Volume 18, Number 2
THE LATEST PUBLISHED RESEARCH
Welcome to Review of Ophthalmology's Retina Online newsletter. Each month, Medical Editor Philip Rosenfeld, MD, PhD, and our editors provide you with this timely and easily accessible report to keep you up to date on important information affecting the care of patients with vitreoretinal disease.
INSIDE THIS ISSUE:
A T&E vs. PRN Regimen in nAMD: IDEM Study
Researchers reported the 24-month outcomes of a pro re nata compared with a treat and extend regimen in patients previously treated for neovascular age-related macular degeneration, as part of a two-year prospective single-center study.
Previously treated patients for nAMD were randomized to treatment with a T&E or PRN protocol. The main outcome measured was change in best-corrected visual acuity from baseline to month 24. Secondary outcomes encompassed anatomical features such as central retinal thickness, number of intravitreal injections (IVI) and visits required.
Here are some of the findings:
Researchers reported a statistically validated noninferiority between the PRN and T&E regimens in terms of visual and anatomical outcomes at 24 months, with significantly more IVI administered in the T&E regimen.
SOURCE: Faudi E, Gauthier AS, Delbosc B, et al. To investigate treat and extend versus pro re nata regimen in neovascular age-related macular degeneration: Results from the IDEM study. Graefes Arch Clin Exp Ophthalmol 2022; Jan 12. [Epub ahead of print].
Effects of Suspension of Anti-VEGF Treatment for nAMD in Clinical Setting
Researchers evaluated the outcomes of a suspension of anti-vascular endothelial growth factor treatments in eyes with neovascular age-related macular degeneration.
This retrospective study examined eyes having no exudation for 48 weeks while undergoing intravitreal anti-VEGF injections every 12 to 16 weeks. The rate and time of recurrences, best-corrected visual acuity, central subfield thickness (CST), number of visits and reactivity to anti-VEGF were determined after the suspension of the anti-VEGF treatments.
Here are some of the findings:
Researchers wrote that, although one-half of eyes had a recurrence within 24 months after a suspension of anti-VEGF treatment, BCVA was maintained after a resumption of the anti-VEGF treatments. However, they added, the number of hospital visits increased regardless of the recurrences, and the lesion stability was altered by the anti-VEGF suspension. As such, they suggested that clinicians explain the advantages and disadvantages of anti-VEGF suspension to nAMD patients.
SOURCE: Matsubara H, Matsui Y, Miyata R, et al. Effects of suspension of anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration in clinical setting. Graefes Arch Clin Exp Ophthalmol 2022; Jan 30. [Epub ahead of print].
Using SS-OCTA to Predict RPE Tear Development After nAMD Treatment
Scientists aimed to predict retinal pigment epithelium tear development after treatment for neovascular age-related macular degeneration using swept-source optical coherence tomography angiography.
This prospective study included 152 treatment-naïve eyes with neovascular AMD without high myopia that were followed up for one year after treatment. Eligible eyes were classified into eyes with or without RPE tear development. They were matched in a 1:2 ratio. The areas of choroidal neovascularization and RPE detachment (PED) were measured from OCTA and OCT en-face images, respectively. The OCTA-specific parameters representing CNV status were analyzed.
Here are some of the findings:
Researchers wrote that neovascular AMD with pre-treatment broad PED, high PED and small CNV area relative to the PED area had a high risk of RPE tear development after therapy although CNV status may not have an association.
SOURCE: Yasuhara S, Miyata M, Ooto S, et al. Predictors of retinal pigment epithelium tear development after treatment for neovascular age-related macular degeneration using swept-source optical coherence tomography angiography. Retina 2022; Jan 28. [Epub ahead of print].
Choriocapillaris/Sattler and Haller Layer Changes After Intravitreal Injection in nAMD Eyes
Investigators evaluated changes in choriocapillaris (CC)/Sattler and Haller layer thickness in eyes with neovascular age-related macular degeneration after aflibercept or ranibizumab injections.
