Volume 9, Number 35
Monday, September 7, 2009



Due to the Labor Day holiday, there is no issue of Review of Ophthalmology Online this week. Our staff wishes you a safe and enjoyable weekend.





http://www.combigan.com/






Presence of Complement Factor P in Choroidal Neovascular Membranes of AMD Patients

Using a study population of 26 AMD patients (26 eyes) with the exclusion criterion of prior treatment of the choroidal neovascular membranes, investigators evaluated whether complement Factor P (properdin) was present in surgically removed choroidal neovascular membranes of patients with AMD and investigated whether associated pre– and postoperative clinical characteristics can be correlated. (Factor P was detected immunocytochemically on paraffin sections [7µm] by a polyclonal rabbit antihuman antibody.

The investigators found that 11 of 22 assessable membranes showed a positive reaction for Factor P and that the average percentage of Factor P-positive cells per membrane ranges from 0.65% to 4.09%. Additionally, the duration of visual loss was significantly longer (8.6 ± 2.7 vs. 3.9 ± 0.8 months) and the size of postoperative measured area of atrophic retinal pigment epithelium was larger (27.6 ± 7.6 vs. 15.0 ± 6.9 mm²) in patients with Factor P–positive membranes compared with Factor P-negative membranes.

According to the study investigators, Factor P was expressed in 50% of choroidal neovascular membranes of patients with AMD and the group with Factor P-positive membranes differed significantly from the Factor P–negative group in key clinical outcomes. They advise that additional studies investigate the role of Factor P in the development of AMD for potential therapeutic intervention.

SOURCE: Wolf–Schnurrbusch UE, Stuck AK, Hess R, et al. Complement factor P in choroidal neovascular membranes of patients with age–related macular degeneration. Retina 2009;29(7):966–973.






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Gene Expression Patterns of NVAMD in Peripheral White Blood Cells

Researchers in this study evaluated whether AMD is associated with gene expression patterns in white blood cells (WBCs) and whether such a pattern may serve as a biomarker for the disease.

They performed microarray analysis of gene expression in peripheral WBCs on neovascular AMD (NVAMD) patients (n=16) and controls (n=16) and validated the results using quantitative real time RT–PCR (QPCR) on another set of patients (n=26) and controls (n=29), respectively. The study researchers evaluated QPCR findings using receiver operator characteristics (ROC) curves and correlated with genotyping for the major risk single nucleotide polymorphisms (SNPs) for AMD in the genes for complement factor H and LOC387715.

The researchers identified NVAMD associated expression for eight sequences [false discovery rate (FDR) =0%] and 167 genes (FDR = 10%), respectively. There was an enrichment of genes involved in antigen presentation among the AMD-associated genes (p=0.0029) and QPCR confirmed increased expression (1.6 to 4.3–fold) of four genes (HSPA8, IGHG1, ANXA5, VKORC1) in association with NVAMD (p=0.02-0.0002). Furthermore, the researchers noted that the area under the curve (AUC) for these genes ranged from 0.776 to 0.815. Gene expression was not associated with genotyping for risk SNPs or WBC counts.

In conclusion, NVAMD is associated with altered gene expression in peripheral WBCs, which is not underlined by the major risk SNPs for the disease. Such altered expression may potentially serve as a biomarker for the disease, the researchers determined. These data support the involvement of systemic immune response in the pathogenesis of AMD.

SOURCE: Lederman M, Weiss A, Chowers I. Neovascular age related macular degeneration is associated with specific gene expression patterns in peripheral white blood cells. Invest Ophthalmol Vis Sci 2009; Aug 13 [Epub ahead of print].






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Comparison of OCT in Neovascular AMD to Fluorescein Angiography and Visual Acuity

This prospective study of 14 patients with choroidal neovascularization (CNV) secondary to AMD receiving photodynamic therapy (PDT) assessed the sensitivity and specificity of optical coherence tomography (OCT) for monitoring patients with CNV after PDT in comparison to fluorescein angiography (FA).

Best-corrected visual acuity (BCVA), fluorescein angiography and OCT were performed before and at 2, 6, 12 and 24 weeks after treatment and FA images were assessed for leakage and presence of subretinal or intraretinal fluid on OCT images. Moreover, retinal thickness was measured automatically and OCT sensitivity and specificity levels for detecting leaking CNV were calculated. Retinal thickness was correlated with visual acuity.

Mean follow-up time in this study was 14.1 weeks and 61 OCT/FA examinations were analyzed. It was noted that 31 examinations presented leakage (51%) and OCT showed intraretinal fluid in 46 (75%) and subretinal fluid in 30 cases (49%). Additionally, in 49 cases (80%), either intraretinal or subretinal fluid was present. Sensitivity for detecting intraretinal fluid in OCT was 90% (specificity 40%) and 71% (specificity 73%) for subretinal fluid. Combined sensitivity for intraretinal or subretinal fluid was 97% (specificity 37%) and increased central foveal thickness correlated with decreased BCVA. Correlations were significant (p<0.05).

It was concluded that OCT showed good sensitivity in detecting active CNV. Specificity was only moderate and central foveal thickness correlated negatively with visual acuity. It was suggested that, owing to different aspects of active CNV shown by FA and OCT, OCT should be combined with other examinations, and may not substitute FA for indication/reindication of PDT, but can be a valuable addition in difficult cases.

