Volume 12, Number 10
Monday, March 5, 2012


In this issue: (click heading to view article)
######### AMD Analysis Reveals Global Biomarkers and Phenotype-Specific Functional Networks

######### Visual Outcomes Following DSAEK
######### Impact of Long-Term Topical Anti-Glaucoma Medications on Meibomian Glands
######### A Look at Serious Ocular Complications of Cosmetic Iris Implants
######### Briefly



AMD Analysis Reveals Global Biomarkers and Phenotype-Specific Functional Networks

Investigators sought to better understand the molecular underpinnings of age-related macular degeneration (AMD) by performing the first comparative transcriptome analysis of AMD and normal human donor eyes.

They obtained retinal pigmented epithelium (RPE)-choroid and retina tissue samples from a common cohort of 31 normal, 26 AMD and 11 potential pre-AMD human donor eyes. They also generated transcriptome profiles for macular and extramacular regions, and employed statistical and bioinformatic methods to identify disease-associated gene signatures and functionally enriched protein association networks. They validated selected genes of high significance using an independent donor cohort.

The study investigators identified more than 50 annoted genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, they show that the top 20 global genes are predictive of AMD clinical diagnosis. They also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, they identified a graded increase of transcript levels in the retina related to wound response, complement cascade and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on their findings, the investigators assembled protein-protein interactomes that highlight functional networks likely to be involved in AMD pathogenesis.

They discovered new global biomarkers and gene expression signatures of AMD. These results are consistent with a model whereby cell-based inflammatory responses represent a central feature of AMD etiology, and depending on genetics, environment or stochastic factors, may give rise to the advanced AMD phenotypes characterized by angiogenesis and/or cell death. Genes regulating these immunological activities, along with numerous other genes identified here, represent promising new targets for AMD-directed therapeutics and diagnostics.

SOURCE: Newman AM, Gallo N, Hancox LS, et al. Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks. Genome Medicine. 2012;4:16.


Visual Outcomes Following DSAEK

This retrospective analysis of a noncomparative, interventional case series evaluated the long-term improvement of visual acuity after Descemet's stripping automated endothelial keratoplasty (DSAEK) surgery.

A total of 108 patients undergoing DSAEK surgery for Fuchs' endothelial dystrophy and pseudophakic bullous keratopathy without other ocular comorbidities who completed a full 3-year follow-up period were included.

Postoperative best spectacle-corrected visual acuity (BSCVA) was recorded at 6, 12, 24 and 36 months and improvement in BSCVA between each time point was evaluated using paired-samples t tests. Additionally, subanalysis evaluating the percentage of eyes achieving a BSCVA of 20/20, 20/25, 20/30, and 20/40 at each time point was performed. The main outcome measure was improvement in postoperative BSCVA.

It was reported that there was a statistically significant trend toward improvement in average BSCVA with time at postoperative month 6 and postoperative years 2 and 3. There were also increasing proportions of eyes reaching vision of 20/20, 20/25 and 20/30 from 6 months to 1 year, 1 year to 2 years, and 2 years to 3 years. The percentage of patients achieving 20/25 BSCVA improved from 36.1% at 6 months to 70.4% at 3 years after surgery. A similar increase in the percentage of patients reaching a BSCVA of 20/20 after DSAEK surgery also was observed from 11.1% at 6 months to approximately 47.2% at 3 years.

To conclude, there is gradual improvement of visual acuity over time after DSAEK surgery for Fuchs' endothelial dystrophy and pseudophakic bullous keratopathy in patients without other vision-limiting ocular comorbidities.

SOURCE: Li JY, Terry MA, Goshe J, et al. Three-year visual acuity outcomes after Descemet's stripping automated endothelial keratoplasty. Ophthlamol. 2012;Feb. 27 [Epub ahead of print].

Impact of Long-Term Topical Anti-Glaucoma Medications on Meibomian Glands

Japanese researchers conducted a cross-sectional observational case series to examine effects of long-term topical anti-glaucoma medications on meibomian gland morphology and function and assess their relationship with slit-lamp findings.

They looked at 31 patients with glaucoma (mean age ± standard deviation, 65.0 ± 13.0 years; mean duration of eye drop use, 7.9 ± 6.0 years) treated with topical anti-glaucoma drugs in only one eye for more than 1 year: 13 receiving prostaglandin analogues (PGs) alone, eight receiving β-blockers alone, and 10 receiving multiple treatments. Untreated contralateral eyes served as controls. The researchers observed lid margin (lid margin abnormality score 0–4) and superficial punctate keratopathy (SPK score: 0–1) with a slit lamp. They also turned over upper and lower eyelids to observe meibomian glands using non-contact meibography and scored meibomian gland loss for each eyelid from grade 0 (no loss of meibomin glands) through grade 3 (loss >2/3 of total meibomian gland area). Finally, they scored meibomian lipid content (meibum)(meibum score: 0–3).

