Volume 14, Number 16
Monday, April 21, 2014

In this issue: (click heading to view article)
######### Sporadic VA Loss in the Comparison of Age-Related Macular Degeneration Treatment Trials

######### Markers of Inflammation, Oxidative Stress, Endothelial Dysfunction and 20-Year Cumulative Incidence of Early AMD
######### Factors Influencing the Exudative Recurrence Following Cataract Surgery in Patients Previously Treated with Anti-VEGF for Exudative AMD
######### Association Between In Vitro Susceptibility to Natamycin and Voriconazole and Clinical Outcomes in Fungal Keratitis
######### Briefly

Sporadic VA Loss in the Comparison of Age-Related Macular Degeneration Treatment Trials

In a cohort within a randomized clinical trial (the Comparison of AMD Treatments Trials [CATT]), investigators evaluated transient, large visual acuity (VA) decreases, termed sporadic vision loss, during anti-vascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (AMD).

Included were 1,185 CATT patients. Incidence of sporadic vision loss and odds ratio (OR) for association with patient and ocular factors were the main outcome measures. Sporadic vision loss was a decline of ≥ 15 letters from the previous visit, followed by a return at the next visit to no more than five letters worse than the visit before the VA loss.

The investigators reported that there were 143 sporadic vision loss events in 122/1,185 (10.3%) patients. They also noted that mean VA at two years for those with and without sporadic vision loss was 58.5 (~20/63) and 68.4 (~20/40) letters, respectively (p<0.001). Among patients treated pro re nata, no injection was given for 27.6% (27/98) of sporadic vision loss events. Multivariate analysis demonstrated that baseline predictors for sporadic vision loss included worse baseline VA (OR 2.92, 95% CI:1.65 to 5.17 for ≤ 20/200 compared with ≥ 20/40), scar (OR 2.21, 95% CI:1.22 to 4.01), intraretinal foveal fluid on optical coherence tomography (OR 1.80, 95% CI:1.11 to 2.91), and medical history of anxiety (OR 1.90, 95% CI:1.12 to 3.24) and syncope (OR 2.75, 95% CI:1.45 to 5.22). Refraction decreased the likelihood of sporadic vision loss (OR 0.62, 95% CI:0.42 to 0.91).

Approximately 10% of CATT patients had sporadic vision loss. Baseline predictors included AMD-related factors and factors independent of AMD. These data are relevant for clinicians in practice and those involved in clinical trials.

SOURCE: Kim BJ, Ying GS, Huang J, et al; on behalf of the CATT Research Group. Sporadic visual acuity loss in the comparison of age-related macular degeneration treatments trials (CATT). Am J Ophthalmol. 2014; Apr 10 [Epub ahead of print].

Markers of Inflammation, Oxidative Stress, Endothelial Dysfunction and 20-Year Cumulative Incidence of Early AMD

Modifying levels of factors associated with age-related macular degeneration (AMD) may decrease the risk for visual impairment in older persons. This longitudinal population-based cohort study examined the relationships of markers of inflammation, oxidative stress and endothelial dysfunction to the 20-year cumulative incidence of early AMD. It involved a random sample of 975 persons in the Beaver Dam Eye Study without signs of AMD who participated in the baseline examination in 1988 to 1990 and up to four follow-up examinations in 1993 to 1995, 1998 to 2000, 2003 to 2005, and 2008 to 2010.

Serum markers of inflammation (high-sensitivity C-reactive protein, tumor necrosis factor [TNF]–α receptor 2, interleukin-6, and white blood cell count), oxidative stress (8-isoprostane and total carbonyl content), and endothelial dysfunction (soluble vascular cell adhesion molecule [VCAM] ]–1 and soluble intercellular adhesion molecule]–1) were measured. Interactions with complement factor H (rs1061170), age-related maculopathy susceptibility 2 (rs10490924), complement component 3 (rs2230199), and complement component 2/complement factor B (rs4151667) were examined using multiplicative models. AMD was assessed from fundus photographs. The main outcome measure was early AMD defined by the presence of any size drusen and the presence of pigmentary abnormalities or by the presence of large-sized drusen (≥125-µm diameter) in the absence of late AMD.

It was determined that the 20-year cumulative incidence of early AMD was 23.0%. Adjusting for age, sex, and other risk factors, high-sensitivity C-reactive protein (odds ratio [OR] comparing fourth with first quartile, 2.18; p=0.005), TNF–α receptor 2 (OR, 1.78; p=0.04), and interleukin-6 (OR, 1.78; p=0.03) were associated with the incidence of early AMD. Additionally, increased incidence of early AMD was associated with soluble VCAM–1 (OR per SD on the logarithmic scale, 1.21; p=0.04).

