Subspecialty News

RPE Cells Can Be Mass-produced; CATT Study Infections Are Analyzed; Optomap Identifies MoreRetinal Lesions


RPE Cells Can Be Mass-produced

Breakthrough could aid AMD research.

■ Scientists at the Wilmer Eye Institute reported they have developed a new, simpler way to produce human pluripotent stem cells in quantities large enough to help develop treatments for AMD. Findings from the new study are published in the April 2013 issue of Stem Cells Translational Medicine.1

“Significant interest exists in developing RPE culture systems, both to study AMD disease mechanisms and to provide substrate for possible cell-based therapies. Because of their indefinite self-renewal, human pluripotent stem cells (hPSCs) have the potential to provide an unlimited supply of RPE-like cells,” noted Donald Zack, MD, PhD, who with Julien Maruotti, PhD, led the team of Wilmer researchers along with researchers from the Institute of Vision in Paris in conducting the study.

“Most of the currently accepted methods in use for deriving RPE cells from hPSC involve time-and-labor-consuming steps done by hand, and they don’t yield large enough amount of the differentiated cells — which has posed a problem when trying to use them to develop potential new therapies,” Dr. Maruotti added.

The Zack/Maruotti team simplified RPE cell production by modifying a standard protocol for isolating the cells from spontaneously differentiating hPSC monolayers. In the new method, hPSCs were amplified by clonal propagation and the RPE cells enriched by serial passage rather than mechanical picking.

“These modifications eliminate the need for the time- and labor-consuming manual steps usually required to culture hPSCs and to purify the RPE population, and thereby provide a readily scalable approach to generate large numbers of high quality RPE cells — up to 36 times more than the best protocols previously reported during the same time interval,” Dr. Zack said.

“This improved process represents a step toward mass production of RPE and could prove useful for applications requiring large number of cells such as cell therapy, drug screening or disease modeling,” said Anthony Atala, MD, editor of Stem Cells Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

Stem Cells Translational Medicine also notes in a study published in the April 2013 issue that a team of researchers from the University of California Santa Barbara (UCSB) reported early success in speeding up RPE cell production using a multi-factorial approach.2 The UCSB team says it has had success in directing pluripotent cells to RPE in only 14 days, rather than the months this process has taken in the past. The UCSB team is headed by Dennis Clegg, PhD, Peter Coffey, PhD, and David Bucholz, PhD.


1. Maruotti J, Wahlin K, Gorrell D, Bhutto I, Lutty G, Zack DJ. A simple and scalable process for the differentiation of retinal pigment epithelium from human pluripotent stem cells. Stem Cells Trans Med. 2013 Apr 12. [Epub ahead of print]

2. Buchholz DE, Pennington BO, Croze RH, Hinman CR, Coffey PJ, Clegg DO. Rapid and efficient directed differentiation of human pluripotent stem cells into retinal pigmented epithelium. Stem Cells Trans Med . 2013; APR 18. [Epub ahead of print.]-0163


■ The following corrections and clarifications are in order for the article, “Guidelines for Preventing Blindness for Retinopathy of Prematurity” by Jonathan Sears, MD (April 2013: 54-57):

• The editors selected the figure on page 54 as an example of zone 1 disease. It is, in fact, a photograph of a threshold zone 1 eye treated with bevacizumab (Avastin, Genentech) that regressed to become fully vascularized with evidence of possible anastomotic peripheral vessels. The author did not supply the figure.

• The pull-quote on page 55 may have suggested, if taken out of context, the author was critical of the Early Treatment for Retinopathy of Prematurity (ETROP) trial. The author, in fact, informs the editors this is not the case.

• The citation of the talk at the American Ophthalmic Society on page 55 should have been attributed to John Flynn, MD, not Harry W. Flynn, Jr., MD. (Trans Am Ophthalmol Soc. 2004;102:233-248)

• The author notes that ablative treatments should be complete and that skipped areas can be avoided by double-checking the treatment has been completed at the initial laser therapy. However, on page 57, the text reads: “It is also important to note that many people describe giving a child a ‘follow-up, with additional laser treatment.’” The author hopes all children get a “follow-up” after laser, but not necessarily a “follow-up … additional laser treatment.”

