At Press Time

Alcon Acquires “Femto-phaco” Technology

LenSx Deal: A key role for venture capital.

By Jerry Helzner, Senior Editor

■ LenSx Lasers, Inc., a leader in emerging “femto-phaco” technology, has a definitive agreement to be acquired by Alcon Labs. In the past year, LenSx has received three FDA clearances that permit its precise, computer-guided femtosecond laser technology to be used in various steps of the cataract removal procedure.

Alcon's entrance into femto-phaco represents more than just an endorsement of a potentially transformational technology. It also highlights the growing role of venture capital in advancing ophthalmology through the funding of numerous early-stage eyecare companies.

Until now, the development of the LenSx technology has been largely funded by four venture capital firms: Versant Ventures, SV Life Sciences, InterWest Partners and Venture Investors. Versant Ventures, InterWest and SV Life Sciences have been especially active in the ophthalmic sector, with each supporting the progress of multiple promising eyecare companies that are pursuing interesting concepts.

Though not all companies backed by venture capital become successful, the LenSx deal demonstrates the potential rewards that can accrue to investors who provide the seed money to develop new business ideas.

LenSx shareholders will receive $361.5 million in cash at closing for their shares, plus up to $382.5 million based upon the achievement and over-achievement of future femtosecond laser and procedure fee revenue milestones. The closing of the acquisition is subject to receipt of required regulatory approvals and customary closing conditions.

“This acquisition further strengthens patient choice in cataract surgery while offering new opportunities for ophthalmic surgeons and surgical centers worldwide,” said LenSx President and CEO, Ronald Kurtz, MD.

According to Stephen G. Slade, MD, who performed the initial series of LenSx laser procedures in the United States, “With this laser, we have seen a more exact size, shape and centration of the capsulotomy and precise centering of the intraocular lens, giving us the potential to deliver improved post-surgical refractive outcomes to our patients. I have also been able to reduce the energy required — further enhancing cataract surgery by providing a safe and more accurate refractive outcome.”

Two other companies, LensAR and OptiMedica, are also moving ahead in pursuing femto-phaco technology.

Vancomycin Effective in Cataract Surgery

But powerful antibiotic has a potential downside.

■ A long-term retrospective study of more than 16,000 cataract patients at a single surgical unit in England has determined that intracameral vancomycin is a highly effective prophylactic measure for almost eliminating postoperative endophthalmitis following cataract surgery. The study appeared in the April issue of Clinical Ophthalmology.

Critics of the study say that the overuse of vancomycin could render the drug less effective as resistance to it develops. They also point out that the antibiotics now commonly used in cataract surgery have proved effective, given the minimal incidence of endophthalmitis in the US.

The researchers evaluated 16,606 cataract surgeries performed over an almost 11-year period from January 1998 through December 2008. Between January 1998 and December 2000, a total of 3,904 cataract surgeries were performed using various anti-infectives and 13 patients developed endophthalmitis (0.3%). Then, an outbreak of endophthalmitis led to the introduction of intracameral vancomycin as the standard anti-infective for cataract surgery. From January 2001 through December 2008, 12,702 cataract surgeries were performed using intracameral vancomycin in a dose of 1mg in 0.1 mL of normal saline, injected into the capsular bag as the final step in surgery. Only one patient developed presumed endophthalmitis during this lengthy time period (0.008%).

Recent surveys of cataract surgeons in this country have shown that less than one surgeon in four routinely uses intracameral antibiotics. Most rely on topical antibiotics both pre- and postoperatively.

The researchers concluded that “intracameral vancomycin significantly reduced the incidence of postoperative endophthalmitis after cataract surgery. There is a universal need to adopt this mode of microbial prophylaxis to reduce the burden of endophthalmitis after cataract surgery.”

In the US, the powerful antibiotic vancomycin is typically used as a treatment for endophthalmitis and not as a preventive agent. It is used in this manner because of the possibility that the infection may be caused by a resistant organism such as MRSA.

Typical anti-infectives used in cataract surgery are intracameral cefuroxime or topical quinolones, gentamicin or polysporin/trimethoprim.

Glaucoma Patients and Alternative Therapies

What they don't tell their ophthalmologist.

