Review of Ophthalmology Online

Volume 14, Number 13
Monday, March 26, 2018


In this issue: (click heading to view article)
######### Aqueous Humor Cytokine Levels & Intravitreal Ranibizumab in DME
######### Distribution & Progression of VF Defects with Binocular Vision in Glaucoma
######### Conbercept for Treatment-naive nAMD
######### Role of Corneal Hysteresis in Evaluating Possible NTG


Aqueous Humor Cytokine Levels & Intravitreal Ranibizumab in DME

Researchers wrote that variability in response to anti-vascular endothelial growth factor treatment in diabetic macular edema remains a significant clinical challenge and that biomarkers could help anticipate responses to anti-VEGF therapy. As such, researchers analyzed aqueous humor cytokine level changes in response to intravitreal ranibizumab therapy for the management of DME, and determined the association between baseline aqueous levels and anatomic response.

As part of a prospective, multicenter cohort study, they recruited from December 22, 2011, to June 13, 2013, 49 participants with diabetes mellitus complicated by center-involving DME, with a central subfield thickness of 310 μm or greater (as revealed on spectral-domain optical coherence tomography), and performed statistical analyses from March 1, 2017, to June 1, 2017. A total of 48 participants proceeded to follow-up.

Participants received monthly injections of ranibizumab (0.5 mg) for three months. Aqueous fluid for cytokine analysis was obtained at baseline and at the two-month visit, and researchers carried out multiplex immunoassays in duplicate for:
• placental growth factor;
• transforming growth factor beta 2;
• intercellular adhesion molecule 1;
• interleukin 6;
• IL-8;
• IL-10;
• vascular intercellular adhesion molecule; and
• monocyte chemoattractant protein 1.

Main outcomes and measures included baseline and two-month changes in aqueous cytokine levels, three-month changes in SD-OCT central subfield thickness and macular volume, and the statistical association between baseline aqueous cytokine levels and measures of anatomic response to ranibizumab in center-involving DME.

Among the 48 participants, the mean (SD) age was 61.9 (7.1) years; 36 participants (75 percent) were men. The following cytokines were lower at month two vs. baseline:
• ICAM-1 (median change, -190.88; interquartile range, -634.20 to -26.54; p<0.001);
• VEGF (median change, -639.45; IQR, -1,040.61 to -502.61; p<0.001);
• placental growth factor (median change, -1.31; IQR, -5.99 to -0.01; p<0.001);
• IL-6 (median change, -38.61; IQR, -166.72 to -2.80; p<0.001); and
• monocyte chemoattractant protein 1 (median change, -90.13; IQR, -382.74 to 109.47; p=0.01).
When controlling for age, foveal avascular zone size and severity of retinopathy, multiple linear regression determined that increasing baseline aqueous ICAM-1 was associated with a favorable anatomic response in terms of reduced SD-OCT MV at three months (every additional 100 pg/mL of baseline ICAM-1 was associated with a reduction of 0.0379 mm3; p=0.01). Conversely, increasing baseline aqueous VEGF was associated with a less favorable SD-OCT MV response at three months (every additional 100 pg/mL of baseline VEGF was associated with an increase of 0.0731 mm3; p=0.02) and was associated with lower odds of being a central subfield thickness responder (OR, 0.868; CI, 0.755-0.998).

Researchers determined that elevated aqueous ICAM-1 and reduced VEGF levels at baseline were associated with a favorable anatomic response to ranibizumab in DME, although the findings didn’t always reveal a direct correlation between anatomic and visual acuity response.

SOURCE Hillier RJ, Ojaimi E, Wong DT, et al. Aqueous humor cytokine levels and anatomic response to intravitreal ranibizumab in diabetic macular edema. JAMA Ophthalmol 2018; Mar 8.[Epub ahead of print].

Distribution & Progression of VF Defects with Binocular Vision in Glaucoma

Investigators evaluated the distribution and progression of glaucomatous visual field defects with binocular vision. They included 167 individuals (average age, 67 ±10.7 y) with glaucoma who received the Humphrey 24-2 VF test (SITA-Standard) for the two eyes.