Retinal Physician regrets the errors and extends apologies to Drs. Sears, John Flynn and Harry Flynn.

CATT Study Infections Are Analyzed

Antibiotics did not prevent endophthalmitis.

■ A team of researchers led by Colin A. McCannel, MD, of the Kittner Eye Center of the University of North Carolina, conducted a large-scale study to identify incident cases of endophthalmitis that occurred during the NIH-sponsored CATT trial and ascertain whether perioperative topical antimicrobials had a protective effect after intraocular injections of anti-VEGF agents. They also studied the impact of endophthalmitis on the visual acuity (VA) of patients who acquired the infection.

Through two years, patients enrolled in CATT (n=1185) were evaluated every 28 days and treated with intravitreal injection of ranibizumab or bevacizumab according to the assigned dosing regimen (monthly or PRN).

Study ophthalmologists examined patients who reported symptoms of infection and initiated treatment immediately upon diagnosis of endophthalmitis. Change in VA from the time of the last treatment injection preceding the onset of endophthalmitis symptoms to the last study visit was calculated for eyes that developed endophthalmitis.

For all patients in the CATT study, the administration and timing of topical prophylactic antimicrobials was at the discretion of the study ophthalmologist. Injections were classified into four groups based on use and timing of topical ocular antimicrobial administration: 1) pre-injection only (n=1301); 2) post-injection only (n=5247): 3) both pre and post injection (n=9961); 4) no antibiotic (n=2000). Comparisons were made for rates of endophthalmitis between all four groups.

The researchers found that 11 cases of post-injection endophthalmitis occurred among 18,509 total anti-VEGF injections. Of the 10 eyes with follow-up visual acuity, five eyes returned to VA within 10 letters (range +8 to −9) of their VA prior to injection, and five eyes lost 15 or more letters (range −17 to −63). Event rates for the four antimicrobial treatment groups were: 1) pre injection-only: 1 case (0.08%); 2) post injection-only: 3 cases (0.06%); both pre and post injection: 4 cases (0.04%); and 4) no antibiotic: 3 cases (0.15%). Differences in the incidence of endophthalmitis among the groups were not deemed statistically significant.

The researchers, who presented their findings at the recent ARVO meeting, found that endophthalmitis rates in CATT were low and consistent with the results of other large clinical trials of intraocular injections of anti-VEGF agents and triamcinolone. Infections occurred despite topical ocular antimicrobial administration, and risk did not depend on whether or not antimicrobials were used, or on the timing of antimicrobial dosing.


McCannel CA, Meredith T, Peskin E, et al. Incidence of endophthalmitis after anti-VEGF injections and use of anti-microbials in the Comparison of AMD Treatment Trials (CATT). Invest Ophthalmol Vis Sci. 2013;54:ARVO E-Abstract C009. 1114 - C0091.


Another Avastin recall. Clinical Specialties, a compounding pharmacy in Martinez, GA, has recalled 40 lots of Avastin after ophthalmologists using the drug to treat patients with wet AMD reported five cases of infection.

In addition, Balanced Solutions, a Florida compounding pharmacy, has recalled all lots of its unexpired ophthalmic products because of quality control and sterility issues.

An FDA inspection of the company’s facility found what the FDA termed “poor practices and conditions.”

Endogenous endophthalmitis and IV drug use. Researchers at the New Jersey Medical School led by Shriji Patel, MD, conducted an eight-year retrospective study of IV drug users presenting with endogenous endophthalmitis (EE).

During the period under study, 18 cases of EE associated with IV drug abuse were treated. Most patients presented with counting fingers vision or worse. Ten patients were treated with antifungals and all patients received IV antibiotics, most commonly vancomycin or ceftazidime. Sixteen eyes underwent a vitreous biopsy, seven had pars plana vitrectomy and two had anterior chamber tap.

Final BCVA at last follow-up ranged from 20/20 to NLP, with most patients having final vision of 20/400 or worse. Only four eyes (19%) had vision better than 20/400.

The researchers reviewed 21 eyes of 18 patients with EE and concurrent IVDA over an eight-year period; 10 patients with fungal EE.