■ Researchers from the University of Toronto and York University, also in Toronto, have found that a significant number of glaucoma patients are attempting to self-medicate with alternative therapies while keeping these efforts from their ophthalmologist. Their findings were presented at the recent ARVO meeting.

A total of 1,014 patients with glaucoma completed the survey, with 171 of these patients (16.9%) reporting current or past use of alternative medications specifically for glaucoma. Of these, 24% had informed their ophthalmologist of this use, but 66% had not informed their ophthalmologist and 10% had informed their ophthalmologist of some but not all of these alternative treatments.

Only 43.8% of the patients who had reported the use of alternatives believed that the treatments helped their glaucoma, 37.9% believed that these therapies were of no help and 18.3% were unsure.

The most commonly-used alternative therapies were herbal medications (32.5%) followed by dietary modifications (23.2%) and vitamin/mineral supplements (17.2%). Use of alternatives was associated with younger age at diagnosis, younger current age, longer duration of disease, higher education level, a history of prior surgical or laser treatments for glaucoma and subjectively greater impact of glaucoma on quality of life. Of the 131 patients who reported that they were currently using one or more alternative therapies for their glaucoma, only three (2.3%) indicated that they were using conventional glaucoma treatments less than prescribed because of their use of alternatives.

The researchers concluded that a significant proportion of glaucoma patients use alternative therapies for their disease. While most of these patients do not disclose this use to their ophthalmologist, the vast majority of patients still take conventional glaucoma medications as prescribed.

Positive Feedback on Toric IOLs

Survey finds high level of satisfaction.

■ Ophthalmology researchers from McGill University in Montreal conducted a telephone survey of 38 patients who had received the Alcon AcrySof Toric IOL (SN60T3) in both eyes in the 2008-2009 timeframe. The goal was to study the effect of correcting astigmatism on patient satisfaction. The positive results of the study were reported at the recent ARVO meeting.

The age of the responders ranged from 51 to 83 years, with a mean of 67. Thirty-six patients wore spectacles before the surgery but only seven reported wearing them after the surgery. Four of the responders said they wear the spectacles “all the time” and three patients “sometimes.”

Twenty-six patients gave a satisfaction score of 10, the highest on the satisfaction scale, seven graded a 9, three reported an 8 and only two patients graded less than 6.

Thirty-five patients reported no glare (0/4 on the glare scale), two reported 2/4 glare and one patient reported 3/4 glare. Thirty-six patients told the interviewers they would choose the same lens again while two said they would not.

The patients who wear glasses post-operatively, or gave a satisfaction score less than 6/10 or 3/4 on the glare scale, or who would not choose the same lens again have spherical refractive error (-1.5 to +1.25 D) and astigmatic error ranging from 0.25 D to 0.75 D.

The researchers concluded that implantation of the Alcon SN60T3 resulted in high spectacle independence postoperatively. Any need for glasses was due to spherical ametropia and not astigmatism. The researchers expect even greater patient satisfaction with higher cylinder correction (i.e., T4, T5).

Research Digest

New & Noteworthy Journal Articles

Compiled by Andrew E. Mathis, PhD, Medical Editor

► Banking on toric IOLs. How cost-effective are toric IOLs? A study published in the July 2010 issue of Archives of Ophthalmology sought to answer this question by developing a decision analytical model and applying it to patients with preoperative astigmatism undergoing phacoemulsification.

The research team, which consisted of researchers from the Massachusetts Eye and Ear Infirmary and the National Eye Institute, as well as from Abt Bio-Pharma Solutions, Inc., and Alcon Labs, tested their statistical model on patients at least 65 years old. They collected the cases both from a literature review and a survey of 60 US ophthalmologists.

The results indicated that a larger percentage of patients receiving toric IOLs achieved independence from spectacles for distance vision (67% vs. 63%) and uncorrected VA of 20/25 or better (53% vs. 48%). While these differences are relatively modest, difference in cost between patients receiving toric IOLs and those receiving conventional IOLs without intraoperative refractive correction was $349 per quality-adjusted life year per patient.

The authors of the study suggest that, when increased life expectancy is taken into account, the cost benefits over a lifetime of using toric IOLs could far exceed their greater price.

