Review of Ophthalmology Online

FROM THE EDITORS OF REVIEW OF OPHTHALMOLOGY:







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Volume 18, Number 37
Monday, September 10, 2018
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SEPTEMBER IS HEALTHY AGING MONTH



In this issue: (click heading to view article)
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######### CH as a Risk Factor for Predicting Glaucoma Development
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######### Complement Levels in Vitreous Aspirates of PDR & RD Eyes
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######### Long-term Changes in Ocular Surface Post-trabeculectomy
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######### VA Outcomes Based on Initial Treatment Response in nAMD
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  Briefly

 

CH as a Risk Factor for Predicting Glaucoma Development

Researchers assessed the role of corneal hysteresis as a risk factor for development of glaucoma, as part of a prospective, observational cohort study. They followed 287 eyes of 199 individuals suspected of having glaucoma for an average of 3.9 ±1.8 years.

All eyes had normal visual fields at baseline. Development of glaucoma was defined as occurrence of three consecutive abnormal standard automated perimetry tests during follow-up, i.e., pattern standard deviation <5 percent, and/or Glaucoma Hemifield Test outside normal limits. Measurements of CH were acquired at baseline using the Ocular Response Analyzer. Researchers used univariable and multivariable Cox regression models to investigate baseline factors associated with development of VF loss over time.

Fifty-four (19 percent) eyes developed repeatable VF defects during follow-up. CH measurements at baseline were significantly lower in individuals who developed glaucoma (9.5 ±1.5 mmHg) vs. those who didn’t (9.5 ±1.5 mmHg) (p=0.012). Each 1 mmHg lower CH was associated with a 21-percent increase in the risk of developing glaucoma during follow-up (CI, 1.04 to 1.41; p=0.013). In a multivariable model adjusting for age, intraocular pressure, central corneal thickness, PSD and treatment, CH was still predictive of glaucoma development (HR=1.20; CI, 1.01 to 1.42; p=0.040).

Researchers found that baseline lower CH measurements were significantly associated with increased risk of developing glaucomatous VF defects over time. They wrote that these findings supported the role of CH as a risk factor for developing glaucoma.

SOURCE: Susanna CN, Diniz-Filho A, Daga FB, et al. A prospective longitudinal study to investigate corneal hysteresis as a risk factor for predicting development of glaucoma. Am J Ophthalmol 2018;187:148-52.





Complement Levels in Vitreous Aspirates of PDR & RD Eyes

Investigators evaluated levels of complement factors in the vitreous of human eyes with retinal detachments and proliferative diabetic retinopathy. Samples were collected from eyes undergoing routine vitrectomy at the University of Colorado Health Eye Center in Aurora.

Investigators measured complement factor D, component C5/C5a and component C9 levels using enzyme-linked immunosorbent assay and multiplex assays. They compared eyes with retinal detachment and PDR to controls consisting of eyes with macular holes or epiretinal membranes.

Levels of complement factor D in PDR (mean=2,110 ng/mL, p=0.001) and RD (mean=660.9 ng/mL, p=0.03) eyes were statistically significantly higher than those of controls (mean=290.5 ng/mL). Levels of complement component C9 were also more elevated in PDR eyes (p=0.004) compared with controls, though not in RD eyes.

Investigators concluded that elevated complement factors, particularly of the alternative pathway, were noted in PDR and RD eyes compared with controls. They suggested that oxidative stress in RD and PDR eyes might have led to complement dysregulation and alternative complement upregulation.

SOURCE: Manoharan N, Patnaik JL, Olson JL, et al. Increased complement levels in human vitreous aspirates of proliferative diabetic retinopathy and retinal detachment eyes. Retina 2018; Aug. 24. [Epub ahead of print].



Long-term Changes in the Ocular Surface Post-trabeculectomy

Scientists evaluated changes in the ocular surface of individuals post-trabeculectomy, in addition to associations with conjunctival inflammatory gene expression, as part of a single-arm, interventional cohort study performed at a tertiary referral center.

They recruited 33 predominantly male participants ages 66.88 ±9.76 at baseline. And they assessed dry-eye symptom questionnaires, tear osmolarity, Schirmer's tests, noninvasive tear breakup times, conjunctival redness and corneal fluorescein staining results. They performed conjunctival impressions using the Eyeprim device and, after RNA extraction, analyzed transcripts of 255 inflammatory genes using the Nanostring nCounter assay.

Scientists noted significant decreases in inferior corneal staining at six months (p<0.05)(n=22) and tear osmolarity at 12 months (p<0.01)(n=27). No individuals required glaucoma eyedrops post-surgery up to three years. At baseline, 31/33 transcript profiles passed quality control, and after normalization scientists analyzed 249 transcripts. They recorded the following findings:

• Increased discomfort was associated with higher levels of the protein tyrosine kinase 2 at the cross-sectional analysis at baseline.
• Lower baseline complement factor D levels and higher levels of Mitogen associated kinase 8, MAP3K1 and MyD88 were associated with the presence of corneal staining at six months.
• Nine genes, including the proinflammatory lipo-oxygenase, showed a significantly reduced level at three years (n=5).

