Volume 5, Number 5
Monday, February 7, 2005



In this issue: (click heading to view article)
Editorial: Protecting Patients’ Rights
Identification of a Novel Adult-onset POAG Gene
Reversal of Disc Cupping After IOP Reduction in Topographic Image Series
Mass Treatment with Single-dose Azithromycin for Trachoma
Transplantation of Autologous RPE in AMD
Briefly











Editorial: Protecting Patients’ Rights

The recent elections in Iraq highlighted how very special certain rights that we have truly are. Unfortunately, all too often we take those rights for granted, and their value goes unappreciated or unprotected.

Patients have rights as well--and we must respect them. This may come to something as simple as maintaining an honest and open relationship with them as their physician, respecting their right to maintaining privacy about health-related matters, or remaining current via continuing medical education. Arguably, an additional right of patients is the right to expect that, as their physicians, we will not put profit before their healthcare. A case in point: the recent discovery that a Fort Lauderdale clinic administered an unapproved Botox knockoff to several patients, inducing symptoms and signs of botulism. Although I am not a party to all the details concerning this incident, the general perception that this was done for profit and for no other reason seems plausible to me. And that makes it wrong.

The citizens of Iraq relish their new freedom to vote, and they outwardly expressed their pleasure in doing so. Let us not lose sight of the many rights that we have, and let us be sure to take a moment every day to stop and consider them and be thankful for them. And let us not, as physicians, forget the rights of our patients. Some day, the shoe will be on the other foot, and those patients’ rights will become quite important to us.
Stephen E. Pascucci, MD
Medical Editor
[email protected]

Table of Contents











Identification of a Novel Adult-onset POAG Gene

Glaucoma is a leading cause of blindness in virtually every country. Development of an accurate diagnostic test for presymptomatic detection of at risk individuals is an urgent requisition for this condition. Researchers in the United States, England, and Canada have mapped a new adult-onset primary open-angle glaucoma (POAG) locus on 5q22.1 (GLC1G) and have identified its defective gene.

Mutation screening of seven candidate genes from the GLC1G critical region identified only one significant alteration in the WDR36 (WD40-Repeat 36) gene. This mutation segregated in all affected members of our first GLC1G-linked family, but it was absent in 476 normal control chromosomes. Further screening of the gene in a total of 130 POAG families revealed 24 DNA variations. Overall, four mutations were identified in 17 unrelated POAG subjects (5.02 percent to 6.92 percent), 11 with high-pressure and six with low-pressure glaucoma. These mutations were absent in a minimum of 200 normal control chromosomes; furthermore, they were conserved between WDR36 orthologues in mouse, rat, dog, chimp and human.

WDR36 is a novel gene with 23 exons that encodes for 951-amino acids and a protein with multiple G-beta WD40 repeats. Using Northern blotting, scientists observed two distinct mRNA transcripts in human heart, placenta, liver, skeletal muscle, kidney and pancreas. WDR36 gene expression in lens, iris, sclera, ciliary muscles, ciliary body, trabecular meshwork, retina and optic nerve were established by Reverse Transcription Polymerase Chain Reaction (RT-PCR). In mouse, two transcripts of 3.5-kb and 2.9-kb showed analogous expression patterns to those of humans. mRNA expressions were detected in seven-, 11-, 15- and 17-day-old developing mouse embryos. The authors believe that WDR36 is a novel causative gene for adult-onset POAG. Specific ocular expressions and observed mutations are consistent with the role of this gene in the etiology of both high- and low-pressure glaucoma.

SOURCE: Monemi S, Spaeth G, DaSilva A, et al. Identification of a novel adult-onset primary open angle glaucoma (POAG) gene on 5q22.1. Hum Mol Genet 2005;Jan 27 [Epub ahead of print].		 Table of Contents











Reversal of Disc Cupping After IOP Reduction in Topographic Image Series

Researchers at Moorfields Eye Hospital in London, conducted a study aimed at identifying and characterizing "reversal" of optic nerve cupping following intraocular pressure (IOP) lowering in scanning laser tomography (SLT) longitudinal image series.

In the study, the investigators modified a previously described analytical approach toward longitudinally studying putatively increased rim area following IOP lowering. Sustained IOP reduction of 25 percent was by topical medication. Forty SLT image series with equivalent follow up were assessed: 10 with ocular hypertension (OHT), 10 with primary open angle glaucoma (POAG) and 20 normal as controls. Reproducible rim area reversal was identified by sector and its time-course over one year examined.

By a two-of-three reproducibility criterion, reversal following IOP lowering was confirmed in about one-third of treated eyes (POAG and OHT), but not in any controls. Rim sectors showing reversal were mostly nasal, with a few occurring superotemporally. Reversal in one-fifth of treated eyes persisted for at least one year; all these were in the nasal half of the disc. The number of sectors with persisting reversal affected less than six percent of all treated eyes" rim sectors.

The results suggest that rim area is not uncommonly increased after IOP lowering and this "reversal" may persist for at least a year. Within topically treated eyes having IOP lowering of at least 25 percent, the proportion of rim sectors with persistent reversal appears small. Nevertheless, the authors stress that the effects of IOP reduction on topography, especially in the short term, should be considered when longitudinally assessing progressive rim loss in SLT images.

