Volume 4, Number 7

Monday, February 16, 2004

In this issue: (click heading to view article)
		Bone Marrow-derived Progenitor Cells May Contribute to CNV
		New Instrument for Fluid Drainage or Injection in Within Subretinal Space
		Gene Expression in Keratoconus
		Effect of Hormone Therapy on Risk for ARM in Postmenopausal Women
		A logMAR Alternative to the Snellen Chart
		Briefly

Bone Marrow-derived Progenitor Cells May Contribute to CNV Bone marrow-derived progenitor cells are a source of endothelial and smooth muscle-like cells in choroidal neovascularization (CNV), according to a study by the Bascom Palmer Eye Institute, Miami. The pathogenesis of CNV is postulated to be driven by angiogenesis, a process in which the cellular components of the new vessel complex are derived from cells resident within an adjacent preexisting capillary. Recently, an alternative paradigm, termed postnatal vasculogenesis, has been shown to contribute to some forms of neovascularization. In vasculogenesis, the cellular components of the new vessel complex are derived from circulating vascular progenitors from bone marrow. In the current study, transplantation of green fluorescent protein (GFP)-labeled bone marrow and laser-induced CNV were combined to examine the contribution of vasculogenesis to the formation of CNV. Ten adult C57BL/6 female mice were used as recipients for bone marrow transplantation. Bone marrow was obtained from three C57BL/6 female mice transgenic for the beta-actin promoter GFP. One month after bone marrow transplantation, CNV was induced in recipient mice by making four separate burns in the choroid of each eye with a red diode laser. Four weeks after CNV was induced, eyes of recipient mice were processed for immunohistochemistry to detect GFP and markers for vascular smooth muscle cells (alpha-smooth muscle actin, desmin and NG2 chondroitin sulfate proteoglycan), endothelial cells (CD31, BS-1 lectin) or macrophages (F4/80). GFP-labeled cells represented 17 percent of the total cell population in the lesion. Many of the GFP-labeled cells were immunoreactive for alpha-smooth muscle actin (39 percent), desmin, NG2, CD31 (41 percent), BS-1 lectin, or F4/80. GFP-labeled cells were morphologically indistinguishable from cells normally present in CNV lesions.

Espinosa-Heidmann DG, Caicedo A, Hernandez EP, et al. Bone marrow-derived progenitor cells contribute to experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 2003;44(11):4914-9.

New Instrument for Fluid Drainage or Injection in Within Subretinal Space A newly developed instrument, the subretinal aspiration and injection device (SR-AID) may provide an efficient and safe means of access to the subretinal space for controlled external drainage or injection of fluid, according to researchers at the Sungkyunkwan University School of Medicine in Seoul, Korea. The SR-AID is formed by an assembly of a probe, handle body and a driving unit. The curved conduit within the probe segment forms a curved tunnel and acts as a guide along which a needle moves back and forth. The feasibility of fluid injection beneath the attached retina was tested in animal eyes. The efficacy of subretinal fluid drainage with the SR-AID was assessed in six cases of clinical retinal detachment. External approach to the subretinal space under ophthalmoscopic monitoring can be achieved by oblique angle penetration of the scleral wall with a needle from the SR-AID. Fluid was injected successfully into the subretinal space in three of six rabbit eyes and in two of two pig eyes. The mean duration required for the drainage of subretinal fluid with the SR-AID was 127 seconds. There was no incidence of significant subretinal hemorrhage or retinal perforation in the animal experiments and in human cases.

SOURCES: Kang SW, Kwon HN, Lee HW, et al. A new instrument for drainage or injection of fluid within subretinal space. Retina 2003;23(5):661-6.

Gene Expression in Keratoconus Despite intensive investigations, the exact cause of keratoconus still remains unclear. Clinical studies provide strong indications of a major genetic role in the etiology of the disease. In this study, German researchers examined the involvement in the manifestation of keratoconus of any of the 5,600 gene specificities available on the Affymetrix GeneChip HuGeneFL. After they examined two corneas, researchers stored them in RNAlater, and RNA was extracted and hybridized on the chips. Using a combination of dyes, they were able to read the chips with laser detection and visualize the gene expression pattern. Results showed an up-regulation of collagens, versican, metalloproteinases and cell adhesion proteins. A down-regulation was observed for TIGR protein, cytokeratins, eyes absent homologue and the proteins for radical treatment selenoprotein P and monooxygenase. Results suggest that keratoconus is a process in which repair and scar-formation mechanisms operate at the same time and that as candidate genes for this mechanism, collagen IV and related proteoglycans are favored.

SOURCE: Bochert A, Berlau J, Koczan D, et al. Gene expression in keratoconus: initial results using DNA microarrays [article in German]. Der Ophthalmologe 2003;100(7):545-9.

