Review of Ophthalmology Online

Volume 14, Number 17
Monday, April 23, 2018


In this issue: (click heading to view article)
######### Association of Increased Plasma TNF-α Levels With POAG
######### Accuracy and Precision of Anti-VEGF Agents in a Clinical Setting
######### OCTA Vessel Density Changes in Glaucomatous Eyes’ Macular Zones
######### Predicting AREDS Severity Scale for AMD from Color Fundus Photography


Association of Increased Plasma TNF-α Levels With POAG

Elevated levels of tumor necrosis factor alpha, a pro-inflammatory cytokine, can induce retinal ganglion cell death apoptosis and play a critical role in glaucomatous neurodegeneration, researchers wrote. Based on the possible role of inflammation and oxidative stress in the pathogenesis of primary open-angle glaucoma, they investigated the association between plasma levels of TNF-α in POAG compared with non-glaucomatous controls.

In a case-control retrospective cohort of 51 POAG cases and 88 controls, researchers measured plasma TNF-α levels using an enzyme-linked immunosorbent assay.

The mean TNF-α level was significantly elevated in POAG cases (1.88 ±2.17 pg/mL) compared with controls (0.93 ±1.49 pg/mL; p=0.003), and the overall dose-response trend was significant (Χ2=6.12, df=2; p=0.047). Researchers reported finding no statistical differences in age, gender or systemic disease distribution, although they found a modest negative and significant correlation between TNF-α level and number of anti-glaucoma medications—a clinical index of POAG severity. Moreover, logistic regression analysis showed that the risk of POAG was most significantly affected by TNF-α level and not by age and sex.

Researchers concluded that high systemic levels of the inflammatory cytokine TNF-α was associated with POAG, although they cautioned that its use as a potential biomarker for early glaucoma diagnosis and disease severity needs further investigation.

SOURCE: Kondkar AA, Sultan T, Almobarak FA, et al. Association of increased levels of plasma tumor necrosis factor alpha with primary open-angle glaucoma. Clin Opthalmol 2018; Apr 12. [Epub ahead of print].

Accuracy and Precision of Anti-VEGF Agents in Clinical Setting

Investigators evaluated the accuracy and precision of anti-vascular endothelial growth factor volume delivery by intravitreal injections in the clinical setting. They measured volume output in 669 injections administered to individuals, calculated from the difference in syringe weight before and after expelling the drug.

Three groups were included: prefilled bevacizumab 1 mL syringe (group 1, n=432); pre-filled ranibizumab in a small-volume syringe with low dead-space plunger design (group 2, n=125); and aflibercept drawn and injected using a 1-mL syringe (group 3, n=112). Investigators analyzed accuracy using mean absolute percentage error and precision by coefficient of variation.

Volume outputs in all three groups were significantly different from the target of 50 μL (p<0.0001 for all), and mean absolute percentage error values were 12.25 ±5.92 percent in group 1, 13.60 ±8.75 percent in group 2 and 24.69 ±14.84 percent in group 3. No difference was found between groups 1 and 2, but both were significantly more accurate than group 3 (p<0.0001 for both).

Investigators wrote that current delivery practices for intravitreal injections are highly variable, with overdelivery of the anti-VEGF drugs measured in most cases and underdelivery in 16.3 percent of injections. They added that use of a prefilled syringe was associated with improved accuracy and that low dead-space plunger design may improve precision.


SOURCE: Loewenstein I, Goldstein M, Moisseiev J, et al. Accuracy and precision of intravitreal injections of anti-vascular endothelial growth factor agents in real life: What is actually in the syringe? Retina 2018; Apr 13. [Epub ahead of print].

OCTA Vessel Density Changes in Glaucomatous Eyes’ Macular Zones

Scientists evaluated whether macular optical coherence tomography angiography could detect altered vessel density in the superficial and deep vascular plexus in glaucomatous eyes, and assessed the diagnostic utility of individual VD parameters. One of the researchers has lectured on behalf of OptoVue, maker of the AngioVue OCTA device.

The macular VDs of 135 eyes—85 diagnosed with glaucoma and 50 healthy controls—were examined using two OCTA devices (the AngioVue and Zeiss Meditec’s AngioPlex). No study participants had vascular pathology, diabetes or vasoactive medication. Scientists measured the macular VD at two different levels of segmentation—superficial (SL) and deep (DL) retinal vascular plexus—with a 6 × 6-mm macula scan, and correlated VD with various structural and functional measurements. To test the accuracy of differentiation between eyes with and without glaucoma, scientists calculated the ROC curve and the AUC.

Macular VDs were significantly lower in SL and DL in glaucomatous eyes than in healthy eyes (p=SL<0.0001; DL=0.009). Scientists found no significant differences in VD between the SL and DL (p=6.60; 10 to 18) and determined the greatest reduction of VD to be in glaucomatous eyes in the inferior macular sector. Scientists found no correlation of VD with age or refractive error, but did find moderate to high correlation with intraocular pressure, time of initial diagnosis, mean deviation, ganglion cell complex, peripapillary retinal nerve fiber layer thickness, cup-to-disc ratio and rim area. Among the 14 individual features of macular VD, whole VD in the SL had the best diagnostic accuracy (77.6 percent) as measured by the area under the ROC.

Scientists reported that OCTA helped to pinpoint glaucomatous damage through measurements of the macular VD in the SL and DL, and suggested this strategy could be an additional diagnostic tool to detect glaucoma independently of the optic nerve.

Source: Lommatzsch C, Rothaus K, Koch JM, et al. OCTA vessel density changes in the macular zone in glaucomatous eyes. Graefes Arch Clin Exp Ophthalmol 2018; Apr 10. [Epub ahead of print].