Using the Best Location algorithm, they calculated subjects’ integrated binocular VF from their Humphrey 24-2 results. Of 167 subjects, 77 (average age, 68 ±11 y) also underwent monocular/binocular Humphrey Esterman tests. Investigators classified stages of glaucomatous VF loss by the Esterman Disability Score for each test, and evaluated the distribution and progression of defects with binocular vision for each stage. They also investigated frequencies of the defects in the upper and lower halves of the VF.

With the integrated binocular VF, glaucomatous VF defects were most frequently found around Mariotte blind spots and Bjerrum areas, extending to the periphery. With the binocular Humphrey Esterman VF, defects were most frequently found around bitemporal and Bjerrum areas. In subjects with the earliest glaucoma, integrated binocular VF results showed 31 percent had defects in the upper fields, 49 percent had defects in the lower fields and 20 percent had defects in both halves of the VF.

Investigators frequently found glaucomatous VF defects with binocular vision at the Mariotte blind spots in the central VFs and around the bitemporal areas in the periphery, which they wrote appeared to have distributions and progression different from those of the defects previously reported with monocular vision.


SOURCE: Hashimoto S, Matsumoto C, Eura M, et al. Distribution and progression of visual field defects with binocular vision in glaucoma. J Glaucoma 2018; Mar 19. [Epub ahead of print].

Conbercept for Treatment-naive nAMD

Scientists assessed the efficacy and safety of intravitreal conbercept in individuals with treatment-naive neovascular age-related macular degeneration in a real-life setting in China.

The study involved three consecutive intravitreal injections of conbercept following a pro re nata protocol. The main outcomes were changes in Early Treatment Diabetic Retinopathy Study best-corrected visual acuity and central retinal thickness between the baseline and month 12.

Mean BCVA improved from 39.39 ±24.91 letters at baseline to 44.26 ±22.89 letters at the final follow-up (p<0.001). At month 12, the proportion of optimal responses was 43.48 percent compared with 36.96 percent of poor responses and 19.56 percent of nonresponses. A mean central retinal thickness of 480.94 ±178.47 μm at baseline was significantly reduced to 366.33 ±173.52 μm at month 12. Subjects received a median of 5.32 intravitreal injections. At month 12, scientists found that the mean change in BCVA of eyes with intraretinal cystoid fluid at baseline was markedly lower than that of eyes without intraretinal cystoid fluid. No adverse events were attributed to conbercept.

Scientists wrote that, at the 12-month follow-up, conbercept was shown to be a safe and effective treatment for individuals with treatment-naive nAMD in a real-life setting.

Source: Li X, Luo H, Zuo C, et al. Conbercept in patients with treatment-naive neovascular age-related macular degeneration in real-life setting in China. Retina. 2018 Mar 15.

Role of Corneal Hysteresis in Evaluating Possible NTG

A number of studies report the role of corneal hysteresis as an independent risk factor for the diagnosis and risk of progression of normal-tension glaucoma. As such, researchers measured CH with the Ocular Response Analyzer in individuals with intraocular pressure <21 mmHg to investigate if a low CH would identify NTG in an Asian-based practice, as part of a prospective, cross-sectional study of individuals who underwent routine eye exams during 2016 in a private practice in Honolulu.

Inclusion criteria were:
• ≥65 years;
• IOP <21 (compensated IOP by ORA); and
• CH values <10 using ORA as measured by a single experienced technician. Exclusion criteria were:
• sight-limiting ocular or corneal disease that would preclude accurate measurements for the purposes of the study;
• any individual who had difficulty in being tested with the ORA; and
• individuals who had any history of any type of glaucoma.

