The Food and Drug Administration last month approved Alcon's Travatan Z (travoprost ophthalmic solution) 0.004% for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension, who are intolerant of or insufficiently responsive to other IOP-lowering medications.
Travatan Z is a new formulation that eliminates benzalkonium chloride from Alcon's existing Travatan solution and replaces BAK with Sofzia, a robust ionic buffered preservative system that is gentle to the ocular surface. Alcon developed this BAK-free version of Travatan because long-term use of topical solutions containing BAK may compromise the ocular surface and exacerbate conditions such as dry eye.
"Because almost 40 percent of glaucoma patients suffer from ocular surface disease, Travatan Z is an advance in therapy which we believe will now enable doctors to address an unmet need of many glaucoma patients," said Kevin Buehler, Alcon's senior vice president, United States and chief marketing officer.
FDA approval of Travatan Z solution was based on a double-masked, multicenter study, which has been accepted for publication by the Journal of Glaucoma. The 690 adult patients with open-angle glaucoma or ocular hypertension were randomized to receive Travatan or Travatan Z. Travatan Z reduced IOP up to 8.5 mmHg on average demonstrating statistically equivalent IOP lowering efficacy to the original Travatan. Similar adverse events were noted in both groups.
"These data demonstrate that Travatan Z is equally effective in reducing intraocular pressure in glaucoma patients compared to Travatan with BAK," said Rick Lewis, MD, lead investigator of this study. "However, chronic use of Travatan Z is less likely to compromise the ocular surface, potentially reducing eye irritation in glaucoma patients also suffering from ocular sensitivities."
TASS Task Force Reports Findings
A task force sponsored by the American Society of Cataract and Refractive Surgery issued its final report following an investigation into an outbreak of Toxic Anterior Segment Syndrome (TASS) in early 2006.
From January to July 2006, 113 centers reported cases of TASS, with reports peaking in April 2006. The reports have since decreased to what is considered a baseline level. While the Task Force will continue to evaluate potential etiologic factors involved in TASS, it appears as though the early 2006 outbreak has subsided significantly. In the majority of cases involved in this outbreak, the degree of inflammation was rated as moderate. Fortunately, the majority of patients have recovered good visual acuity without significant ocular sequelae. Unfortunately, a small group of patients had more severe inflammation and have ongoing ocular problems from the toxic insult.
There were no conclusive epidemiologic data to suggest that any one product or single cause was responsible for the increase in TASS cases. Thorough analysis of the data provided has revealed multiple potential etiologic factors that could be involved. The cleaning and sterilization of instruments for cataract surgery appears to be the most important factor involved in many of the cases reviewed.
The results of this investigation were shared with representatives of the FDA and the CDC. Among the key areas of investigation and findings:
• The use of reusable, cannulated instruments of any kind is a potential source of TASS. Ultrasound hand pieces and similar hand pieces used for irrigation and aspiration may be a potential source of material that can incite inflammation. Several centers reported "occluded I/A tips," which raises the issue of proper flushing of hand pieces and tips between cases. It is imperative that all reusable hand pieces and cannulas be flushed thoroughly (and immediately at the conclusion of the case). Seven centers reported reuse of phaco tubing; the use of single-use devices where no instructions are provided by the manufacturer should be prohibited unless validated. Devices designed for single use should not be reused.
The Task Force recommends the use of sterile, deionized/distilled water for flushing. Most manufacturers of phacoemulsification hand pieces similarly recommend flushing of both the irrigation and aspiration ports of phacoemulsification and I/A hand pieces with specified volumes of sterile, deionized/distilled water at the conclusion of the case. Inadequate flushing may allow a build up of residual cortex, viscoelastic and other materials on the inside of the phacoemulsification or I/A hand pieces that could conceivably cause TASS. All reusable cannulas should be thoroughly flushed immediately following the conclusion of the previous case to avoid any residual material left within the cannulas. Disposable cannulas are recommended whenver possible in these surgical cases and should not be reused.
• Cleaning of instruments between cases with the use of water baths, enzymes or detergents. If any of the materials in these solutions are not properly rinsed from the instruments, the residual material may cause TASS. This issue has become especially important at centers where ophthalmologic instruments are cleaned with enzymatic detergents and ultrasound alongside instruments used in non-ophthalmologic surgery.
If these steps are to be undertaken with ophthalmic surgical instruments, it is critical that instruments be thoroughly rinsed with sterile, deionized/ distilled water at the conclusion of any treatments with these solutions to remove any residual detergent or enzyme. Autoclaving will not deactivate any enzyme or detergent.
• The use of ultrasound water baths to clean instruments between cases as a potential contamination of the water bath with gram-negative bacteria. Growth of these bacteria with subsequent endotoxin production could cause contamination of the instruments. The endotoxin is very heat-stable and will survive autoclaving and may cause TASS, even after the bacteria is incapacitated by the heat from the autoclave. Ultrasound baths should be emptied and thoroughly cleaned after each use or at least at the end of each day.