Predicting AREDS Severity Scale for AMD from Color Fundus Photography

While classification of age-related macular degeneration disease stage is essential to understanding risk and progression, several systems based on color fundus photographs require in-depth and time-consuming analysis of fundus images, researchers wrote. As such, they evaluated an automated computer-based classification algorithm to assess AMD risk and progression based on a large collection of color fundus images, as part of a cross-sectional, population-based study.

A total of 120,656 manually graded color fundus images from 3,654 Age-related Eye Disease Study participants >55 years of age without non-AMD sight-threatening diseases were enrolled. Researchers evaluated the performance of the algorithm in 5,555 fundus images from the population-based Kooperative Gesundheitsforschung (Augsburg, Germany) study.

They defined 13 classes (nine AREDS steps, three late AMD stages and one for ungradable images) and trained several convolution deep-learning architectures. An ensemble of network architectures improved prediction accuracy, and an independent dataset aided in determining the algorithm’s performance. The main outcome measures included κ statistics—which measure inter-rater agreement for qualitative (categorical) items—and accuracy to evaluate the concordance between predicted and expert human grader classification.

A network of six neural net architectures predicted the 13 classes in the AREDS test set with a quadratic weighted κ of 92 percent (CI, 89 to 92 percent) and an overall accuracy of 63.3 percent. In the independent dataset, images wrongly classified as AMD were mainly the result of a macular reflex observed in young individuals. By restricting the analysis to individuals >55 years of age and excluding other prior retinopathies, the weighted κ increased to 50 percent, and the unweighted κ increased to 63 percent. The algorithm detected 84.2 percent of all fundus images with signs of early or late AMD; overall, 94.3 percent of healthy fundus images were classified correctly.

Researchers determined that the deep-learning algorithm revealed a weighted κ outperforming human graders in the AREDS study and was suitable to classify AMD fundus images in other datasets using individuals >55 years of age.

SOURCE: Grassmann F, Mengelkamp J, Brandl C, et al. A deep learning algorithm for prediction of age-related eye disease study severity scale for age-related macular degeneration from color fundus photography. Ophthalmology 2018; Apr 10. [Epub ahead of print].

  • Glaukos iStent Trial Results: Reduction in Unmedicated IOP in Glaucoma Subjects Undergoing Cataract Surgery
    Glaukos announced that its two-year U.S. Investigational Device Exemption trial data showed that the iStent inject Trabecular Micro-Bypass System achieved a statistically significant reduction in unmedicated diurnal intraocular pressure in individuals undergoing cataract surgery. In the prospective, randomized, multicenter clinical trial, 387 subjects were randomized to iStent inject in combination with cataract surgery, and 118 subjects were randomized to cataract surgery only. The iStent inject met the study’s primary and secondary effectiveness endpoints: At 24 months, 75.3 percent of the iStent inject cohort achieved a 20 percent or greater reduction in unmedicated IOP compared with 61.9 percent for the cataract-only cohort; and at 24 months, the mean unmedicated IOP reduction was 6.9 mmHg for the iStent inject cohort compared with 5.4 mmHg for the cataract-only cohort. Read more.

  • EyePoint Issued Two Notices of Allowances for DEXYCU-related Patents
    EyePoint Pharmaceuticals announced that the U.S. Patent and Trademark issued Notices of Allowance for two patents covering DEXYCU, the company's FDA-approved long-acting intraocular extended-release dexamethasone suspension injection for the treatment of postoperative inflammation. The first patent includes claims relating to a method of treating inflammation of an eye following cataract surgery by delivering extremely small (4 µL to 6 µL) amounts of dexamethasone in triethyl acetyl citrate. The second includes claims relating to loading and delivering a small-dose volume from an injection syringe. Once issued, this patent will expire in 2032. Read more.

  • Alcon Products Get Upgrades
    Alcon recently announced modifications to two of its flagship products. In mid-April, Alcon introduced the CyPass Ultra System, which it says will streamline the process of loading the CyPass Micro-Stent glaucoma device. The CyPass Ultra System now comes pre-loaded with the micro-stent, rather than requiring a technician to load it at the time of the procedure. The other changes came to Alcon’s LenSx femtosecond laser. The LenSx is now indicated for two new, 510(k)-approved uses: creating tunnels for intracorneal ring segments; and corneal pockets for presbyopia-correcting inlays like the Kamra. Link to CyPass news. Link to LenSx information.

  • FDA Approves Lensar Laser for Corneal Pockets and Flaps
    Lensar recently announced that its device, the LENSAR Laser System with Streamline IV, received 510(k) clearance from the FDA to include the creation of the corneal pockets and flaps used in ophthalmic procedures treating presbyopia such as the Kamra intracorneal inlay. Read more.

  • Visumax Expands Functionality
    Zeiss announced that its Visumax femtosecond laser received 510(k) clearance from the FDA to create intracorneal tunnels. Zeiss says the new feature will allow surgeons to create versatile incisions for the implantation of intracorneal rings. Read more.

  • Allergan Launches TrueTear Intranasal Neurostimulation Device During ASCRS Annual Meeting
    Allergan announced the official launch of TrueTear, the first and only FDA-cleared device developed to temporarily increase tear production during neurostimulation in adult patients, at the 2018 American Society of Cataract and Refractive Surgery meeting in Washington, D.C. in mid-April. The handheld neurostimulation device with disposable tips is inserted into the nasal cavity to induce the production of natural tears. In two clinical trials, the device was shown to be safe and effective for temporarily increasing tear production in adult patients. Read more.

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