The retrospective study included 70 eyes of 70 patients with treatment-naïve exudative nAMD treated with three consecutive injections of aflibercept (IVA) or ranibizumab (IVR). CC/Sattler and Haller layer thicknesses were measured at the nasal and temporal regions 1,000 µm from the center of the fovea by enhanced-depth imaging optical coherence tomography at baseline and after the three monthly intravitreal injections. In addition, the hyperfluorescence region (HF) was measured as the largest horizontal diameter of the hyperfluorescence area on the early-middle phase fluorescein angiographic images at baseline and after the three loading doses.
Here are some of the findings:
Investigators found that aflibercept treatment had a more pronounced effect on the CC/Sattler layer. They suggested that this finding may indicate that aflibercept treatment influences choroidal neovascularization, possibly by reducing the capillary permeability associated with active neovascularization in the CC layer.
SOURCE: Altunel O, Ozsaygili C. Assessment of choriocapillaris/Sattler and Haller layer changes after intravitreal injection in eyes with neovascular age-related macular degeneration: Aflibercept vs ranibizumab. Jpn J Ophthalmol 2022; Jan 4. [Epub ahead of print].
Local GA Growth Rates & Proximity to Non-exudative Type 1 MNV
Investigators analyzed the local growth rates of geographic atrophy adjacent to non-exudative type 1 macular neovascularization to determine if MNV influenced GA growth.
They followed eyes with GA and non-exudative type 1 MNV for at least one year. They imaged and measured GA and MNV using swept-source optical coherence tomography angiography scans. They computed Pearson correlations between local growth rates of GA (which were estimated using a biophysical GA growth model) and local distances-to-MNV. They computed corresponding p-values for the null hypothesis of no Pearson correlation using a Monte Carlo approach that adjusts for spatial autocorrelations.
Nine eyes were included in this study. Positive correlations (Pearson's r>0) were found between distance-to-MNV and local GA growth in eight (89 percent) of the eyes; however, in all but one eye (11 percent), correlations were relatively weak and statistically nonsignificant after Bonferroni correction (corrected p>0.05).
SS-OCTA imaging combined with GA growth modeling and spatial statistical analysis enabled quantitative assessment of correlations between local GA growth rates and local distances-to-MNV. Researchers wrote that the results weren’t consistent with non-exudative type 1 MNV having a strong inhibitory effect on local GA growth rates.
SOURCE: Trivizki O, Moult EM, Wang L, et al. Local geographic atrophy growth rates not influenced by close proximity to non-exudative type 1 macular neovascularization. Invest Ophthalmol Vis Sci 2022; Jan 3;63:1:20.
Diagnosing Persistent Hyper-transmission Defects on En Face OCT Images
Researchers studied the ability of graders to reliably identify precursor lesions to geographic atrophy, known as persistent choroidal hyper-transmission defects (hyperTDs), using en face optical coherence tomography images from eyes with non-exudative age-related macular degeneration.
The intergrader agreement study included 11 graders, who received formal training on how to identify persistent hyperTDs on en face OCT images. Persistent hyperTDs were defined as bright lesions having the greatest linear dimension (GLD) of at least 250 μm. Training consisted of a tutorial session followed by the grading of three pretest exercises, each consisting of three cases. After all graders scored 100 percent on the pretest exercises, they performed a final exercise consisting of 30 en face OCT images from 29 eyes with non-exudative AMD containing 107 hyperTDs that each grader needed to evaluate. The cases contained a variety of AMD-related atrophic lesions.
Main outcome measures included the sensitivity, positive predictive value (PPV) and modified accuracy for each grader.
A total of 1,177 hyperTDs from 30 en face OCT images were reviewed by the graders. Here are some of the findings:
Researchers reported that the accurate detection of persistent hyperTDs on en face OCT images by graders demonstrated the feasibility of using this OCT biomarker to identify disease progression in eyes with non-exudative AMD.
SOURCE: Liu J, Laiginhas R, Corvi F, et al. Diagnosing persistent hyper-transmission defects on en face OCT imaging of age-related macular degeneration. Ophthalmol Retina 2022; Jan 27. [Epub ahead of print].
Two Phase III Pivotal Trials of Brolucizumab for DME: KESTREL and KITE
Investigators compared the efficacy and safety of brolucizumab with aflibercept in patients with diabetic macular edema, as part of double-masked, 100-week, multicenter, active-controlled, randomized trials.