Modest evidence of relationships of serum high-sensitivity C-reactive protein, TNF–α receptor 2, interleukin-6, and soluble VCAM–1 to the 20-year cumulative incidence of early AMD independent of age, smoking status, and other factors was found. It is not known whether these associations represent a cause-and-effect relationship or whether other unknown confounders accounted for the findings. Even if inflammatory processes are a cause of early AMD, it is not known whether interventions that reduce systemic inflammatory processes will reduce the incidence of early AMD.

SOURCE: Klein R, Myers CE, Cruickshanks KJ, et al. Markers of inflammation, oxidative stress, and endothelial dysfunction and the 20-year cumulative incidence of early age-related macular degeneration. The Beaver Dam Eye Study. JAMA Ophthalmol. 2014;132(4):446–455.

Factors Influencing the Exudative Recurrence Following Cataract Surgery in Patients Previously Treated with Anti-VEGF for Exudative AMD

To investigate factors influencing exudation recurrence following cataract surgery in patients already treated with anti-vascular endothelial growth factor (VEGF) agents for exudative age-related macular degeneration (AMD), researchers performed a retrospective review of medical records for patients who underwent cataract surgery and had been previously treated with anti-VEGF for exudative AMD. Visual acuity was examined before surgery and one and six months following surgery. The time between diagnosis and surgery, and the exudation-free period before surgery were examined and compared between patients who had exudation recurrence and those that did not.

A total of 39 eyes of 39 patients were included in analyses. According to the researchers, the logarithm of the minimum angle of resolution visual acuity was 1.02 ± 0.58 and had significantly improved one month (0.81 ±  0.62, p<0.001) and six months (0.85 ±  0.64, p=0.001) following surgery. They also found that both the diagnosis-to-surgery period (p=0.001) and the preoperative exudation-free period (p<0.001) were significantly longer in patients without recurrence than in patients with recurrence.

According to the researchers, vitamins B6 and B12 intake was not associated with EG/SEG risk in pooled analyses (p=0.52 and p=0.99 for linear trend, respectively). However, they observed a suggestive trend of a reduced risk with higher intake of folate: compared with the lowest quintile of cumulatively averaged updated total folate intake, the multivariable relative risk for EG/SEG for the highest quintile (≥654 µg/d) was 0.75 (95% CI, 0.54 to 1.04; p=0.02 for linear trend). These results were not materially altered after adjustment for vitamins B6 and B12 intake. The study researchers observed an association for supplemental folate intake, but not for dietary folate only (p=0.03 and p=0.64 for linear trend, respectively). Greater frequency of multivitamin use showed a modest suggestive inverse association (current multivitamin use of ≥6 times per week vs. nonuse multivariable relative risk, 0.84; 95% CI, 0.64 to 1.11; p=0.06 for linear trend).

In conclusion, cataract surgery was beneficial in patients previously treated with anti-VEGF for exudative AMD. These data suggest that cataract surgery should be performed after a sufficiently long exudation-free period to minimize exudation recurrence; however, larger prospective studies are required to draw definitive clinical guidelines.

SOURCE: Lee TG, Kim JH, Chang YS, et al. Factors influencing the exudation recurrence after cataract surgery in patients previously treated with anti-vascular endothelial growth factor for exudative age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2014; April. [Epub ahead of print].

Association Between In Vitro Susceptibility to Natamycin and Voriconazole and Clinical Outcomes in Fungal Keratitis

The authors of the following experimental study used data from a randomized comparative trial to assess the association between minimum inhibitory concentration (MIC) and clinical outcomes in a fungal keratitis clinical trial.

Of the 323 patients enrolled in the trial, the authors were able to obtain MIC values from 221 patients with monocular fungal keratitis. The Mycotic Ulcer Treatment Trial I was a randomized, double-masked clinical trial comparing clinical outcomes of monotherapy with topical natamycin versus voriconazole for the treatment of fungal keratitis. The study authors performed speciation and determination of MIC to natamycin and voriconazole according to Clinical and Laboratory Standards Institute guidelines. They also assessed the relationship between MIC and clinical outcome. The primary outcome was three-month best spectacle-corrected visual acuity. Secondary outcomes included three-month infiltrate or scar size; corneal perforation and/or therapeutic penetrating keratoplasty; and time to re-epithelialization.

