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Volume 11, Number 50
Monday, December 12, 2011
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In this issue: (click heading to view article)
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######### New and Established AMD Susceptibility Genes in Women

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######### Incidence of Post-op Endophthlamitis Following Immediate Sequential Bilateral Cataract Surgery
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######### Circulation of Neural Stem/Progenitor Cells in Peripheral Blood of Patients with Neovascular AMD
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######### Differences in Topography Between Large and Normal Optic Discs
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New and Established AMD Susceptibility Genes in Women

The authors of this multicenter case-control study assessed whether established and newly reported genetic variants, independent of known lifestyle factors, are associated with the risk of age-related macular degeneration (AMD) among women participating in the Women's Health Initiative Sight Exam (WHI-SE) Genetic Ancillary Study.

A total of 146 women with intermediate and late stages of AMD and 1,269 subjects without AMD underwent ocular examinations and fundus photography to determine stage of AMD. Using logistic regression analysis, the study authors assessed 14 polymorphisms at or near 11 genes, including previously confirmed genes CFH, ARMS2/HTRA1, C2, C3 and CFI; recently reported AMD genes in the high-density lipoprotein cholesterol (HDL) pathway LIPC, ABCA1, CETP and LPL; TIMP3/SYN3, a known ocular gene recently linked with AMD; and APOE.

After adjusting for demographic, behavioral and other genetic factors, the authors detected a protective effect among TT carriers compared with non-carriers for the HDL pathway gene, LIPC rs493258, for intermediate and late AMD (OR [95% confidence interval]: 0.3 [0.2–0.7], p=.003). They determined that variants in CFH rs1410996, ARMS2/HTRA1 A69S and C3 R102G were significantly associated with an increased risk of AMD. They also noted that individuals with the homozygous CFI rs10033900 TT genotype had a 2.9 [1.2–7.2]-fold increased risk, and those with the CFH Y402H GG genotype had a 2.2 [1.0–4.8]-fold higher risk of developing AMD compared with non-carriers. The authors believe that APOE4 carriers may have a reduced risk of intermediate/late AMD (OR = 0.5 [0.3–0.9], p=.015. They also saw suggestive associations between AMD and the HDL pathway genes CETP and LPL.

In this unique national cohort of women, the study authors found associations with established AMD-related genetic factors and the recently reported LIPC gene in the HDL pathway. These findings may help develop novel therapeutic targets to treat or delay the onset of the disease.

SOURCE: Peter I, Huggins GS, Ordovas JM, et al. Evaluation of new and established age-related macular degeneration susceptibility genes in the Women's Health Initiative Sight Exam (WHI-SE) Study. Am J Ophthalmol. 2011;152(6):1005–1013.



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Incidence of Post-op Endophthlamitis Following Immediate Sequential Bilateral Cataract Surgery

Investigators at the Eye Foundation of Canada, Toronto, Ontario, Canada, sought to determine a best estimate of the incidence of endophthalmitis after immediately sequential bilateral cataract surgery (ISBCS) and assess the benefit of prophylactic intracameral antibiotics.

In their cohort study, they performed a detailed literature search to obtain recently reported frequencies of postoperative endophthalmitis with or without the use of prophylactic intracameral antibiotics. They surveyed members of the International Society of Bilateral Cataract Surgeons and collected the data to determine the results of unilateral and bilateral cataract surgeries performed by experienced bilateral cataract surgeons. They analyzed the data statistically.

According to the investigators, in recently published European prophylactic intracameral cephalosporin studies, the incidence of postoperative endophthalmitis after unilateral cataract surgery weight-averaged to 1 in 331 (0.3%) without prophylactic intracameral antibiotics and to 1 in 1,977 (0.05%) with prophylactic intracameral antibiotics, whereas studies in the United States using only topical antibiotics reported infection rates as low as 0.028%. They reported that four cases of bilateral simultaneous endophthalmitis after ISBCS have been reported in the past 60 years, all with breaches of aseptic protocol and that no bilateral simultaneous endophthalmitis occurred in the 95,606 ISBCS cases collected. The overall rate of postoperative endophthalmitis afer ISBCS was 1 in 5,759 and infection rates were significantly reduced with intracameral antibiotics to 1 in 14,352 cases.

In conclusion, the risk for postoperative endophthalmitis in ISBCS appears to be at least as low as, and possibly lower than, published rates for unilateral surgery, particularly when recommended precautions are taken. Intracameral antibiotics significantly reduced the risk for postoperative endophthalmitis

SOURCE: Arshinoff SA, Bastianelli PA. Incidence of postoperative endophthalmitis after immediate sequential bilateral cataract surgery. J Cataract Refract Surg. 2011;37(12):2105–2114.


http://www.revophth.com/ParkCity2012






Circulation of Neural Stem/Progenitor Cells in Peripheral Blood of Patients with Neovascular AMD

Recent reports suggest that bone marrow-derived stem/progenitor cells (SPCs) play a crucial role in the development and progression of the neovascular form of age-related macular degeneration (AMD) manifested with choroidal neovascularization (CNV). Polish researchers investigated whether undifferentiated non-haematopoietic stem cells, including those capable of differentiating into neural phenotypes, play a role in the pathological state of CNV formation.

They collected peripheral blood samples from 46 patients diagnosed with CNV and from 46 controls. They also counted the CXCR4-Lin-CD45 stem cells and analyzed them by flow cytometry. Using qRT-PCR and immunocytofluorescence, the study researchers analyzed the expression of early neural and glial cell markers (β-III-tubulin, nestin and glial fibrillary acidic protein) in the sorted cells and correlated these data with plasma concentrations of stromal cell-derived factor 1 (SDF-1) (enzyme-linked immunosorbent assay), which is a pivotal chemokine that regulates the trafficking of SPCs.