The study researchers reported that treated eyes had significantly higher scores for lid margin abnormality (p=0.001), SPK (p<0.001), meibo-score (p<0.001) and meibum (p<0.001) than control eyes. Tear film break-up time (BUT) was significantly shorter in treated eyes than in control eyes (p=0.001) and Schirmer values were significantly lower in treated eyes than in control eyes (p=0.0039). Furthermore, subgroup analysis indicated a significantly higher meibo-score in eyes treated with PGs (p=0.0046) and in eyes treated with β-blockers (p=0.0231) than in the corresponding controls.

Long-term anti-glaucoma eye drop use affects meibomian gland morphology and function.

SOURCE: Arita R, Itoh K, Maeda S, et al. Effects of long-term topical anti-glaucoma medications on meibomian glands. Graefes Arch Clin Exp Ophthalmol. 2012; Feb. 18 [Epub ahead of print].


A Look at Serious Ocular Complications of Cosmetic Iris Implants

The authors of the following case series reported the presentation and subsequent management of a series of patients presenting with cosmetic iris implants.

In this evaluation of patients with newColorIris cosmetic iris implants, data collected included patient demographics, visual acuity, intraocular pressure (IOP), endothelial cell count and slit lamp examination findings at presentation. The study authors recorded medical and surgical interventions and the postoperative course.

They identified 14 eyes of 7 patients (ages 22 to 60; 71% men) and reported that nine eyes (64%) presented with decreased visual acuity, 7 (50%) had elevated IOP, 5 (36%) had corneal edema and 5 (36%) had anterior uveitis. They also noted that all 14 eyes had explantation of the iris prosthesis (range 4 to 33 months after placement). The minimum follow up after implant removal in all eyes was 2 months (range 2 to 28 months). Intraoperative complications included suprachoroidal hemorrhage during explantation in 1 eye, while postoperative complications included corneal edema (8 eyes), cataract (9 eyes) and increased IOP/glaucoma (7 eyes). Secondary surgeries included Descemet-stripping automated endothelial keratoplasty (5 eyes), cataract extraction with intraocular lens placement (7 eyes), trabeculectomy (3 eyes), glaucoma drainage implant placement (3 eyes) and penetrating keratoplasty (1 eye).

In conclusion, the cosmetic iris implants may result in severe ocular morbidity. Complications in this series included uveitis, glaucoma, corneal edema and decreased visual acuity. Although explantation helped stabilize symptoms, additional medical and surgical intervention to control IOP and corneal decompensation was required in many cases.

SOURCE: Hoguet A, Ritterband D, Koplin R, et al. Serious ocular complications of cosmetic iris implants in 14 eyes. J Cataract Refract Surg. 2012;38(3):387–393.