Subjects were randomized 1:1:1 to brolucizumab 3 mg/6 mg or aflibercept 2 mg in KESTREL (N=566) or 1:1 to brolucizumab 6 mg or aflibercept 2 mg in KITE (n=360). Brolucizumab groups received five loading doses every six weeks (q6w) followed by q12w dosing, with optional adjustment to q8w if disease activity was identified at predefined assessment visits; aflibercept groups received 5xq4w followed by fixed q8w dosing. The primary endpoint was best-corrected visual acuity change from baseline at week 52. Secondary endpoints included the proportion of subjects maintained on q12w dosing, change in DRSS score, and anatomical and safety outcomes.
Here are some of the findings:
Investigators found that brolucizumab 6 mg showed robust visual gains and anatomical improvements with an overall favorable benefit/risk profile in patients with DME.
SOURCE: Brown DM, Emanuelli A, Bandello F, et al. KESTREL and KITE: 52-week results from two Phase III pivotal trials of brolucizumab for diabetic macular edema. Am J Ophthalmol 2022; Jan 13. [Epub ahead of print].
Safety and Efficacy of Fluocinolone Acetonide Intravitreal Implant for DME: The PALADIN Study
Researchers assessed the long-term safety and efficacy of the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (Iluvien) in patients with diabetic macular edema, as part of a three-year, Phase IV, non-randomized, open-label observational study.
Participants included patients with DME who previously received corticosteroid treatment without a clinically significant rise in intraocular pressure (n=202 eyes in 159 patients; 36-month completers, n=94 eyes).
The prospective, observational study included patients who received a 0.19-mg FAc intravitreal implant at baseline and were then observed for safety-, visual-, anatomical- and treatment burden-related outcomes for up to 36 months.
Primary safety outcomes included changes in IOP and interventions to manage IOP elevations. Secondary outcomes included changes in best-corrected visual acuity, central subfield thickness and adjunctive DME treatment frequency
Here are some of the findings:
Researchers concluded that, in patients with DME, the 0.19-mg FAc implant provided improved visual outcomes and reduced treatment burden compared with previous treatments while maintaining a favorable safety profile.
SOURCE: Singer MA, Sheth V, Mansour SE, et al. Three-year safety and efficacy of the 0.19-mg fluocinolone acetonide intravitreal implant for diabetic macular edema: The PALADIN study. Ophthalmology 2022; Jan 18. [Epub ahead of print].
Associations Between Peripapillary RNFL and Choroidal Thickness with the Development and Progression of DR
Researchers evaluated the role of the peripapillary retinal nerve fiber layer (pRNFL) and peripapillary choroidal thickness (pCT) in the development and progression of diabetic retinopathy.
In the cohort study based on baseline and two-year follow-up data of the Guangzhou Diabetic Eye Study, patients with type 2 diabetes mellitus between the ages of 30 and 80 years were recruited from communities in Guangzhou. DR was graded by seven-field fundus photography after dilation of the pupil. pRNFL and pCT were measured via swept-source optical coherence tomography.
A total of 895 patients were included in the study. Here are some of the findings:
Researchers found that neurodegeneration shown by the thinning of pRNFL, and impaired choroidal circulation shown by the thinning of pCT were independently associated with DR onset. They added that assessing both metrics can improve the risk assessment for DR incidences.
SOURCE: Gong X, Wang W, Xiong K, et al. Associations between peripapillary retinal nerve fiber layer and choroidal thickness with the development and progression of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2022 Feb 1;63:2:7.
Combining Retinal and Choroidal Microvascular Metrics to Improve Discriminative Power for DR
Investigators used optical coherence tomography angiography parameters from the retinal and choroidal microvasculature to detect the presence and severity of diabetic retinopathy.
In this cross-sectional case-control study, OCTA parameters from the retinal vasculature, fovea avascular zone (FAZ) and choriocapillaris were evaluated from 3×3 mm2 fovea-centered scans. Areas under the receiver operating characteristic curve were used to compare the discriminative power on the presence of diabetes mellitus (DM), presence of DR and need for referral:
A total of 35 eyes from 27 participants with no DM and 132 eyes from 75 with DM were included. DR severity was classified into three groups: no DR group (62 eyes), NPDR (51 eyes) and PDR (19 eyes). Here are some of the findings:
Investigators reported that evaluating OCTA parameters from both the retinal and choroidal microvasculature in 3×3 mm scans improved the discrimination of DM and early DR.
