Review of Ophthalmology Online Review of Ophthalmology Online

Volume 13, Number 49
Monday, December 9, 2013

In this issue: (click heading to view article)
######### Treatment of PCV with a Combination of PDT and Intravitreal Bevacizumab

######### A Closer Look at RNFL Progression in Glaucoma

######### Mineralocorticoid Receptor Antagonism in the Treatment of Chronic CSC
######### PCV in Caucasian Patients with Presumed Neovascular AMD and Poor Ranibizumab Response
######### Briefly


Treatment of PCV with a Combination of PDT and Intravitreal Bevacizumab

The following retrospective, observational study evaluated the long-term visual outcome following combination therapy of photodynamic therapy (PDT) with intravitreal bevacizumab injections for polypoidal choroidal vasculopathy (PCV).

The medical records of 34 eyes (34 patients) with naïve PCV who were treated with combination therapy were analyzed. All patients completed at least three years of follow-up and all clinical data, including age, best-corrected visual acuity (BCVA, logarithm of the minimum angle resolution [logMAR]), imaging data of fluorescein angiography, indocyanine green angiography and optical coherence tomography, were investigated.

During a mean follow-up period of 46.82 ± 5.22 months, means of 1.44 ± 0.71 times of PDT and 9.18 ± 6.61 intravitreal bevacizumab injections were performed. During follow-up, 21 eyes (61.8%) showed at least one recurrence. It was noted that mean BCVA was 0.59 ± 0.35 logMAR (20/77 Snellen equivalent) at baseline, and 0.39 ± 0.34 logMAR (20/49 Snellen equivalent) at three years (p=0.004). At three years, it was reported that 14 patients (41.2%) gained 0.3 logMAR or more BCVA, and four patients (11.8%) lost 0.3 logMAR or more BCVA than baseline. Baseline polyp size (B=0.551; p=0.005) and location of polyps (B=–0.400; p=0.033) were significantly correlated with long-term visual outcome after combination therapy for PCV.

Combination therapy of PDT with intravitreal bevacizumab injections showed favorable visual outcomes, and significant visual improvement was maintained in PCV patients. A total of 88.2% of patients avoided visual loss at three years after treatments. Largest polyp size at baseline and location of polypoidal lesions were prognostic factors for long-term visual outcomes in these patients.

SOURCE: Kang HM, Koh HJ, Lee CS, Lee SC. Combined photodynamic therapy with intravitreal bevacizumab injections for polypoidal choroidal vasculopathy: long-term visual outcome. Am J Ophthalmol. 2013;Nov 25. [Epub ahead of print].

A Closer Look at RNFL Progression in Glaucoma

To investigate the performance of spectral-domain optical coherence tomography (SD-OCT) and scanning laser polarimetry in the detection of progressive retinal nerve fiber layer (RNFL) changes and to determine whether reduction of the RNFL retardance occurred before thinning of the RNFL in glaucoma, researchers performed a prospective, longitudinal study that included 184 eyes of 116 glaucoma patients and 43 normal eyes of 23 healthy individuals.

They followed up with patients every four months for at least 36 months with RNFL retardance (GDx Enhanced Corneal Compensation; Carl Zeiss Meditec) and RNFL thickness (Cirrus HD-OCT; Carl Zeiss Meditec) measured in the same visit. They evaluated progressive RNFL retardance and thickness changes with event-based analysis (Guided Progression Analysis; Carl Zeiss Meditec) with reference to the RNFL retardance change map and the RNFL thickness change map, respectively. Additionally, the area and frequency distribution of RNFL changes were examined by overlaying the RNFL retardance change maps and the RNFL thickness change maps in the latest follow-up. The researchers evaluated the agreement of RNFL retardance and RNFL thickness progression with κ statistics. The main outcome measure was the number of eyes with progressive RNFL changes over time.

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: Xu G, Weinreb RN, Leung CK. Retinal nerve fiber layer progression in glaucoma: a comparison between retinal nerve fiber layer thickness and retardance. Ophthalmology. 2013;120(12):2493–2500.


Mineralocorticoid Receptor Antagonism in the Treatment of Chronic CSC

Based on experimental data showing that central serous chorioretinopathy (CSC) could result from overactivation of mineralocorticoid receptor pathway in choroid vessels, the authors of the following nonrandomized pilot study examined eplerenone, a mineralocorticoid receptor antagonist, as a potential treatment for CSC.

