From the editors of Review of Ophthalmology:
APRIL IS SPORTS EYE SAFETY MONTH
In this issue: (click heading to view article)
Three-year Outcome Comparison Between F-DMEK and M-DMEK
Researchers evaluated three-year outcomes for femtosecond laser-assisted Descemet’s membrane endothelial keratoplasty compared with manual Descemet’s membrane endothelial keratoplasty in individuals with Fuchs’ endothelial corneal dystrophy.
The retrospective, interventional study included eyes with Fuchs’ and cataract that underwent either F-DMEK or M-DMEK combined with cataract extraction at the Toronto Western Hospital or Kensington Eye Institute, and that had at least 18 months' follow-up. Exclusion criteria included complicated anterior segments, previous vitrectomy, previous keratoplasty, corneal opacity or any other visually significant ocular comorbidity.
Participants included a total of 16 eyes of 15 individuals in the F-DMEK group (average follow-up 33 ±9 months), and 45 eyes of 40 individuals in the M-DMEK group (average follow-up 32 ±7 months). Here were some of the findings:
• No issues were reported with the creation of femtosecond descemetorhexis (in the F-DMEK group); all descemetorhexis cuts were complete.
• Best spectacle-corrected visual acuity improvements didn’t differ significantly between the groups at one year (p=
0.849), two years (p=
0.465) or three years (p=
• Rates of significant detachment were: in F-DMEK, one of 16 eyes (6.25 percent); and in M-DMEK, 16 of 45 eyes (35.6 percent) (p=
• Rebubbling rates were one of 16 eyes (6.25 percent) in F-DMEK and 15 of 45 eyes (33.3 percent) in M-DMEK (p=
• Cell-loss rates following the procedures were: at one year, 26.8 percent (F-DMEK) and 36.5 percent (M-DMEK)(p=
0.042); at two years, 30.5 percent (F-DMEK) and 42.3 percent (M-DMEK)(p=
0.008); and at three years, 37 percent (F-DMEK) and 47.5 percent (M-DMEK) (p=
• Graft failure rate was zero in F-DMEK and 8.9 percent in M-DMEK (all were primary failures; p=
Researchers determined that F-DMEK showed good efficacy with reduced detachment, rebubble and cell-loss rates compared with M-DMEK.
SOURCE: Sorkin N, Mednick Z, Einan-Lifshitz A, et al. Three-year outcome comparison between femtosecond laser-assisted and manual Descemet membrane endothelial keratoplasty. Cornea 2019; Apr 9. [Epub ahead of print].
Retinal Nonperfusion Characteristics on Ultra-widefield Angiography in Severe NPDR and PDR
Investigators identified a threshold of retinal nonperfusion for the presence of retinal neovascularization, and the distribution and area of retinal nonperfusion in eyes with severe nonproliferative diabetic retinopathy, PDR, neovascularization of the optic disc and retinal neovascularization elsewhere.
This cross-sectional image analysis was performed between Sept. 24, 2018, and Oct. 24, 2018, in a multicenter national study in the United Kingdom. Baseline images were obtained from two completed randomized clinical trials (Ranibizumab for Diabetic Macular Edema Panretinal Photocoagulation [RDP] study and Clinical Efficacy of Intravitreal Aflibercept vs. Panretinal Photocoagulation for Best Corrected Visual Acuity in Patients With Proliferative Diabetic Retinopathy at 52 Weeks [CLARITY] study). The RDP study recruited eyes with severe NPDR between April 1, 2014, and Dec. 31, 2015, and the CLARITY study recruited eyes with PDR between Aug. 22, 2014, and Nov. 20, 2015. The study included ultra-widefield angiography images of eyes with no prior panretinal photocoagulation treatment.
Main outcomes and measures included the total area of retinal nonperfusion, the area of posterior pole retinal nonperfusion and the area of peripheral retinal nonperfusion.