A two fold increase in MIC was associated with a larger three-month infiltrate or scar size (0.21 mm; 95% confidence interval [CI], 0.10 to 0.31; p<0.001) and increased odds of perforation (odds ratio [OR], 1.32; 95% CI, 1.04 to 1.69; p=0.02). The authors found no correlation between MIC and three-month visual acuity. For natamycin-treated cases, they found an association between higher natamycin MIC with larger three-month infiltrate or scar size (0.29 mm; 95% CI, 0.15 to 0.43; p<0.001) and increased perforations (OR, 2.41; 95% CI, 1.46 to 3.97; p<0.001). Among voriconazole-treated cases, the voriconazole MIC did not correlate with any of the measured outcomes in the study.

To conclude, decreased susceptibility to natamycin was associated with increased infiltrate or scar size and increased odds of perforation. There was no association between susceptibility to voriconazole and outcome.

SOURCE: Sun CQ, Lalitha P, Prajna NV, et al.; Mycotic Ulcer Treatment Trial Group. Association between in vitro susceptibility to natamycin and voriconazole and clinical outcomes in fungal keratitis. Ophthalmology. 2014;Apr 16. [Epub ahead of print].

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  • JJVCI NOW ACCEPTING RESEARCH PROPOSALS ON MEIBOGRAPHY AND TEAR FILM STABILITY WITH CONTACT LENS WEAR. Johnson & Johnson Vision Care (JJVCI) is currently accepting research proposals related to meibography and tear film stability with contact lens wear. Specific areas of interest include correlating clinical findings (i.e., lid wiper epitheliopathy, subjective symptoms, physiology) to meibomian gland image analysis and tear film stability, as well as categorizing magnitude of meibomian gland changes to contact lens type or length of wear. Proposals must be submitted in English through the JJVCI Investigator Initiated Study application process by contacting the Clinical Research Administrator via email or phone (904-443-1525).

  • PDUFA DATE FOR ILUVIEN ANNOUNCED. According to pSivida Corp., the FDA has established a Prescription Drug User Fee Act (PDUFA) goal date of September 26, 2014 for Iluvien following the recent submission of the New Drug Application by pSivida's licensee, Alimera Sciences.
  • NEW DELUXE KIT FROM MENICON. Menicon America Inc. has a new kit available for getting patients started on the Menicon GP solutions system. It consists of a 60-mL bottle of Menicon Unique pH, a lens case, and a single-treatment package of Progent bi-weekly cleaner, which all come packaged in a TSA-compliant clear plastic travel case. The Menicon Deluxe Kit is available to eye-care professionals exclusively through the Menicon WebStore.
  • RPS EXPANDS ORGANIZATION IN RESPONSE TO GROWING DEMAND FOR INFLAMMADRY. Rapid Pathogen Screening Inc. (RPS) announced the expansion of its eye-care organization to meet the growing demand for its in-office dry-eye test, InflammaDry. Specifically, the company has established a focused eye-care sales and marketing team with extensive industry experience to lead the global commercial efforts. Additionally, RPS has entered into a U.S. co-promotional partnership with Allergan Inc. to increase awareness of dry-eye disease related to elevated matrix metallopeptidase 9 in tears.
  • ALCON OPENS NEW OPHTHALMIC PHARMACEUTICAL MANUFACTURING PLANT IN SINGAPORE. Alcon has opened the doors to its new, 330,000-square-foot, state-of-the-art ophthalmic pharmaceutical manufacturing facility in the Tuas Biomedical Park in Singapore, allowing the company to be closer and quickly respond to its growing base of customers and patients throughout Asia. The plant, which currently employs approximately 150 associates, produces ophthalmic pharmaceutical products that address eye conditions such as glaucoma, dry eye, allergies and bacterial infections. Get more details here.
  • iSTAR SIGNS AGREEMENT WITH I-T-D FOR DISTRIBUTION OF GLAUCOMA IMPLANT IN GERMANY. iSTAR Medical SA has signed an exclusive distributor agreement with Innovative Therapie und Diagnostik GmbH (I-T-D) stating that I-T-D will distribute the STARflo Glaucoma Implant on an exclusive basis in Germany. STARflo is a nondegradable, precision-pore implant made from STAR Biomaterial and is designed to operate as a bleb-free, micro-porous drainage system to reduce intraocular pressure in patients suffering from open-angle glaucoma by augmenting the eye's natural uveoscleral outflow. STARflo will enter its first multi-country (EU-USA) clinical study this year, according to iSTAR. Read more at www.istarmed.com.

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