  • QLT SHARES POSITIVE PRELIMINARY RESULTS FROM PHASE 1b TRIAL OF QLT091001 IN RP. QLT Inc. recently announced positive preliminary results from its international multi-center Phase 1b proof-of-concept clinical trial of QLT091001 for the treatment of retinitis pigmentosa (RP) due to inherited genetic mutations in retinal pigment epithelium protein 65 (RPE65) or lecithin:retinol acyltransferase (LRAT, also known as early-onset RP). In the open-label, multi-center Phase 1b clinical study, 17 subjects (ranging in age from 6 to 55 years, mean 29 years) with either RPE65 (12 subjects) or LRAT (5 subjects) mutations received a 40 mg/m²/day dose of QLT091001 once daily for seven days with post-treatment follow-up at 7, 14 and 30 days. The study showed rapid, statistically significant and clinically meaningful changes in visual fields from baseline values, as well as improvements in visual acuity. After a single 7-day course of treatment with QLT091001, the average retinal areas from baseline showed statistically significant improvement of 23% at day 30 (p=0.07) in the evaluable subjects meeting Goldmann Visual Fields test criteria (n=14 subset).
  • PHASE III STUDY OF EGP-437 FOR ANTERIOR UVEITIS INITIATED. EyeGate Pharma has enrolled the first patient in a milestone Phase III pivotal study of its lead product EGP-437 (a late-stage asset with multiple indications for inflammatory ocular indications), for the treatment of anterior uveitis. EyeGate says the randomized double-masked positive-controlled non-inferiority study will enroll up to 200 subjects at more than 20 U.S. sites to assess the effectiveness of EGP-437 in comparison to topically applied prednisolone acetate eye drops. The drug will be administered using the company's non-invasive iontophoretic drug delivery technology, the EyeGate II Drug Delivery System. The Phase II study results, published in the January 2012 issue of Ophthalmology, revealed that roughly two-thirds of the patients reached an anterior chamber cell score of zero within 28 days, after only receiving on iontophoresis treatment. No changes in IOP or signs of cataract formation were detected. Click here for additional information.
  • ACUVUE 1-DAY MOIST BRAND CONTACT LENSES FOR ASTIGMATISM LAUNCHED. At this year's Southeastern Council of Optometry (SECO) International Congress, Vistakon Division of Johnson & Johnson Vision Care, Inc. announced the U.S. launch of 1-Day Acuvue Moist Brand Contact Lenses for Astigmatism, a new daily disposable soft toric contact lens for individuals with astigmatism. In addition to the health and convenience benefits of wearing a fresh contact lens every day, 1-Day Acuvue Moist for Astigmatism features a proprietary Blink Stabilized Design that helps keep the lens in place and quickly realign it if it rotates out of position, providing wearers with consistent, all-day vision. According to Vistakon, 1-Day Acuvue Moist for Astigmatism are made using Lacreon Technology, a unique process that permanently embeds a water holding ingredient, similar to that found in natural tears, into the proven etafilcon A material of the 1-Day Acuvue Brand. Visit www.jnjvisioncare.com for additional information.
  • ADDITIONAL RANGE OF POWERS ADDED TO B+L'S PUREVISION 2 HD FOR ASTIGMATISM LINE OF CLS. Bausch + Lomb is expanding the range of powers to its PureVision2 for Astigmatism line of contact lenses. The line is currently available in plano to –6.00D (.25D steps) sphere power, and –0.75, –1.25D, –1.75 cylinder powers and the expanded range will be launched in two waves. According to Bausch + Lomb, the first wave, launched on March 1, 2012, extends the sphere powers offered to plano to –9.00D (.50D steps above –6.00D), and cylinder powers of –0.75D, –1.25D, –1.75D and –2.25D in 10° increments around the clock. The second wave, planned for May 1, will add plus powers up to +6.00D (.25D steps) to the range. The entire range will be available in the same four cylinder powers, –0.75D, –1.25D, –1.75D, to –2.25D in 10° increments around the clock. For more, click here.
  • OCuSOFT LENS CARE SYSTEM NOW AVAILABLE. OCuSOFT, Inc. has entered into a joint venture agreement with Essentia Pharma, LLC to introduce and market the OCuSOFT Lens Care System for soft contact lenses. OCuSOFT says that its cleaning system's convenient 3-in-1 system deep cleans, stores and disinfects with the efficacy of 3% hydrogen peroxide while ensuring comfort with a lubricating agent and no added preservatives. Special discount pricing is available to doctors for dispensing from their office; however, patients may order direct at www.ocusoft.com.
  • POSITIVE OUTCOME ANNOUNCED TO THE EUROPEAN DECENTRALIZED PROCEDURE FOR APPROVAL OF ILUVIEN FOR THE TREATMENT OF CHRONIC DME. Following the issuance of the Final Assessment Report from the Reference Member State (RMS), the Medicines and Healthcare products Regulatory Agency of the United Kingdom (MHRA) and the agreement of all the Concerned Member States (CMS) that Iluvien is approvable, Alimera Sciences, Inc. recently reported the positive outcome of the Decentralized Procedure (DCP) for Iluvien in Europe. The regulatory process will now enter the national phase of the DCP in which the RMS and each CMS grants its national license. Iluvien will be indicated for the treatment of vision impairment associated with chronic DME considered insufficiently responsive to available therapies. Read more here.
  • BIOPTIGEN CLEARED TO MARKET ENVISU SDOIS IN CANADA. Bioptigen Inc. has received a medical device license from Health Canada to begin marketing its hand-held Enisu SDOIS c2200 and C2300 ophthalmic imaging systems for patient use. The company's Envisu C series SDOIS imaging systems use low-power, near-infrared light to generate real-time, high-resolution, depth-resolved images of eye structures, equipping researchers and clinicians to explore new avenues of understanding in eye disease progression, detection and treatment. Availability of Envisu systems in the United States for patient use is dependent on review and market clearance by the FDA. Get additional information at www.bioptigen.com.
  • SANTEN TO LAUNCH NEW OTC EYE DROP IN JAPAN. On March 10, 2012, Santen Pharmaceutical Co., Ltd. will launch its new OTC eye drop, Sante Medical Guard, a sister product of Sante Medical 10, in Japan. The new product contains maximum therapeutic concentrations of flavin adenine dinucleotide sodium (active vitamin B2) to enhance corneal tissue regeneration and promote healing, and chondroitin sulfate sodium to moisturize and protect the cornea. Santen says Sante Medical Guard protects against serious eye conditions and provides relief for symptoms of eye inflammation such as soreness, pain and dry eye irritation. More information is available at www.santen.com.

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