SOURCE: Tan JC, Hitchings RA. Reversal of disc cupping after intraocular pressure reduction in topographic image series. J Glaucoma 2004;13(5):351-5. 		Table of Contents






Mass Treatment with Single-dose Azithromycin for Trachoma

Trachoma, caused by repeated ocular infection with Chlamydia trachomatis, is an important cause of blindness. Current recommended dosing intervals for mass azithromycin treatment for trachoma are based on a mathematical model. Investigators at the London School of Hygiene and Tropical Medicine collected conjunctival swabs for quantitative polymerase-chain-reaction (PCR) assay of C. trachomatis before and two, six, 12, 18 and 24 months after mass treatment with azithromycin in a Tanzanian community in which trachoma was endemic. For ethical reasons, at six, 12 and 18 months, they administered tetracycline eye ointment to residents who had clinically active trachoma.

At baseline, 956 of 978 residents (97.8 percent) received either one oral dose of azithromycin or (if azithromycin was contraindicated) a course of tetracycline eye ointment. The prevalence of infection fell from 9.5 percent before mass treatment to 2.1 percent at two months and 0.1 percent at 24 months. The quantitative burden of ocular C. trachomatis infection in the community was 13.9 percent of the pre-treatment level at two months and 0.8 percent at 24 months. At each time point after baseline, more than 90 percent of the total community burden of C. trachomatis infection was found among subjects who had been positive the previous time they were tested.

The prevalence and intensity of infection fell dramatically and remained low for two years after treatment. The authors of the study believe that one round of very high-coverage mass treatment with azithromycin, perhaps aided by subsequent periodic use of tetracycline eye ointment for persons with active disease, can interrupt the transmission of ocular C. trachomatis infection.

SOURCE: Solomon AW, Holland MJ, Alexander ND, et al. Mass treatment with single-dose azithromycin for trachoma. N Engl J Med 2004;351(19):1962-71. 		Table of Contents






Transplantation of Autologous RPE in AMD

Results of a study by Austrian and German researchers suggest that autologous transplantation of retinal pigment epithelium (RPE) is a beneficial supplement to membrane excision alone in patients with foveal choroidal neovascularization (fCNV) in age-related macular degeneration (AMD).

Fifty-three eyes of patients with fCNV who were not eligible for laser or photodynamic therapy were included in the study. They underwent subretinal membrane excision with simultaneous transplantation of autologous RPE cells. Eyes with membrane excision alone served as the control. Tests included best corrected visual acuity for far and near with Early Treatment Diabetic Retinopathy Study (ETDRS) and Jaeger charts, multifocal (mf)ERG, central visual field analysis, optical coherence tomography (OCT) and angiography, before surgery and one month and three months after treatment, and at three-month intervals thereafter.

In 39 eyes, RPE transplantation was performed (Group 1); 14 eyes had membrane excision alone (Group 2). In Group 1, visual acuity improved significantly, by two or more lines in 21 (53.8 percent) patients; remained stable in 12 patients (30.8 percent); and decreased two or more lines in six patients (15.4 percent). In Group 2, the corresponding values were 21.1 percent, 57.8 percent, and 21.1 percent. Statistical analysis of results in the two groups showed a trend in favor of Group 1. The difference in reading acuity was significant between the two groups (mean change in Group 1: 1.85 +/- 0.42 vs. 0.43 +/- 0.47 in Group 2). mfERG response density changes were significantly different between Groups 1 and 2. No significant decreases in central visual field defects were detected. OCT showed the postoperative median retinal thickness in the lesion area in Group 1 was higher (242.31 +/- 12.30 µm) than in Group 2 (202.07 +/- 10.68 µm), showing a trend. The authors believe these results suggest that this method may be regarded as a reasonable treatment option for AMD.

SOURCE: Binder S, Krebs I, Hilgers RD, et al. Outcome of transplantation of autologous retinal pigment epithelium in age-related macular degeneration: a prospective trial. Invest Ophthalmol Vis Sci 2004;45(11):4151-60. 		Table of Contents