► A new DMEK. A team of surgeons in the Czech Republic have published a retrospective study of a new technique for corneal transplantation in the July 2010 British Journal of Ophthalmology. Dubbed DMEK-S, the technique involves the addition to the bare Descemet membrane of a supporting stromal ring 100 μm thick, 1 mm wide and 6 mm in diameter. This ring allows for marking of the anterior-posterior orientation of the lamellae, giving the surgeon better orientation. It also fixes the central portion of the graft, preventing scrolling of the membrane.

The case series undertaken consisted of 20 eyes in 18 patients with corneal endothelial dysfunction. Endothelial cell density and BCVA were measured at baseline and at a period of 12 to 24 months following DMEK-S. At follow-up, 18 had improved BCVA, which amounted to 100% of eyes that did not experience graft failure. Of these 18 eyes, all but one eye reached a Snellen BCVA of 0.5 or better, with the last eye not being followed up because of the patient's death.

The authors predict that increasing use of precut disks for DMEK will bear out even better results than those seen here.

► Dry eye QOL. While there has been a marked increase in awareness of dry eye disease over the last decade, data supporting the effectiveness of treatments on the basis of quality of life (QOL) measurements have been lacking. In an article in the July 2010 issue of Current Opinions in Ophthalmology Neil J. Friedman, MD, of the Stanford University School of Medicine, attempts to set the record straight.

Among the problems enumerated by Dr. Friedman is the lack of concordance between symptoms of — and diagnostic measures for — dry eye, such as Schirmer testing and fluorescein staining. Thus, he argues, QOL measurements may be the best way of measuring the burden of dry eye disease. Two QOL measurements specific to dry eye already exist: the Impact of Dry Eye on Everyday Life and the Ocular Surface Disease Index. Dr. Friedman then rated two dry eye treatments — cyclosporine ophthalmic solution and the Lacrisert insert — according to OSDI and a few non-OSDI criteria.

Mean improvement from baseline after insertion of Lacrisert resulted in statistically significant increases in QOL for reading, nighttime driving, computer or ATM work and watching television (all OSDI measurements), as well as reading, shopping and housework. The largest improvement was seen in performing tasks in heated areas. Cyclosporine patients experienced a large decrease in the extent to which dry eye symptoms affected their daily activities, although these results were not statistically significant.

Dr. Friedman asks researchers to take QOL into account in future studies of dry eye therapies, as such measurements are clearly relevant to effective treatment.

► Glaucoma terminology. Does glaucoma cause “thinning” or “narrowing” of the optic disc? That depends on the type of nerve-fiber loss, according to an article in the June/July 2010 issue of the Journal of Glaucoma.

Doctors at the Wills Eye Institute in Philadelphia conducted a literature review of 275 articles published in English and reviewed by at least one peer. Out of these articles, 80 described the effect of glaucoma on the neuroretinal rim, with 41 of them (51.25%) using the term “thinning” and 13 (16.25%) using “narrowing” as the descriptor. (The rest spoke of the optic disc in terms of changes in width.)

The second part of the Wills study was the surveying of 295 ophthalmologists at the annual meetings in 2006 of the Asia Pacific Association of Ophthalmology and the Albany (NY) Ophthalmology Update. These participants were asked to view two photographs of the same optic disc in which both the horizontal and vertical cup-disc ratios had decreased. Their terminology was then recorded. The overwhelming majority (264 ophthalmologists) used the term “thinner” rather than “narrower.”

While the study authors are able to draw some conclusions from their dual experiments, i.e., that “narrowing” is a better term for radial loss in width and “thinning” for decrease in thickness of the optic disc rim, they nevertheless call for the introduction of more precise terminology in the diagnosis and treatment of optic disc damage.

Retina Roundup

Timely and Important Retina News of Interest to All Ophthalmologists

Compiled by Andrew E. Mathis, PhD, Medical Editor

► Seeing the mountaintop. An alternative to monthly dosing with ranibizumab (Lucentis, Genentech) may be in the offing for those patients who either cannot afford the expensive treatments or who do not have regular access to a retinal specialist. Peter K. Kaiser, MD, of Cleveland Clinic's Cole Eye Institute presented June 8 in Berlin data from the phase 3b DENALI trial of a combination therapy of ranibizumab and verteporfin/PDT (Visudyne, Novartis).