Effect of Hormone Therapy on Risk for ARM in Postmenopausal Women Postmenopausal hormone therapy (HT) may not affect the risk for either early or late age-related maculopathy (ARM) in women aged 60 to 80 years; additionally, a history of ischemic heart disease may be associated with an increased risk for ARM, according to a study by Hadassah Medical Center in Jerusalem. In a cross-sectional, controlled study, 102 women 60 to 80 years old who were receiving HT and 100 controls underwent a detailed clinical funduscopic evaluation and stereoscopic fundus photography for the presence and grading of ARM. All participants completed a standardized questionnaire regarding vascular risk factors, HT and lifetime exogenous and endogenous estrogen and progesterone exposure. Statistical analysis was performed using Student"s t test, Chi2 test, and a multivariate logistic regression model. The HT and the non-HT groups did not differ in terms of early (11 percent vs. 15 percent), late (6 percent vs. 6 percent), or wet (2 percent vs. 2 percent) ARM prevalence rates. Women with ARM were significantly older than controls (69 vs. 66 years) and were more likely to have ischemic heart disease (21 percent vs. 9 percent). Lifetime exogenous and endogenous hormone exposures and other cardiovascular risk factors were not significantly different among women with ARM as compared with controls.

SOURCE: Abramov Y, Borik S, Yahalom C, et al. The effect of hormone therapy on the risk for age-related maculopathy in postmenopausal women. Menopause 2004;11(1):62-8.

A logMAR Alternative to the Snellen Chart The compact reduced logMAR (cRLM) chart is being developed as a logMAR alternative to the Snellen chart. It is more closely spaced and has fewer letters per line than conventional logMAR charts. Information regarding the performance of such a chart in amblyopes and children is therefore required. This study, conducted by British researchers, aimed to investigate the performance of the cRLM chart in amblyopic children. Timed test and retest measurements using two versions of each chart design were obtained on the amblyopic eye of 43 children. Using the methods of Bland and Altman the agreement, test-retest variability (TRV) and test time of the cRLM and the current clinical standard Snellen chart were compared to the gold standard ETDRS logMAR chart. Results showed no systematic bias between chart designs. For line assignment scoring, the respective TRVs were 0.20 logMAR, 0.20 logMAR, and 0.30 logMAR. Single-letter scoring TRVs were cRLM logMAR, ETDRS logMAR and Snellen logMAR. Median testing times were ETDRS 60 seconds, cRLM 40 seconds, Snellen 30 seconds. The sensitivity to change of the cRLM equaled or approached that of the gold standard ETDRS and was at least 50 percent better than that of Snellen. This enhanced sensitivity to change was at the cost of only a 10-second time penalty compared to Snellen. The cRLM chart was approximately half the width of the ETDRS chart. The cRLM chart may represent a clinically acceptable compromise between the desire to obtain logMAR acuities of reasonable and known sensitivity to change, chart size, and testing time.

SOURCE: Laidlaw DAH, Abbott A, Rosser DA. Development of a clinically feasible logMAR alternative to the Snellen chart: performance of the "compact reduced logMAR" visual acuity chart in amblyopic children. Br J Ophthalmol 2003;87:1232-4.

BRIEFLY FDA PANEL RECOMMENDS APPROVAL OF REFRACTEC CK SYSTEM. Refractec recently announced that the FDA Ophthalmic Devices Panel voted unanimously to recommend approval of the Viewpoint CK System, used to perform the Conductive Keratoplasty (CK) procedure for the improvement of near vision in emmetropic presbyopes and hyperopic presbyopes. The CK system is the first to be reviewed by the FDA specifically for presbyopic patients who want to improve their near vision. The FDA approved the CK system in 2002 for patients older than 40 with hyperopia. The panel’s new recommendation was based on clinical 12-month follow-up data in which CK demonstrated effectiveness in significantly improving a patient’s near vision: 94 percent of patients could see J5 (magazine- and newspaper-size print) in the eye that was treated; 83 percent of patients could see 20/20 and read J3 or phonebook-size print. No serious, sight-threatening or unanticipated safety events were reported. LUMIGAN APPROVED IN EUROPE AS FIRST-LINE GLAUCOMA, OCULAR HYPERTENSION THERAPY. The European Commission has approved Allergan"s Lumigan (bimatoprost ophthalmic solution, 0.03%) as first-line therapy for the reduction of elevated intraocular pressure in chronic open-angle glaucoma and ocular hypertension. Lumigan was approved by the FDA in 2001 and by the European Commission in 2002 but was indicated only for patients who were insufficiently responsive, intolerant or contraindicated to first-line therapy. Under the new indication, European ophthalmologists can initiate Lumigan therapy immediately. CIBA VISION FINALIZES SALE OF SURGICAL BUSINESS. CIBA Vision has completed the sale of a significant portion of its surgical business, which includes the following agreements: IOLTech has purchased Vivarte and Vivarte Presbyopic phakic refractive lens, CV232 SRE intraocular lens, Tear Saver and Tear Saver Plus punctum plugs, UniVisc viscoelastic, VisThesia and Ophthalin and Ophthalin Plus viscoelastics. IOLTech has also purchased certain marketing and distribution rights to the PRL phakic refractive lens. Optonol Ltd. and CIBA Vision have agreed on a mutual release of contract for the Ex-Press Mini Glaucoma Shunt; Optonol will assume distribution of the Ex-Press shunt in the United States and Canada. CIBA Vision will retain its equity share in Refocus Group; however, Refocus will reassume the licensing and all marketing rights worldwide to its PresView Scleral Implant and the Surgical Spacing Procedure for the treatment of presbyopia, glaucoma and ocular hypertension. Negotiations for the remaining products within CIBA Vision’s surgical portfolio are ongoing. CIBA Vision will provide transitional services on a case-by-case basis to new owners to minimize the effects of sale on customers and their patients.

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