All individuals who met the inclusion criteria underwent fundus photography to measure cup-to-disc ratio and cup-to-disc asymmetry, and had central corneal thickness measured. Researchers used ocular coherence tomography to measure thickness of the retinal nerve fiber layer. They classified eyes with an average RNFL thickness of less than 80 µm as possible NTG, and scheduled them for a visual field test. The field exam was considered valid only if fixation, false positives and false negatives were within the acceptable range. Researchers collected subject demographics and data on preexisting disease, including age, sex, coexisting medical conditions and previous intraocular surgery. Individuals with RNFL thinning on OCT had a Humphrey VF test to confirm the glaucoma diagnosis. A total of 76 eyes of 46 individuals that met the eligibility criteria were included, while 21 previously undiagnosed eyes were confirmed as having NTG, corresponding with an incidence of 27.6 percent.

Researchers concluded that CH was a valuable measurement to assist in early diagnosis of NTG.

SOURCE: Chen M, Kueny L, Schwartz AL. The role of corneal hysteresis during the evaluation of patients with possible normal-tension glaucoma. Clin Ophthalmol 2018 2018:12;555-9.

  • FDA Approves Genentech’s Lucentis (Ranibizumab Injection) 0.3 Mg Prefilled Syringe for DME & DR
    Genentech announced that the U.S. Food and Drug Administration approved the Lucentis (ranibizumab injection) 0.3 mg prefilled syringe as a new method of administering the medicine to treat all forms of diabetic retinopathy. The Lucentis 0.3 mg PFS is the first syringe prefilled with an anti-vascular endothelial growth factor agent FDA-approved to treat both diabetic retinopathy and DME. Genentech says the device—which is made of borosilicate glass and packaged in a single-use sterile, sealed tray—enables physicians to eliminate several steps in the preparation and administration process. The device, expected to be available in the second quarter of 2018, is indicated for the treatment of neovascular age-related macular degeneration, macular edema following retinal vein occlusion and myopic choroidal neovascularization. In April 2017, Lucentis 0.3 mg became the first FDA-approved medicine to treat all forms of diabetic retinopathy in people with or without diabetic macular edema. Read more.

  • B+L Introduces 25- & 27-gauge Vitrectomy Cutters for Stellaris Elite Vision
    Bausch + Lomb introduced 25- and 27-gauge Bi-Blade dual port vitrectomy cutters for its Stellaris Elite vision enhancement system. The new probes will be featured at the Vit-Buckle Society Meeting in Miami Beach, Fla., during a live surgery on March 23, and available for trial during the Vit-Buckle Society Wet Lab on March 24. B+L says that while single-port cutters cut only in the forward direction, Bi-Blade cutters cut in forward and backward directions, enabling two cuts per cycle. This design, used with the Stellaris Elite, offers a rate of 15,000 cuts per minute for increased flow efficiency and control compared with guillotine cutters. The company says it also allows for more consistent flow rate and reduced retinal traction. Read more.

  • pSivida Gets FDA NDA Nod for Durasert Treatment for Posterior Segment Uveitis
    pSivida’s New Drug Application for three-year Durasert treatment for posterior segment uveitis was accepted by the U.S. Food and Drug Administration for filing, and has a Prescription Drug User Fee Act date of Nov. 5, 2018. The NDA includes data from two Phase III studies that achieved primary efficacy endpoints at six months with a p-value <0.001. In addition, the safety profile in individuals treated with Durasert for posterior segment uveitis was consistent with the safety profile of steroid treatments considered standard care. Read more.

  • Avedro Announces FDA Agreement for Phase III Trial of Epi-on Cross-linking Treatment
    Avedro reached an agreement with the U.S. Food and Drug Administration regarding a Special Protocol Assessment on the design of a Phase III clinical trial for an epithelium-on corneal collagen cross-linking procedure to treat individuals with progressive keratoconus. The agreement stipulates that the Phase III clinical trial design—which includes clinical endpoints, trial population and statistical analyses—adequately address objectives that, if met, would form the primary basis of a regulatory submission for FDA approval of the company’s epi-on cross-linking treatment. The multicenter, randomized, controlled study is comparing a novel, accelerated corneal collagen cross-linking procedure, including the use of oxygen, with a control in approximately 275 subjects with progressive keratoconus. Read more.

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