SOURCE: Henschel A, Spital G, Lommatzsch A, Pauleikhoff D. Optical coherence tomography in neovascular age related macular degeneration compared to fluorescein angiography and visual acuity. Eur J Ophthalmol 2009;19:831–835.




Using Age and Refraction to Determine Refractive Stability After Refractive Surgery

To analyze the process of emmetropization and to determine the potential for progression of refractive error following refractive surgery, the authors of this study retrospectively examined the prevalence of refractive error in 46,384 consecutive patients (77,124 eyes) at an outpatient clinic in Amman, Jordan. They also obtained biometry in 4,240 eyes and determined correlation of axial length and corneal power as a function of age based on these data.

Patients were distributed into four distinct groups: emmetropia, hyperopia, low to moderate myopia and high (>6.00D) myopia and the study authors found the prevalence of myopia to be 23.8%. Also that high myopia occurred in 3.8% of patients and that 17.5% of patients were hyperopic. They found that patients with <1.00D of myopia at age 10 and <3,00D of myopia at the time of refractive surgery had a stable refraction at age 18. Furthermore, in patients with high myopia, 7.4% demonstrated a progression of corneal power and axial length that does not stabilize until age 30 and finally, the refractive error of hyperopic patients tended to progress from age 30 to age 50.

Myopes with <1.00D of myopia at age 10 and <3.00D of myopia at the time of refractive surgery are unlikely to progress, the authors concluded. They also noted that high myopes and hyperopes have potential to progress and that patients in which the axial length of the eye exceeds 26 mm in conjunction with higher corneal powers are likely in a state of decomposition and are at risk of marked progression of refractive error following refractive surgery. Additionally, they suggested that the likelihood of progression be determined prior to surgery as well as explained to the patient.

SOURCE: Sayegh FN. Age and refraction in 46,000 patients as a potential predictor of refractive stability after refractive surgery. J Refract Surg 2009;25:747–751.









  • PROMISING DATA FROM PHASE 2 STUDY OF EYE DROP FOR DRY EYE. A Phase 2 clinical study evaluating Resolvyx Pharmaceuticals, Inc.'s RX–10045, a resolvin administered as a topical eye drop for the treatment of patients with chronic dry eye syndrome, has produced positive data. The trial examined three doses of RX–10045 and utilized a controlled adverse environment (CAE) to measure corneal staining in a stressful drying environment, as well as daily patient diaries using a standard visual analog scale to assess symptom improvement over he course of the study. According to Resolvyx, in the 28–day, randomized, multi-center, placebo–controlled, 232-patient trial, RX–10045 produced dose-dependent, statistically significant improvement on the primary endpoints for both the signs and symptoms of dry eye and was generally shown to be safe and well tolerated. These Phase 2 results represent the first demonstration of clinical efficacy for the novel class of resolving compounds and suggest that resolvins have the potential to treat a broad range of inflammatory diseases, commented the company. Additional information can be found here.
  • SUBJECT ENROLLMENT FOR RETINITIS PIGMENTOSA DRUG COMPLETE R-Tech Ueno, Ltd. has announced the completion of subject enrollment in its Phase 2 clinical study of 0.15% UF–021 (generic name, isopropyl unoprostone; active ingredient of Rescula Eye Drops) in patients with retinitis pigmentosa. The company submitted the notification of the clinical trial in August 2008 and enrollment in the phase 2 study began at six clinical sties in late December 2008 and was completed on August 3, 2009. According to R-Tech Ueno, the clinical study has progressed with no delay, no serious adverse effects and only a few cases of discontinuation so far. The study is expected to be completed by next spring, including data collection and analysis. Learn more here.
  • PRELIMINARY PHASE 3 RESULTS FOR XIBROM POSITIVE, SAYS ISTA. According to ISTA Pharmaceuticals, Inc., the preliminary Phase 3 results from its Xibrom (bromfenac ophthalmic solution) 0.09% QD (once daily) confirmatory study are positive. Xibrom 0.09% QD achieved statistical significance in the study's primary endpoint (the absence of ocular inflammation 15 days following cataract surgery), says ISTA, and the secondary efficacy endpoint (the elimination of ocular pain one day post surgery). A company press release stated that during the study, no serious ocular or systemic adverse events occurred, and the safety profile is consistent with ISTA's currently marketed Xibrom twice-daily formulation.
  • ALIMERA CLOSES EXTENSION OF SERIES C FINANCING. Alimera Sciences, Inc., has closed a $55million extension of its Series C financing, which was originally completed in March 2008. The purchasers of the $5million in Series C preferred stock received warrants for an additional $510million in Series C preferred stock and the warrant holders will have up to 30 days from the delivery of Phase III top–line data for Iluvien (an investigative, extended–release intravitreal insert that Alimera is developing for the treatment of diabetic macular edema) to elect to exercise the warrants. According to Alimera, if the majority of the holders of warrants make such election, then all warrant holders will be required to exercise their warrants in full. The company expects to receive the Phase III top–line data for Iluvien in December 2009.

 




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