The study included 13 patients with CSC of at least four-month duration, treated with 25 mg/day of oral eplerenone for a week followed by 50 mg/day for one or three months. The primary outcome measure was the changes in central macular thickness recorded by optical coherence tomography (OCT), and the secondary outcomes included changes in foveal subretinal fluid (SRF) measured by OCT, in best-corrected visual acuity (BCVA) and the percentage of eyes achieving complete resolution of subretinal fluid during the treatment period.

According to the authors, central macular thickness decreased significantly from 352 ± 139 µm at baseline to 246 ± 113 µm and 189 ± 99 µm at one and three months under eplerenone treatment (p<0.05 and p<0.01, respectively). They noted that at three months, the subretinal fluid significantly decreased compared with baseline subretinal fluid (p<0.01) and BCVA significantly improved compared with baseline BCVA (p<0.001).

To conclude, eplerenone treatment was associated with a significant reduction in central macular thickness, subretinal fluid level and an improvement in visual acuity. Randomized controlled trials are needed to confirm these encouraging results.

SOURCE: Bousquet E, Beydoun T, Zhao M, et al. Mineralocorticoid receptor antagonism in the treatment of chronic central serous chorioretinopathy: a pilot study. Retina. 2013;33(10)2096–2102.


PCV in Caucasian Patients with Presumed Neovascular AMD and Poor Ranibizumab Response

Swiss investigators sought to determine the prevalence of polypoidal choroidal vasculopathy (PCV) in patients with presumed neovascular age-related macular degeneration (AMD) who were considered poor responders to ranibizumab.

They retrospectively included Caucasian patients with suspected neovascular AMD, presumed to be choroidal neovascularisation, previously treated with ≥8 intravitreal injections of ranibizumab 0.5 mg (Lucentis; Novartis AG) administered as required during optical coherence tomography-guided dosing. The investigators categorized eyes according to the time from injection one to injection six (group one: <12 months; group two: ≥12 months). They used indocyanine green angiography (ICGA) to re-evaluate eyes for PCV and suitable candidates received reduced-fluence photodynamic therapy/ranibizumab combination therapy supplemented by ranibizumab monotherapy, as required.

A total of 202 eyes were included (group one: 73.8%; group two: 26.2%). The study investigators reported that the prevalence of PCV in group one (21.5%) was significantly higher than in group two (3.8%; p=0.003). They also noted that after initiation of combination therapy, 16 eyes with PCV received 3.1 ± 2.5 ranibizumab injections/year vs. 8.4 ± 2.4 injections/year before initiation of combination therapy (p<0.001).

To conclude, in Caucasian patients with presumed neovascular AMD, PCV prevalence is increased in eyes that respond poorly to ranibizumab monotherapy. ICGA improved PCV diagnosis in poor responders; combination therapy may be beneficial for eyes with PCV.

SOURCE: Hatz K, Prünte C. Polypoidal choroidal vasculopathy in Caucasian patients with presumed neovascular age-related macular degeneration and poor ranibizumab response. Br J Ophthalmol. 2013; Nov 18. [Epub ahead of print].

