Volume 13, Number 5
Monday, February 4, 2013


In this issue: (click heading to view article)
######### Automated AMD Severity Classification Using Fundus Photographs

######### Link Between Aqueous VEGF and Endothelin-1 Levels in BRVO Associated with NTG
######### A Look at Seasonal Changes in VF Sensitivity and IOP
######### Clinical Characteristics in Korean vs. Western NTG Patients
######### Briefly



Automated AMD Severity Classification Using Fundus Photographs

The authors of this study evaluated an automated analysis of retinal fundus photographs to detect and classify severity of age-related macular degeneration (AMD) compared with grading by the Age-Related Eye Disease Study (AREDS) protocol.

Following approval by the Johns Hopkins University School of Medicine's Institution Review Board, digitized images of field two (macular) fundus photographs from AREDS obtained over a 12-year longitudinal study were classified automatically using a visual words method to compare with severity by expert graders.

According to the authors, sensitivities and specificities, respectively, of automated imaging, when compared with expert fundus grading of 468 patients and 2,145 fundus images are: 98.6% and 96.3% when classifying categories one and two versus category three; 98.6% and 95.7% when classifying category one vs. category three; 96.0% and 94.7% when classifying category one vs. categories three and four.

To conclude, development of an automated analysis for classification of AMD from digitized fundus photographs has high sensitivity and specificity when compared with expert graders and may have a role in screening or monitoring.

SOURCE: Kankanahalli S, Burlina PM, Wolfson Y, et al. Automated classification of severity of age-related macular degeneration from fundus photographs. Invest Ophthalmol Vis Sci. 2013; Jan 29. [Epub ahead of print].


Link Between Aqueous VEGF and Endothelin-1 Levels in BRVO Associated with NTG

To evaluate aqueous levels of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) in patients with branch retinal vein occlusion (BRVO) with and without normal tension glaucoma (NTG), and to assess the therapeutic efficacy of intravitreal bevacizumab (IVB) in these patients, researchers followed 16 eyes with NTG of 48 age- and sex-matched eyes without NTG that had previously received IVB for BRVO for six months.

They measured aqueous VEGF and ET-1 levels by enzyme-linked immunosorbent assay at the time of baseline IVB as well as logarithm of the minimum angle of resolution, best corrected visual acuity (BCVA) and central macular thickness (CMT) at baseline and then at one, three and six months post-injection.

The obstruction site of BRVO was closer to the optic disk in eyes with NTG compared with controls (p=0.001), the researchers noted. They found that baseline BCVA, CMT and VEGF levels were similar between the two groups and that baseline ET-1 levels were significantly higher in eyes with NTG than those without NTG (p=0.009). After IVB, the study authors also observe a significant improvement in both BCVA and CMT at six months, irrespective of the presence of NTG. However, BCVA in the presence of NTG was significantly worse at six months compared with eyes without NTG even though CMT was similarly reduced in both groups (p=0.04).

Aqueous VEGF levels are similar in patients with BRVO with or without NTG, whereas aqueous ET-1 levels are elevated in the presence of NTG. Although IVB may be effective in the treatment of BRVO, the presence of NTG may limit visual recovery despite anatomic recovery of CMT.

SOURCE: Sin BH, Song BJ, Park SP. Aqueous vascular endothelial growth factor and endothelin-1 levels in branch retinal vein occlusion associated with normal tension glaucoma. J Glaucoma. 2013;22(2):104–109.

A Look at Seasonal Changes in VF Sensitivity and IOP

Longitudinal testing plays a key role in glaucoma management and variability between visits hampers the ability to monitor progression. It has previously been shown that average intraocular pressure (IOP) exhibits seasonal fluctuations. This comparative case series examines whether visual field (VF) sensitivity also exhibits seasonal fluctuations and seeks to determine whether such fluctuations are correlated to seasonal IOP effects.

This study looked at 33,873 visits by 1,636 participants enrolled in the Ocular Hypertension Treatment Study (OHTS). Participants were split into six geographic zones according to the prevailing climate in their location. At each visit, standard automated perimetry was conducted on each eye, and IOP was measured. With regard to main outcome measures, mixed effects regression models were formed to look for sinusoidal periodic effects on the change in perimetric mean deviation since the last visit (ΔMD) and on IOP, both overall and within each zone.

When all the data were included, a significant seasonal effect on (ΔMD was found with magnitude 0.06 dB, peaking in February (p<0.001). It was reported that five of the six geographic zones exhibited significant seasonal effects on ΔMD, peaking between January and April, with magnitudes ranging from 0.04 dB (p=0.049) to 0.21 dB (p<0.001). Zones with greater climactic variation showed larger seasonal effects on ΔMD. Furthermore, all six zones exhibited a seasonal effect on IOP, peaking in January or February, with magnitudes ranging from 0.14 to 0.39 mmHg (p≤0.02 in all cases). However, there was no evidence of a significant association between the magnitudes or dates of peaks of the two seasonal effects.