Scientists reported that glaucoma surgery (if anti-glaucoma eyedrops were no longer necessary) might confer long-term benefits to the ocular surface due to reduced expression of conjunctival pro-inflammatory and immune-related genes.

SOURCE: Tong L, Hou AH, Wong TT, et al. Altered expression level of inflammation-related genes and long-term changes in ocular surface after trabeculectomy, a prospective cohort study. Ocul Surf 2018; Jun 21. [Epub ahead of print].




Acuity Outcomes Based on Initial Treatment Response in nAMD

Researchers explored various methods to assess the early response to vascular endothelial growth factor inhibitors for neovascular age-related macular degeneration, and investigated associations with three-year visual acuity outcomes, as part of an observational study.

The study included 2,051 treatment-naïve eyes from 1,828 individuals in the Fight Retinal Blindness! outcomes registry receiving anti-VEGF therapy between Jan. 1 2007, and March 1, 2014, and specifically injections within the first three months.

Researchers defined early response as occurring until the fourth injection. They analyzed various early response metrics, including continuous and categorical variables such as:
• good VA (≥70 letters [20/40]);
• absolute change in VA from baseline;
• inactivity during time to first grading of the choroidal neovascular lesion; and
• maximum rate of VA change between successive injections.
Main outcome measures included the proportion of eyes achieving ≥70 letters at three years.

Achieving good vision at three years was significantly associated with:
• having good vision by the fourth injection (OR [CI]: 9.8 [6.5, 14.7] for VA ≥70 vs. VA <70 letters);
• small (1 to 5 letters) or large (>5 letters) early VA gains (1.8 [1.2, 2.6], p=0.002 and 1.8 [1.3, 2.5], p<0.001 vs. eyes with early VA loss);
• fewer injections until grading of lesion inactivity (1.6 [1.2, 2.1], p<0.001 for ≤3 vs. >3 injections); and
• gradual change (between -4 and 4 letters) or rapid (>5 letters) gains between successive injections (1.7 [1.1, 2.6], p=0.015 and 1.6 [1.1, 2.3], p=0.018 for gradual change and rapid gain vs. rapid loss).
• Eyes that achieved small or large early gains (65 letters) achieved similar vision at three years (64.7 letters), and had better vision than eyes with early VA loss (57.2 letters).

Attainment of good vision by the fourth injection was strongly associated with three-year visual outcomes, while other early response parameters had a moderate association. Researchers determined that the early response during the initial three monthly loading doses could be a useful guide for subsequent treatment decisions.

SOURCE: Nguyen V, Daien V, Guymer R, et al. Projection of long-term visual acuity outcomes based on initial treatment response in neovascular age-related macular degeneration. Ophthalmology 2018; Aug 24. [Epub ahead of print].






  • Alcon Voluntarily Withdraws Cypass Micro-Stent from Global Market
    Alcon announced an immediate, voluntary market withdrawal of the CyPass Micro-Stent from the global market. In addition, Alcon advised surgeons to cease further implantation with the CyPass Micro-Stent and return unused devices to the company. This decision and corresponding recommendation is based on an analysis of five-year post-surgical data from the COMPASS-XT long-term safety study. The U.S. FDA approved the CyPass Micro-Stent in July 2016 for use in conjunction with cataract surgery in adult patients with mild-to-moderate primary open-angle glaucoma, based on the results demonstrating a statistically significant reduction in intraocular pressure at two years post-surgery in subjects implanted with the stent at the time of cataract surgery compared with subjects undergoing cataract surgery alone. At five years, however, the CyPass Micro-Stent group experienced statistically significant endothelial cell loss compared with the group who underwent cataract surgery alone. Read more.


  • EyeGate EGP-437 in Anterior Uveitis Shows Clinical Efficacy But Not Non-inferiority to Controls
    EyeGate Pharmaceuticals announced mixed topline results from its Phase III study evaluating the safety and efficacy of EGP-437 delivered through the EyeGate II Drug Delivery System in individuals with noninfectious anterior segment uveitis. Although EGP-437 showed clinical efficacy, defined as a reduction in anterior chamber cell score throughout the study, EyeGate reports that it didn’t demonstrate non-inferiority to the prednisolone acetate ophthalmic solution control group. This was measured as the proportion of subjects with an anterior cell count of zero (a sign of diminished inflammation) at day 14. EyeGate says it plans to review the data and assess its strategic options for EGP-437 going forward. Read more.


  • Phase III Results of a New Steroid Formulation
    Bausch + Lomb recently announced the results of its Phase III, multicenter, double-masked, vehicle-controlled, randomized, parallel-group study of submicron loteprednol etabonate ophthalmic gel, 0.38%. Submicron LE ophthalmic gel, 0.38% has a reduced concentration and reduced dosing frequency versus existing formulations of loteprednol etabonate, the company says. In the study, this investigational formulation of the drug met both of the primary efficacy endpoints in that it was significantly more effective than vehicle in completely resolving ocular inflammation and pain following cataract surgery. Additionally, the results showed that the drug had an acceptable safety profile regardless of whether it was administered two or three times per day. A pre-publication article with results of the study were published online in the Journal of Cataract and Refractive Surgery. Read more.



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