  • OPHTHALMOLOGY AND OPTOMETRY FORM PARTNERSHIP TO BENEFIT DOCTORS AND PATIENTS. The American Academy of Ophthalmology and the American Academy of Optometry have announced a joint initiative to work together to better prepare and support their members in delivering the highest quality eye care. The two organizations are engaging with each other in an effort to foster a mutual approach to serving a growing population of patients in the United States who are expected to require eye-health services in the near future. By working together, the two organizations anticipate being better positioned to assist their respective members in being able to efficiently manage the rapidly growing demand for eye care due to many chronic eye diseases increasing in prevalence in the United States related to the aging baby boomer population. They also expect that healthcare reform will result in a significant increase in the number of Americans seeking eye care. The academies are jointly informing their respective memberships to ensure that their members are aware of this collaborative strategic effort and have an opportunity to provide feedback to the organizations as they begin to create educational opportunities. The organizations anticipate that these programs will be developed over the next 12 to 18 months with a formal launch in 2015.
  • RESULTS ANNOUNCED FOR PHASE III STUDY INVESTIGATING LIFITEGRAST IN ADULTS WITH DRY EYE DISEASE. Shire plc has announced top-line results from OPUS-2, a Phase III efficacy and safety study of 5.0% lifitegrast ophthalmic solution. Lifitegrast is a small-molecule integrin antagonist designed to treat dry eye disease. According to Shire, OPUS-2 compared lifitegrast to placebo administered twice daily for 84 days (12 weeks) in dry eye patients with history of active artificial tear use within 30 days prior to screening. Lifitegrast met the prespecified co-primary endpoint for the patient-reported symptom of eye dryness (change in Eye Dryness Score from baseline to week 12) (p value <0.0001). However, lifitegrast did not meet the prespecified co-primary endpoint for the sign of inferior corneal staining score (change from baseline to week 12) using fluorescein staining compared with placebo (p value=0.6186). There were no ocular serious treatment-emergent adverse events or drug-related serious treatment-emergent adverse events. For additional information on the lifitegrast Phase III clinical development program, click here.
  • FDA GRANTS PRIORITY REVIEW STATUS FOR AVEDRO'S CORNEAL CROSS-LINKING NDA. Avedro Inc. received notification recently from the FDA stating that its New Drug Application (NDA) for riboflavin ophthalmic solution/KXL system has been filed and granted priority review status, placing the application action date at March 15, 2014. The proposed indications of treatment of keratoconus and corneal ectasia following refractive surgery are both orphan indications and if approved, riboflavin ophthalmic solution/KXL system would be the first FDA-approved therapeutic treatment for them. Orphan-drug designation is granted by the FDA Office of Orphan Products Development to promote the development of new therapies for rare diseases and disorders affecting fewer than 200,000 individuals in the United States. If approved, Avedro would receive seven years of commercial exclusivity in the United States. Click here for additional information.
  • STEM CELL PROTEIN MAY HOLD HOPE FOR STAVING OFF PERMANENT VISION LOSS. A recent press release reports that a team of researchers from Gifu Pharmaceutical University and Gifu University in Japan has published results demonstrating that a type of protein found in stem cells taken from adipose tissue can reverse and prevent age-related, light-induced retinal damage in a mouse model, offering hope for those faced with permanent vision loss. The research, published in the latest issue of STEM CELLS Translational Medicine, has proven that a single injection of adipose-derived stem cells (ASCs) reduced the retinal damage induced by light exposure in mice and found that adipose-derived stem cells in conditioned medium inhibited the retinal damage by hydrogen peroxide and visible light both in the medium and in live mice. The research also revealed that a type of protein called progranulin found in the ASCs might be what plays the pivotal role in protecting against light-induced eye damage.
  • JETREA'S PERMANENT J-CODE EFFECTIVE JANUARY 1ST. Centers for Medicare & Medicaid Services (CMS) has published the permanent Healthcare Common Procedure Coding System (HCPCS) code for Jetrea (ocriplasmin)—J7316)—according to ThromboGenics NV. The company believes that the permanent J-Code will streamline the reimbursement process for retina practices and instill higher reimbursement confidence. Read more at
  • NICE PUBLISHES FINAL GUIDANCE ON ILUVIEN. The United Kingdom's National Institute for Health and Care Excellence (NICE) has published final guidance for Alimera Science's sustained-release intravitreal implant Iluvien, clearing the path to patient availability through the National Health Service. Iluvien is used to treat vision impairment associated with chronic diabetic macular edema considered insufficiently responsive to available therapies, and now patients who have a pseudophakic eye will have greater access to the implant for treatment of the condition. Get the full scoop here.
  • SANTEN LAUNCHES NEW TOPICAL ANTI-ALLERGIC AGENT IN JAPAN. Santen Pharmaceutical Co., Ltd. obtained the rights from Nippon Boehringer Ingelheim Co., Ltd. (Tokyo) to develop Alesion 0.05% Ophthalmic Solution (epinastine HCl) in Japan as an effective treatment for allergic conjunctivitis and has just launched the product. Japanese clinical trials demonstrated that epinastine HCl blocks histamine H1 receptors and inhibits the release of chemical mediators from mast cells, which in turn alleviates ocular itching and hyperemia. No serious ocular or systemic adverse drug reactions were observed in these clinical studies. Read more at


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