In conclusion, the mean deviation was significantly higher in winter than in summer. There is no evidence of an association with seasonal IOP fluctuations and the cause of the seasonal effect on visual field sensitivity is unknown. These findings may help shed light on the glaucomatous disease process and aid efforts to reduce test–retest variability.

SOURCE: Amparo F, Sadrai Z, Jin Y, et al. Safety and efficacy of the multitargeted receptor kinase inhibitor pazopanib in the treatment of corneal neovascularization. Invest Ophthalmol Vis Sci. 2013;54(1):537–544.

Clinical Characteristics in Korean vs. Western NTG Patients

Investigators conducted the following retrospective, cross-sectional study to detect potential differences in the phenotypes between Western normal-tension glaucoma (NTG) and Korean NTG.

They studied 184 NTG eyes of 71 patients of the Jules Stein Eye Institute, University of California, Los Angeles, and 113 patients of the Seoul National University Hospital, Seoul, Korea, after reviewing the medical charts. All eligible patients from both institutions who were evaluated between July 2007 and June 2008 were included. The groups were matched for stage of glaucoma severity based on the visual field (VF) mean deviation value. All patients underwent a complete ophthalmic examination, Humphrey perimetry, Heidelberg Retina Tomography, Stratus optical coherence tomography and pachymetry. Additionally, the investigators compared structural and functional parameters between the two groups.

They reported no statistically significant differences in the baseline intraocular pressure, disc area, frequency of disc hemorrhage or peripapillary atrophy (p>.05). They also found that cup-shape measure (by Heidelberg Retina Tomography), average RNFL thickness (by Stratus optical coherence tomography) and central corneal thickness were significantly different (p<.002). The investigators noted that eyes of Korean NTG patients showed higher values for cup-shape measure, higher average RNFL thicknesses and thinner central corneal thicknesses than Western NTG patients. The difference was significant (p<.001) while controlling for age, sex, disc area, mean deviation, pattern standard deviation and spherical equivalent with multivariate analysis.

Korean NTG patients showed steeper cup shapes, thicker RNFL thickness and thinner central corneal thickness compared with Western NTG patients with similar amounts of visual field loss. This result may help clinicians understand the clinical characteristics of NTG patients and points to the heterogeneous character of the glaucomas.

SOURCE: Kim JM, Jeoung JW, Bitrian E, et al. Comparison of clinical characteristics between Korean and Western normal-tension glaucoma patients. Am J Ophthalmol. 2013; Jan 24. [Epub ahead of print].

  • BAUSCH + LOMB COMPLETES ACQUISITION OF TECHNOLAS PERFECT VISION, INITIATES PHASE III PROGRAM FOR GLAUCOMA DRUG CANDIDATE. In a recent press release, Bausch + Lomb reported that it completed its acquisition of Technolas Perfect Vision GmbH and that the new entity will be known as Bausch + Lomb Technolas. The Technolas Perfect Vision team will become part of Bausch + Lomb's surgical business, and its femtosecond and excimer laser platforms for cataract and refractive surgery will join the company's existent product portfolio and new product pipeline. Kristian Hohla, PhD, chief executive officer of Technolas Perfect Vision, will serve as the president of Bausch + Lomb Technolas, reporting to John Barr in the surgical business of Bausch + Lomb.

    In other news, Bausch + Lomb has initiated its Phase III clinical program of latanoprostene bunod (previously known as BOL-303259-X and NCX 116) for the reduction of intraocular pressure (IOP) in patients with glaucoma or ocular hypertension. Latanoprostene bunod is a nitric oxide-donating prostaglandin F2 alpha analog licensed by Nicox to Bausch + Lomb. This pivotal Phase III program includes two separate randomized, multicenter, double-masked, parallel-group clinical studies, APOLLO and LUNAR, designed to compare the efficacy and safety of latanoprostene bunod administered once-daily with timolol maleate 0.5% administered twice daily in lowering IOP in patients with open-angle glaucoma or ocular hypertension. Read more at www.bausch.com.
  • SANTEN AND CLEARSIDE ENTER INTO AGREEMENTS FOR POSTERIOR OCULAR DISEASE. Santen Inc. and Clearside Biomedical Inc. recently announced that Santen Ltd, the parent company of Santen Inc., has made an investment in Clearside Biomedical Inc. and has also entered into a research collaboration agreement for posterior ocular diseases. Santen will join with other investors to fund an additional $7.9 million for continued development of CLS1001 (triamcinolone acetonide) Suprachoroidal Injectable Suspension into pivotal testing and to further Clearside Biomedical's pipeline in ocular choroidal neovascularization and inflammatory diseases of the posterior segment. The FDA has allowed Clearside Biomedical to pursue testing related to the company's Investigational New Drug (IND) Application for CLS1001, which would treat sympathetic ophthalmia, temporal arteritis, uveitis and ocular inflammatory conditions unresponsive to topical corticosteroids. Clinical testing is scheduled to proceed in the first quarter of 2013. Click here for additional information.

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