• The possibility of contamination within the steam sterilizer itself. The filters, water chambers and inside of autoclave units should be thoroughly cleaned according to manufacturers recommendations on a regular basis to prevent the possibility of contamination by endotoxin within the sterilizer itself, as well as any material coming from the water supply for the steam sterilizer.
• Additives to any of the solutions or medications going into the eye at any point of the surgery should be preservative-free. One potential problem is epinephrine, which is added to the balanced salt solution to maintain pupilary dilation during phacoemulsification. Not only must the epinephrine be preservative-free, it should also be free of stabilizing agents such as bisulphites or metabisulphites. Although these are not considered to be traditional preservatives, they are toxic to the corneal endothelium as well as other cells within the anterior segment of the eye and can lead to TASS.
• The issue of intracameral anesthetics was found to be a potential factor related to TASS. This is especially important in the era of very efficient phacoemulsification with a very short ultrasound time in the majority of cases leaving the possibility that anesthetic may remain in the anterior chamber of the eye and not be adequately diluted and flushed out at the conclusion of the case. As with other additives, it is important that the anesthetic be preservative free. Also, the dosage of the anesthetic is important; the anesthetic should not be highly concentrated when it is injected into the anterior chamber of the eye. A final factor is the possibility that viscoelastic may also potentiate the length of time the anesthetic can remain in the anterior chamber of the eye.
• The use of intracameral antibiotics was also addressed, and no specific problems were found. However, it remains extremely important that the antibiotic be properly mixed or reconstituted, as well as properly dosed for injection into the anterior chamber of the eye. A high dose of antibiotic has the potential to cause toxicity within the anterior segment.
• No single type of intraocular lens was found to be exclusive to the TASS syndrome. Intraocular lenses from three major IOL manufacturers in the United States were found in these cases and seem to represent market share of the lenses in the centers involved.
The Task Force will continue to evaluate data that is submitted and will also continue meeting regularly by conference call. The group hopes to help in the establishment of formal guidelines regarding the cleaning and sterilization of ophthalmic surgical instruments. For the full report, visit acrcs.org.
AMD Drugs' Progress Reported At ASRS Meeting
The September meeting of the combined American and European Societies of Retina Specialists featured several reports updating trials of macular degeneration drugs.
Two-year results were presented from the MARINA study, a two-year Phase III clinical study of 716 patients with minimally classic or occult wet AMD randomized to receive 0.3 mg, 0.5 mg or sham injection of intravitreal ranibizumab (Lucentis, Genentech) for 24 months. Of the 716, 683 or 95 percent continued into the second year of treatment. The two-year results, by dosage group:
• In the 0.3-mg treatment group, 92 percent of patients lost <15 letters of best corrected visual acuity; there was a mean improvement in BCVA of 5.4 letters; 26.1 percent gained >15 letters; and there was an 8.4-percent incidence of serious ocular adverse events (which were similar for all three groups).
• In the 0.5-mg treatment group, 95 percent of patients lost <15 letters of best corrected visual acuity; there was a mean improvement in BCVA of 6.6 letters; 33.3 percent gained >15 letters; and there was an 8.8-percent incidence of serious ocular adverse events.
• In the sham group, 52.9 percent of patients lost <15 letters of BCVA; there was a mean loss in BCVA of 14.9 letters; 3.8 percent gained >15 letters; there was an 7.2 percent incidence of serious ocular adverse events.
The researchers report that ranibizumab treatment prevented growth of CNV lesions, decreased the area of leakage and was well-tolerated.
Combining data from three (MARINA, ANCHOR and PIER) studies of ranibizumab, researchers looked at the effect of two dosages (0.3 and 0.5 mg) on contrast sensitivity. Mean change from baselines in contrast sensitivity at 12 months by Pelli-Robson chart was measured. At 12 months, both dosages of ranibizumab increased contrast sensitivity by a mean of approximately two letters in MARINA, by three letters in the 0.3-mg arm of the ANCHOR study and by four letters in the 0.5-mg arm of ANCHOR. In the sham treatment groups of MARINA and the PDT group of ANCHOR, contrast sensitivity decreased by a mean of three letters at 12 months.
A retrospective analysis of the pegaptanib (Macugen, OSI/Eyetech) VEGF Inhibition Study In Ocular Neovascularization (VISION) data suggested that early detection and treatment may result in improved vision outcomes for wet AMD patients. When looking at the results for patients with early lesions:
• The mean vision change from baseline to week 54 was -4 letters for Macugen-treated patients versus -16.7 letters for those in usual care.
• The proportion of patients gaining ≥ 3 lines of vision was 20 percent [6/30] in the Macugen 0.3-mg group vs. none [0/35] in the usual care group.
• Patients who received usual care were twice as likely to experience severe vision loss than those treated with Macugen (23 percent [8/35] vs. 10 percent [3/30], respectively).
A retrospective review of patient data in 90 newly diagnosed neovascular AMD patients undergoing treatment with Macugen as primary therapy showed:
• Ninety percent (81/90) of patients had stabilization or improved vision: 20 percent (18/90) gained > 3 lines of Snellen visual acuity and 70 percent (63/90) had stabilized vision (defined as no change + 2 lines). Only 10 percent (9/90) of patients reported loss of > 3 lines of vision.