The researchers found that the number of circulating CXCR4-Lin-CD45 cells did not differ in patients with active CNV as compared to the controls. However, they noticed significant intracellular overexpression of β-III-tubulin in the cells derived from AMD patients. Moreover, they observed significantly lower SDF-1 plasma levels in neovascular AMD patients compared to healthy individuals.

Their findings suggest that neural progenitor cells, together with low SDF-1 concentrations, may play a considerable role in the process of AMD progression. Further investigations aimed at the precise elucidation of these issues may help with the future development of effective prevention against, and the treatment of, this disease.

SOURCE: Machalińska A, Klos P, Safranow K, et al. Neural stem/progenitor cells circulating in peripheral blood of patients with neovascular form of AMD: a novel view on pathophysiology. Graefes Arc Clin Exp Ophthalmol. 2011;249(12):1785–1794.


http://www.revophth.com



Differences in Topography Between Large and Normal Optic Discs

A total of 69 subjects with macrodisc (disc area >2.82 mm²) and 91 healthy controls (disc area between 1.16 and 2.82 mm²) were recruited to investigate the optic nerve head parameters of healthy macrodiscs to provide standard measurements for them to be the basis for future quantitative comparisons.

Following a complete ophthalmic exam, confocal scanning laser ophthalmoscopy (SLO) was performed in all participants. The stereometric parameters of confocal SLO examination and the proportion of subjects classified as normal, borderline and glaucomatous by the Moorfield Regression Analysis were compared between groups.

Included in this study were 160 patients. It was noted that the average disc sizes in the control and macrodisc groups were 2.14±0.33 mm² and 3.36±0.36 mm², respectively. Cup area (p<0.001), rim area (p=0.01), cup volume (p<0.001), cup/disc area ratio (p<0.001), linear cup/disc ratio (p<0.001), mean cup depth (p<0.001), maximum cup depth (p<0.001) and cup shape measure (p<0.001) differed significantly between the two groups. It was reported that the parameters of the optic nerve head that did not differ significantly between groups were rim volume (p=0.17) and height variation contour (p=0.88). Furthermore, a significantly higher number of eyes were erroneously identified as abnormal (15.1% vs 79.4%) by Moorfield Regression Analysis in the macrodisc group (p<0.001).

To conclude, rim volume and height variation contour were the only optic nerve head topographic parameters that were similar in eyes with large and normal disc sizes. They seem to be promising parameters in the evaluation and comparison of the optic nerve head of subjects with macrodisc.

SOURCE: Cankaya AB, Simsek T. Topographic differences between large and normal optic discs: a confocal scanning laser ophthalmoscopy study. Eur J Ophthalmol. 2012;22(1):63–69.






  • RESULTS OF REGENERON'S PHASE 3 STUDIES OF EYLEA IN WET AMD SHOW IMPROVEMENT IN VA. Regeneron Pharmaceuticals, Inc. and Bayer HealthCare have announced that in an integrated analysis of two parallel Phase 3 studies (VIEW 1 and VIEW 2) in patients with wet age-related macular degeneration (AMD), patients treated with EYLEA (aflibercept) Injection For Intravitreal Injection showed a sustained improvement in visual acuity at 96 weeks versus baseline. During the first year of the VIEW 1 and VIEW 2 studies, patients were treated with three different dosing regimens of EYLEA, 0.5 mg every four weeks, 2 mg every four weeks and 2 mg every eight weeks (following three initial monthly injections), compared to ranibizumab 0.5mg every four weeks. In the second year of the studies, patients were treated with the same dose per injection. In an integrated analysis of the VIEW 1 and VIEW 2 studies, the visual acuity gain from baseline in the EYLEA 2mg every eight week group at week 96 was 7.6 letters, compared to 8.4 letters at week 52, with an average of 11.2 injections over two years and 4.2 injections during the second year. (The visual acuity gain from baseline in the monthly ranibizumab group at week 96 was 7.9 letters compared to 8.7 letters at week 52, with an average of 16.5 injections over two years and 4.7 injections during the second year.) Click here to learn more about the VIEW studies and for more detailed study results.
  • CE MARK APPROVAL GIVEN TO VICTUS FEMTOSECOND LASER PLATFORM. In a recent press release, Bausch + Lomb and Technolas Perfect Vision GmbH (TPV) announced the securing of CE Mark approval and commercial availability of the VICTUS Femtosecond Laser Platform in the European Union (EU). Not yet approved in the United States, the VICTUS platform is approved in the EU for LASIK flap, astigmatic keratotomy, INTRACOR, capsulotomy and lens fragmentation. As previously announced, Bausch + Lomb and TPV will promote the VICTUS platform globally, leveraging their combined cataract and refractive expertise and commercial capabilities.
  • RAYNER RECEIVES CE MARK APPROVAL FOR MULTIFOCAL TORIC IOL. Rayner Intraocular Lenses Limited has reported that it has received CE Mark approval for the Sulcoflex Multifocal IOL, completing the product family of Sulcoflex lenses and allowing the company to expand its range of IOLs offered in the European Union. Rayner expects to release the product into the market during the first quarter in 2012. Read more at www.rayner.com.
  • FDA GRANTS TEARLAB'S PETITION FOR CLIA WAIVER CATEGORIZATION OF ITS TEARLAB OSMOLARITY SYSTEM. Based on a supervisory review of TearLab Corporation's appeal, the FDA has granted its petition for a waiver under CLIA for the TearLab Osmolarity System, which uses a novel lab-on-a-chip approach that requires less than 50 nL of tear fluid to measure tear osmolarity. Upon TearLab's submission of labeling acceptable to the FDA, the CLIA waiver will be issued. Read more here.




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