A total of 92 individuals (92 eyes) were included in the study: 59 in the PDR group (mean age: 42 ±15 years; 20 female [33.9 percent] and 33 in the NPDR group (mean age: 63 ±10 years; 30 female [9.1 percent]). Forty eyes had NVE and 19 had NVD with or without NVE. Here were some of the findings:
• Investigators identified a retinal nonperfusion threshold of 118.3 disc areas with a specificity of 84.9 percent (CI, 68.1 to 94.9 percent) for PDR.
• The median area of retinal nonperfusion was 67.8 DA (CI, 44.2 to 107.3 DA) in the NPDR eyes and 147.9 DA (CI, 127.4 to 173.5 DA) for eyes with proliferative changes, with a difference of 69.0 DA (CI, 42.2 to 97.7 DA; p<0.001).
• No difference was found in the median area of posterior nonperfusion between NPDR and PDR, with a difference of 0 DA (CI, -6.7 to 5.2 DA; p=0.56).
• Regarding peripheral nonperfusion, NPDR eyes measured 64.1 DA and PDR eyes measured 130.6 DA, with a difference of 70.8 DA (CI, 48.4 to 94.9 DA; p<0.001).
• Eyes with NVD had the largest total area of retinal nonperfusion, with a difference of 65.1 DA (CI, 28.6 to 95.8 DA; p<0.001) compared with eyes with only NVE.
Investigators wrote that these findings suggested that eyes with at least 107.3 DA of nonperfusion were at risk of proliferative disease, and eyes with NVD had the largest area of retinal nonperfusion.
SOURCE: Nicholson L, Ramu J, Chan EW, et al. Retinal nonperfusion characteristics on ultra-widefield angiography in eyes with severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy.
JAMA Ophthalmol 2019; Apr 11. [Epub ahead of print].
ET-1 Concentration in AH Predicts Late Low IOP in POAG Post-Trabeculectomy
Scientists aimed to evaluate potential risk factors for postoperative, late low intraocular pressure in individuals with primary open-angle glaucoma after trabeculectomies.
Adults who were diagnosed with POAG and scheduled to undergo primary unilateral trabeculectomy in the researchers’ hospital were consecutively included. Blood samples prior to the surgery and aqueous humor samples during the surgery of each participant were collected. Patient demographics, preoperative assessments and laboratory tests were compared in individuals with or without late low IOP. The risk factors for late low IOP were evaluated using logistic regression modeling. The predictive value of ET-1 in aqueous humor for late low IOP was evaluated by ROC curve analysis. Here were some of the findings:
• Of 222 enrolled individuals, there were 39 cases of late low IOP, with an incidence of 17.6 percent (39/222).
• The multivariate logistic regression analysis indicated that ET-1 concentrations in aqueous humor was the only independent risk factor for late low IOP after trabeculectomy (OR: 0.89, CI: 0.79 to 0.98; p=0.021).
• ROC curve analysis showed that ET-1 concentration in aqueous humor was a predictor for late low IOP after trabeculectomy, with an area under the curve of 0.639, a specificity of 84.62 percent and a sensitivity of 39.89 percent, respectively (p=0.006).
Scientists wrote that their findings indicated that ET-1 concentration in aqueous humor was an independent risk factor for late low IOP in POAG after trabeculectomy.
SOURCE: Liu Y, Han B, Li, et al. Endothelin-1 concentration in aqueous humor predicts postoperative late low intraocular pressure in primary open angle glaucoma after trabeculectomy. J Glaucoma 2019; Apr 3. [Epub ahead of print].
HAWK and HARRIER: Trials of Brolucizumab for nAMD
Two similarly designed, Phase III trials (HAWK and HARRIER) compared brolucizumab, a single-chain antibody fragment that inhibits vascular endothelial growth factor-A, with aflibercept to treat neovascular age-related macular degeneration, as part of double-masked, multicenter, active-controlled, randomized trials sponsored by brolucizumab’s maker, Novartis.