BRIEFLY
  • GENAERA REPORTS POSITIVE PRELIMINARY DATA FROM AMD STUDY. Genaera Corporation has announced positive preliminary clinical results, including improved vision, from a multicenter open-label U.S. Phase II clinical trial (MSI-1256F-207) with squalamine for the treatment of choroidal neovascularization associated with AMD. Preliminary results from six patients treated with 40 mg of squalamine, each of whom suffered from wet AMD in both eyes, demonstrated that of 100 percent of 12 eyes had preserved or improved vision at Week 3 (after two doses of squalamine), Week 5 (end of therapy) and two months after initiation of therapy. The greatest degree of improvement at two months was a gain relative to baseline of 28 letters (5.6 lines), while the greatest degree of loss was 11 letters on the ETDRS chart. In clinical trials of therapies for wet AMD, gain or loss of less than 15 letters (three lines) on the ETDRS chart constitutes stable vision, while gain equal to or greater than 15 letters constitutes improved vision. All patients received four weekly doses of squalamine, with no further maintenance therapy. No withdrawals from therapy or drug-related serious adverse events have occurred thus far in the trial. Genaera is currently conducting three Phase II trials of squalamine in AMD at multiple sites throughout the United States. Recently, the FDA selected squalamine for participation in the Continuous Marketing Application (CMA) Pilot 2 program. In October 2004, the FDA granted squalamine Fast Track designation. For more information, go to www.genaera.com, or call Genaera"s Clinical Trial Hotline, 800-299-9156.
  • MIRAVANT TO CONDUCT PHOTREX CONFIRMATORY STUDY FOR AMD. Miravant Medical Technologies will conduct a Phase III confirmatory clinical trial of Photrex (rostaporfin, formerly known as SnET2) for wet age-related macular degeneration (AMD), based on a Special Protocol Assessment by the FDA. The FDA requested this single confirmatory study in its Approvable Letter issued September 2004, after reviewing the Miravant’s New Drug Application (NDA) for SnET2. The placebo-controlled trial, to be conducted outside of the United States, is designed to enroll a broad range of wet AMD patients, including those with predominantly classic, minimally classic and occult lesions. Study protocol requires that each patient receive Photrex or placebo treatments over the course of nine months. Miravant plans to conduct a primary efficacy endpoint analysis at 12 months after initial treatment, which, pending positive results, will be submitted for FDA review and subsequent marketing approval. Patients will continue to be evaluated for a second year to confirm the longer-term results established in previous Photrex Phase III studies. The company expects to begin enrolling patients in mid-2005.
  • HAAG-STREIT INTRODUCES NEW SLIT LAMPS. Haag-Streit has introduced three new slit lamps: the BD, the BP-900 and the BX 900. The BD slit lamp is optimized for eyecare professionals specializing in the anterior segment. A built-in video port accepts commercially available C-mount cameras, allowing high-resolution digital and video imaging. A flip of a lever just beneath the microscope allows the practitioner to select standard magnifications of 10x and 16x. The slit can be adjusted from 0-14 mm; filters include grey, redfree, blue and yellow. The BP 900 was designed for the routine practice and features a redesigned optical system with two optional beam splitters for video and digital photography. Each beam splitter attachment accepts selected commercial digital cameras or all commercial C-mount cameras. The new Ecolite for background illumination was developed especially for imaging with the BP slit lamp. A push button on top of the joystick controls illumination levels. Tungsten is standard and the bulb gives up to 600,000 Lux illumination. Switch between 10, 16 and 25x magnifications using a dial on the side of the microscope. The BX 900 provides features for the professional ophthalmic photographer, including integrated synchronized flash, slit and background illumination and adaptors for 35mm and digital cameras. The shutter release is mounted close to the operator’s hand so it can be used while maintaining focus through the joystick of the slit lamp. During a normal examination, 100 percent of the light is directed to the oculars but for photography, a built-in retracting mirror directs 100 percent of the light to the camera. The camera is mounted above the microscope allowing easy access to the patient. Magnifications of 6.3, 10, 16, 25 or 40x are standard. Gray, redfree, blue and heat absorption filters are included. For more information on these products, call 800-787-5426 or go to www.haag-streit-usa.com.
  • PHARMOS RECEIVES MILESTONE PAYMENT FROM B&L FOR ZYLET COMMERCIAL LAUNCH. Pharmos Corp. recently received a gross milestone payment of $12.1 million from Bausch & Lomb, its former marketing partner for ophthalmology products. The payment was triggered by Bausch & Lomb"s commercial launch of Zylet, a combination anti-inflammatory and antibiotic (0.5% loteprednol etabonate and 0.3% tobramycin) to treat steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where superficial bacterial ocular infection or a risk of infection exists. The treatment was approved for marketing by the FDA on December 15, 2004. Zylet is part of the loteprednol etabonate business that Pharmos sold to Bausch & Lomb in 2001. Pharmos could earn an additional milestone payment based on Bausch & Lomb sales of Zylet over the next two years. The maximum future payment is $10 million.

Table of Contents



Check Yearly. See Clearly. Open Your Eyes To the Opportunities.
It"s only been up and running a few short weeks. Yet, it"s already clear that the Check Yearly. See Clearly.(SM) marketing campaign is opening consumers" eyes to the benefits of regular eye exams. Call the Vision Council of America at 800-424-8422 today or visit checkyearly.com for your free promotional materials.





Subscriptions: Review of Ophthalmology Online is provided free of charge as a service of Jobson Publishing, LLC. If you enjoy reading Review of Ophthalmology Online, please tell a friend or colleague about it. Forward this newsletter or send this address: [email protected]. To change your subscription, reply to this message and give us your old address and your new address; type "Change of Address" in the subject line. If you do not want to receive Review of Ophthalmology Online, reply to this message and type "Unsubscribe: Review of Ophthalmology Online" in the subject line.

Advertising: For information on advertising in this e-mail newsletter or other creative advertising opportunities with Review of Ophthalmology, please contact publisher Rick Bay, or sales managers James Henne, Michele Barrett or Kimberly McCarthy.

News: To submit news, send an e-mail, or FAX your news to 610.492.1049