patients. The log-rank test indicated that subjects with neovascular AMD had a significantly lower three-year Parkinson's disease-free survival rate than comparison subjects (p<0.001). After censoring cases in which patients died during the follow-up period and adjusting for monthly income, geographic region, hypertension, diabetes, hyperlipidemia and coronary heart disease, the hazard ratio of Parkinson's disease during the three-year follow-up period for subjects with neovascular AMD was 2.57 (95% CI: 1.42 to 4.64) that of comparison subjects.

In conclusion, in this study, the authors found subjects with neovascular AMD to be at a significant risk of Parkinson's disease during a three-year follow-up period after their diagnosis among Taiwanese Chinese. Further study is needed to confirm our findings and explore the underlying pathomechanism.

SOURCE: Chung SD, Ho JD, Hu CC, et al. Increased risk of Parkinson Disease following a diagnosis of neovascular age-related macular degeneration: a retrospective cohort study. Am J Ophthalmol. Dec 5. [Epub ahead of print].

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