Participants (n=1,817) included individuals with untreated, active choroidal neovascularization due to AMD in the study eye. Individuals were randomized to intravitreal brolucizumab 3 mg (HAWK only), 6 mg or aflibercept 2 mg. After loading with three monthly injections, brolucizumab-treated eyes received an injection every 12 weeks (q12w) and were interval-adjusted to every eight weeks (q8w) if disease activity was present; aflibercept-treated eyes received q8w dosing.
The primary hypothesis was noninferiority in the mean best-corrected visual acuity change from baseline to week 48 (margin: four letters). Other key endpoints included the percentage of individuals who maintained q12w dosing through week 48 and anatomical outcomes. Here were some of the findings:
• At week 48, each brolucizumab arm demonstrated noninferiority to aflibercept in BCVA change from baseline (least squares [LS] mean: +6.6 [6 mg] and +6.1 [3 mg] letters with brolucizumab vs. +6.8 letters with aflibercept in HAWK; +6.9 [brolucizumab 6 mg] vs. +7.6 [aflibercept] letters in HARRIER; p<0.001 for each comparison).
• More than half of the brolucizumab 6 mg-treated eyes were maintained on q12w dosing through week 48 (56 percent in HAWK and 51 percent in HARRIER).
• At week 16, following identical treatment exposure, fewer brolucizumab 6 mg-treated eyes had disease activity vs. aflibercept in HAWK (24 percent vs. 34.5; p=0.001) and HARRIER (22.7 percent vs. 32.2 percent; p=0.002).
• Greater central subfield thickness reductions from baseline to week 48 were observed with brolucizumab 6 mg vs. aflibercept in HAWK (LS mean: -172.8 μm vs. -143.7 μm; p=0.001) and HARRIER (LS mean: -193.8 μm vs. -143.9 μm; p<0.001).
• Anatomical retinal fluid outcomes favored brolucizumab over aflibercept.
• Overall adverse event rates were generally similar with brolucizumab and aflibercept.
Source: Dugel PU, Koh A, Ogura Y, et al. HAWK and HARRIER: Phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 2019; Apr 12. [Epub ahead of print].
Novartis Announces FDA Filing of Brolucizumab for Wet AMD
Novartis announced that the FDA accepted the company's Biologics License Application for brolucizumab (RTH258) for the treatment of wet age-related macular degeneration. Seeking to make brolucizumab available as quickly as possible, Novartis used a priority review voucher to expedite FDA review. If approved by the FDA, Novartis anticipates launching brolucizumab by the end of 2019. The regulatory application is primarily based on Phase III data from the HAWK and HARRIER trials (described above). The primary endpoint of these studies was non-inferiority to aflibercept in mean change in best-corrected visual acuity from baseline to week 48. HAWK and HARRIER are the first and only global head-to-head trials in patients with wet AMD that prospectively demonstrated efficacy at week 48 starting with a 12-week dosing regimen, Novartis says. Read more.
Ophthotech Obtains Exclusive Global License to AAV Gene Therapy Program for BEST1-related Retinal Diseases
Ophthotech announced that the company converted its option and entered into an exclusive global license agreement with the University of Pennsylvania, including the Perelman School of Medicine at the University of Pennsylvania, the University of Pennsylvania School of Veterinary Medicine and the University of Florida Research Foundation, for rights to develop and commercialize novel adeno-associated virus gene therapy product candidates for the treatment of Best vitelliform macular dystrophy and other diseases related to mutations to the BEST1 gene. Read more.
Alimera Appoints Dr. Kaba as CMO
Alimera Sciences appointed Samer Kaba, MD, as chief medical officer, a new position at the company, effective April 4. Dr. Kaba is a board-certified neurologist with more than 15 years of pharmaceutical industry experience leading diverse teams and global projects. Prior to joining Alimera, Dr. Kaba served as chief medical officer at Cortexyme, and global head of clinical development and medical affairs at Osmotica Pharmaceuticals. Read more.
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