The study, presented at the recent ARVO meeting, shows an extremely poor visual prognosis associated with EE in this setting.

Iluvien now available in the UK. Alimera Sciences said its sustained-release implant Iluvien for the treatment of DME is available in the UK for private pay and privately insured patients. The company has also applied for a PAS (Patient Access Scheme) that would permit government-funded reimbursement under certain guidelines.

Iridex to distribute Peregrine surgical instruments. Iridex Corporation has entered into a global distribution and supply agreement with Peregrine Surgical, Ltd. Under the agreement, Iridex will become a worldwide distributor for Peregrine-labeled instruments for vitreoretinal surgery and Peregrine Surgical will become part of the Iridex supply chain for the manufacture of certain Iridex products.

ACT moves patients to higher stem cell dosages. Advanced Cell Technology, Inc., a pioneer in using stem cells as a potential therapy for retinal disease, said it had begun treating a third cohort of patients with higher dosages of stem cells in each of its two US clinical trials for forms of macular degeneration.

The patients were injected with 150,000 human embryonic stem cell-(hESC)-derived retinal pigment epithelial (RPE) cells, as compared with the 100,000-cell dose used in the previous three patients of the second cohort. The Stargardt’s Macular Dystrophy patient was treated at Bascom Palmer Eye Institute, while the patient with dry AMD was treated at another clinical trial site. ACT said both patients are recovering uneventfully.

New study for squalamine eye drops. The Elman Retina Group, Baltimore, MD, has filed a new clinical study protocol with the FDA using squalamine lactate eye drops for the treatment of retinal neovascularization associated with proliferative diabetic retinopathy. Endpoints include complete regression of neovascularization and mean change in visual acuity from baseline to five months.

B + L to distribute Leica surgical microscopes. Leica Microsystems said Bausch + Lomb will now distribute its ophthalmic surgical microscopes and accessories in select markets across Europe, the United States, India and Latin America.

The companies said the partnership combines the strength of Leica’s innovative ophthalmic microscopes with Bausch + Lomb’s global commercial infrastructure, expanding B + L’s offerings for ophthalmic surgeons. Under this agreement, Bausch + Lomb can now offer Leica Microsystems’ ophthalmic portfolio, including its high-end retinal systems. RP

Optomap Identifies More Retinal Lesions

The technology outperforms ophthalmoscopy.

■ A study comparing retinal imaging techniques in 339 eyes found that Optomap-assisted technology identified approximately 30% more retinal lesions than ophthalmoscopy.1 The study was conducted at the New England College of Optometry with results published in Eye and Brain.

Researchers investigated whether Optos’ (Marlborough, MA) ultra-wide-field retinal imaging technology could enable a more comprehensive exam. The accuracy of traditional dilated retinal exams has been reported in literature to vary from 32% to 82%.

The currently used traditional dilated eye exam consists of binocular indirect ophthalmoscopy (BIO) and slit lamp biomicroscopy with condensing lenses. The image-assisted method was identical to the traditional method, with the exception that investigators reviewed optomap images in conjunction with ophthalmoscopy. A retinal specialist examined patients when there was disagreement in the findings of the two methods.

Researchers believe this is the first comprehensive study to demonstrate the ability of digital technology for retinal imaging to enhance a traditional dilated fundus examination, concluding that Optomap image-assisted fundus examination enhances detection of retinal lesions compared with traditional fundus exams alone.

The analyses reported a higher rate of drusen and small retinal hemorrhages (lesions associated with macular degeneration and diabetic retinopathy respectively) detected by the Optomap image-assisted technique, identifying between 90%-100% in comparison to the traditional method that identified only 15%-62% of these lesions.

“Optomap image-assisted ophthalmoscopy represents an opportunity to improve pathology detection, the patient experience and to help a clinician efficiently target the area of the retina in need of further investigation,” said Roy Davis, CEO of Optos. This targeted approach, combined with the ability to electronically document pathologies, can save valuable time and effort during examinations, while also raising the standard of care.”


Brown K, Sewell JM, Trempe C, Peto T, Travison TG. Comparison of image-assisted versus traditional fundus examination. Eye Brain. 2013;2013:1–8.