SOURCE: Tan B, Lim NA, Tan R, et al. Combining retinal and choroidal microvascular metrics improves discriminative power for diabetic retinopathy. Br J Ophthalmol 2022; Feb 9. [Epub ahead of print].
Role of OCTA in Detecting and Monitoring Inflammatory CNV
Investigators evaluated the utility of optical coherence tomography angiography for the detection of inflammatory choroidal neovascularization (iCNV) and in monitoring response to treatment.
They retrospectively reviewed patients with a diagnosis of uveitis and associated iCNV with active exudation. Active iCNV was determined by spectral domain-OCT and/or fluorescein angiogram, and SD-OCTA outer retina to choriocapillaris (ORCC) slabs were evaluated for the presence of iCNV. Follow-up OCTA images were qualitatively assessed to determine if regression of iCNV occurred following treatment.
Thirteen eyes of 12 patients were included. Here are some of the findings:
Investigators concluded that OCTA was an effective modality for detecting iCNV and could provide detailed visualization regarding location, morphologic structure and flow of the iCNV as well as its response to therapy.
SOURCE: Kongwattananon W, Grasic D, Lin H, et al. The role of optical coherence tomography angiography in detecting and monitoring inflammatory choroidal neovascularization. Retina 2022; Jan 20. [Epub ahead of print].
Two-year Data for Vabysmo and Susvimo Released, FDA Approves Genentech’s Vabysmo for AMD & DME
Genentech released two-year outcomes of trials involving its drugs Vabysmo (formerly known only as faricimab) and Susvimo (formerly the Port Delivery System with ranibizumab).
In the studies, 60 percent of DME patients treated with Vabysmo could maintain vision while extending treatment interval to every four months at two years, compared to 50 percent at year one. Safety results were consistent across study arms, the company says, with no reported cases of retinal vasculitis or retinal occlusive events. Susvimo patients in the company's Archway wet AMD study treated every six months maintained vision and anatomic outcomes at the same level as patients who received monthly intravitreal ranibizumab injections over two years, Genentech says. In addition, 95 percent of patients treated every six months didn't need supplemental ranibizumab injections through each treatment interval. The company says Susvimo was generally well-tolerated, with a favorable benefit-risk profile. The most common adverse events (≥5 percent) were cataract, conjunctival bleb and vitreous hemorrhage. The data was presented and discussed at this year’s Angiogenesis, Exudation, and Degeneration 19th annual meeting (held virtually February 11 and 12). Learn more.
Regeneron Presents Phase II, Proof-of-Concept Results for High-dose Aflibercept
Regeneron Pharmaceuticals announced positive results through 44 weeks from its Phase II proof-of-concept trial evaluating an investigational 8 mg high dose of aflibercept compared to the currently-approved 2 mg dose of Eylea (aflibercept) injection in patients with wet age-related macular degeneration. The data was presented at the Angiogenesis (Angiogenesis, Exudation, and Degeneration) annual meeting on February 12. In new results, aflibercept 8 mg continued to show numeric improvements in anatomical and vision outcomes compared to the 2-mg dose of the drug through 44 weeks. Read more.
Opthea Announces OPT-302 Data in PCV
Opthea announced that findings on OPT-302 were presented at the annual Angiogenesis, Exudation, and Degeneration annual meeting, held virtually. The data focused on a prespecified subgroup analysis of a Phase IIb dose-ranging study of intravitreal OPT-302 in combination with ranibizumab, compared with ranibizumab alone, in participants with neovascular age-related macular degeneration. Sixty-six participants (18 percent) with PCV out of 366 patients were included. Eyes were randomized to receive a total of six intravitreal injections, once every four weeks, of ranibizumab (0.5 mg) plus OPT-302 (0.5 mg or 2 mg) or ranibizumab plus sham. The company says that OPT-302 combination therapy had a safety profile consistent with standard-of-care anti-VEGF-A monotherapy, and demonstrated greater improvements in best-corrected visual acuity and less retinal fluid compared to ranibizumab monotherapy. Read more.