The one-year data from the trial indicate that the combination of ranibizumab and verteporfin/PDT improved visual acuity by a mean of 5.3 letters in a standard-fluence cohort and 4.4 letters in a reduced-fluence cohort. This is in comparison to an average of 8.1 letters in the ranibizumab monotherapy arm. All cohorts received a three-month loading dose of ranibizumab.

However, the big difference was in the number of injections. Patients receiving combination therapy averaged 2.2 additional injections after loading (2.8 for the reduced-fluence group), while the monotherapy arm required 7.6 additional injections on average.

While the DENALI data have not yet been published, they should be appearing in print shortly.

► Optimizing photocoagulation. While panretinal photocoagulation is an effective treatment for diabetic retinopathy the common side effect of macular edema caused by PRP can be a significant cause of concern. A team of retinal physicians in South Korea tested intravitreal triamcinolone acetonide injections and bevacizumab (Avastin, Genentech) as adjuncts to PRP in the hopes of controlling post-laser macular edema. They reported their data in the July 2010 issue of the British Journal of Ophthalmology.

The study authors randomized 91 eyes of 76 patients with severe diabetic retinopathy — half with clinically significant macular edema and half without — into three arms: one receiving triamcinolone with PRP, one receiving bevacizumab with PRP and one receiving PRP only. Changes in central macular thickness and BCVA were measured at one and three months, as well as changes in acuity.

The PRP-only group experienced a statistically significant decline in BCVA (0.26 at month 1 to 0.29 at month 3), while the other two groups experienced no significant changes in VA. In eyes with macular edema, both triamcinolone and bevacizumab were correlated with decreases in central macular thickness.

These data seem to indicate that either triamcinolone or bevacizumab can be a worthwhile adjunct to PRP in preventing macular edema, though the authors do stress that triamcinolone appears to be the more effective of the two.

► AMD early detection. The July/August 2010 issue of Retina includes the report of a team of ophthalmologists, headed up in Tel Aviv, on a trial of a home-based preferential hyperacuity perimeter in early detection of choroidal neovascularization (CNV) secondary to AMD.

The device, developed by Notal Vision, Ltd. (Tel Aviv), was tested on 66 eyes in 65 patients in Israel and the United States. All eyes had intermediate AMD or newly diagnosed CNV The first part of the study required the participants, who were not supervised, to complete a retrospective questionnaire; in the second part, participants carried out a home test, with the results masked before computation. OCT and fluorescein angiography were performed on all participants within two weeks of the study.

When sensitivity and specificity measurements taken with OCT and fluorescein angiography were compared with the home testing, the results were nearly identical, indicating that the device can help distinguish with great accuracy the difference between intermediate AMD with and without CNV The team next intends to report on longer-term monitoring of patients with AMD, with this study already under way.

► Avastin in CRVO. With the recent approval of ranibizumab for macular edema following retinal vein occlusions, it is not surprising that bevacizumab has also been investigated for this disease. In the June 2010 issue of Retina, the two-year results of the Pan American Collaborative Retina Study Group's trial of bevacizumab for macular edema secondary to central retinal vein occlusion have been reported.

In the interventional, retrospective, comparative multicenter study of 86 eyes that received intravitreal injections of either 1.25 mg or 2.5 mg bevacizumab, approximately 57% of eyes improved three or more lines in ETDRS visual acuity. Furthermore, central retinal thickness decreased from 635 ±324 μm to 264 ±60 μm in the 1.25-mg group and 528 ±213 μm to 29 3±137 μm in the 2.5-mg. All these results were statistically significant. Notably, however, there was no statistically significant difference between the different dosage groups.

These results add to a growing number of studies showing the efficacy of bevacizumab in macular edema following retinal vein occlusions. The study's authors join the call for a prospective, blinded study to further investigate this intervention.

► More bad news about smoking. Unsurprisingly, there is new evidence of yet more eye problems tied to tobacco. In the July 2010 issue of the British Journal of Ophthalmology, a group of retinal physicians studying inflammatory disease, including uveitis, report that smoking is correlated with a higher rate of bilateral disease. Moreover, time to relapse was shorter in smokers and the rate of relapse was higher.

These findings add to the data suggesting that smoking is a factor in higher rates of scleritis and episcleritis. OM