EyePoint Announces Updated Interim Safety and Efficacy Data from Phase I DAVIO
SOURCE: EyePoint Pharmaceuticals, February 2022
Regenxbio Presents Interim Data from Phase II ALTITUDE Trial
Iveric Announces Positive Post Hoc Analysis from GATHER1
Iveric announced the positive results of a post hoc analysis that evaluated various geographic atrophy growth parameters to explore the rate of disease progression within various regions in the fovea in a subset of patients from the GATHER1 Zimura (avacincaptad pegol) Phase III clinical trial for the treatment of GA. The findings were consistent with the primary analysis results in the intent-to-treat population. Read more.
RPT Presents Clinical Data on Allogenic Bioengineered Cellular Implant in Advanced Dry AMD
Regenerative Patch Technologies (RPT) announced the publication of results in Stem Cell Reports from its Phase I/IIa clinical trial of the CPCB-RPE1 implant for advanced dry age-related macular degeneration. The bio-engineered scaffold supporting a layer of stem cell-derived retinal pigmented epithelial cells uses unmatched allogenic RPE cells as one of its two components. Subjects in the trial were legally blind in the treated eye at enrollment, and the implants were delivered to large areas of degenerative disease stemming from geographic atrophy. At an average of 34 months post-implantation, 27 percent (4/15) of patients showed more than seven letters of improvement in their best-corrected visual acuity, according to the company. Read more.
SOURCE: Regenerative Patch Technologies, February 2022
Nanoscope Expands Scientific Advisory Board Appointments, Announces FDA IND for MCO-010 Gene Therapy
Nanoscope Therapeutics expanded its Clinical and Scientific Advisory Board with the appointment of five new retinal experts. View the new members. Read more.
SOURCE: Nanoscope Therapeutics, February/January 2022
Last Patient Completes Treatment in Stealth’s Phase II GA Clinical Trial
Stealth BioTherapeutics announced the final patient in its ReCLAIM-2 Phase II trial for extra-foveal geographic atrophy associated with dry age-related macular degeneration completed treatment. The company is developing elamipretide for treatment of extra-foveal GA under FDA Fast Track designation. Read more.
Outlook Therapeutics to Submit FDA Biologics License Application
Outlook Therapeutics reported in a business update that it plans to submit a new FDA Biologics License Application in the first quarter of 2022 for ONS-5010 / Lytenava (bevacizumab-vikg), an investigational ophthalmic formulation of bevacizumab under development to be administered as an intravitreal injection for the treatment of wet age-related macular degeneration and other approved retinal diseases, now that its registration clinical trials are completed. Read more.
SOURCE: Outlook Therapeutics, January 2022
Kriya Licenses Gene Therapies for GA, Other Ocular Diseases
Kriya Therapeutics announced an exclusive agreement with the Medical University of South Carolina Foundation for Research Development to license next-generation complement-targeted gene therapies for the treatment of geographic atrophy and other ocular diseases. Through this agreement, Kriya is advancing therapies designed to express engineered molecules that selectively reduce complement hyperactivity following one-time administration. Read more.
SOURCE: Kriya Therapeutics, January 2022
UCI Researchers Reveal Molecular Mechanisms That Lead to Blindness
University of California, Irvine researchers in collaboration with the Max-Planck Institute of Biochemistry, have revealed, at a molecular level, key structural determinants of the highly specialized rod outer segment (ROS) membrane architecture of the eye, which is instrumental to vision. Published in eLife, the study provides an understanding of mechanisms underlying the pathologies of certain mutations within genes encoding key structural proteins in the ROS membrane that have been shown to lead to blindness. Read more.
SOURCE: University of California, Irvine, January 2022
NIH Researchers Develop Stem Cell Model of Albinism
Researchers at the National Eye Institute have developed the first patient-derived stem cell model for studying eye conditions related to oculocutaneous albinism (OCA). The “disease-in-a-dish” system will help illuminate how the absence of pigment in albinism leads to abnormal development of the retina, optic nerve fibers and other eye structures crucial for central vision, the authors say. Read more.
SOURCE: NIH, January 2022
Kodiak's Wet AMD Treatment Misses Primary Endpoint in Phase IIb/III
Kodiak says its drug KSI-301, a novel antibody biopolymer conjugate, didn't meet the primary efficacy endpoint of showing non-inferior visual acuity gains for wet AMD subjects dosed on extended regimens compared to aflibercept given every eight weeks. Read more.
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