Review of Ophthalmology's Retina Online

Volume 18, Number 3

March 2022


Switching Stable Eyes on Aflibercept to Ranibizumab in nAMD

Scientists described outcomes of neovascular age-related macular degeneration eyes that were stable on aflibercept but switched to ranibizumab compared to eyes maintained on aflibercept over the same period.

In this retrospective cohort study, eyes switched from aflibercept to ranibizumab due to intraocular inflammation (IOI) concerns with aflibercept were identified. Data was gathered from three visits pre-switch, switch visit (Sw) and three visits post-switch (P1, P2, P3). Similar data was gathered on eyes eligible to switch but continued on aflibercept, with the middle visit considered the "presumed switch." Outcome measures included visual acuity and central foveal thickness (CFT).

A total of 142 eyes were analyzed with 71 in each of the switch and aflibercept groups. Here are some of the findings:

  • In the switch group, mean CFT increased from 165.7 µm at Sw to 184.7 µm at P1 (p=0.009), 180.9 µm at P2 (p=0.007) and 183.3 µm at P3 (p=0.004).
  • VA changed from logMAR 0.43 (20/54) at Sw to 0.49 (20/61) at P1 (p=0.02), 0.54 (20/69) at P2 (p=0.008) and 0.53 (20/68) at P3 (p=0.04).
  • In the aflibercept group, no significant change in CFT was found over the same period.
  • VA changed from logMAR 0.56 (20/72) at the "presumed switch" to 0.58 (20/76) at P1 (p=0.085), 0.62 (20/83) at P2 (p=0.001) and 0.59 (20/77) at P3 (p=0.14).

Scientists determined that nAMD eyes that were stable or improving on aflibercept that were switched to ranibizumab worsened, while those in a comparable group maintained on aflibercept remained fairly stable, suggesting a potential efficacy difference between the two drugs.

SOURCE: Salabati M, Obeid A, Mahmoudzadeh R, et al; Wills Switch Study Group. Outcomes after switching eyes that were stable on aflibercept to ranibizumab versus continuing aflibercept in neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2022; Mar 1. [Epub ahead of print].




OCT Predictors of Three-year Visual Outcomes for Type 3 MNV

Investigators identified baseline optical coherence tomography predictors of the three-year visual outcome for type 3 (T3) macular neovascularization secondary to age-related macular degeneration treated by anti-vascular endothelial growth factor therapy.

The retrospective longitudinal study included 40 eyes of 30 patients affected by exudative treatment-naïve T3 MNV. Baseline best-corrected visual acuity and several baseline OCT features were assessed and included in the analysis. Univariate and multivariate analyses served to identify risk factors associated with three-year BCVA.

Main outcome measures included baseline OCT features associated with bad or good visual outcome of type 3 MNV treated by anti-VEGF injections.

Here are some of the findings:
• Mean baseline BCVA of 0.34 ±0.28 logMAR significantly decreased to 0.52 ±0.37 logMAR at the end of three-year follow-up (p=0.002).
• In the univariate analysis, the following baseline features were associated with the three-year BCVA outcome:
   o baseline BCVA (p=0.004);
   o foveal involvement of exudation (p=0.004); and
   o presence of subretinal fluid (SRF)(p=0.004).
• In the multivariate model, the following factors were associated with three-year BCVA outcomes:
   o baseline BCVA (p=0.032);
   o central macular thickness (p=0.036);
   o number of active T3 lesions (p=0.034); and
   o presence of SRF (p=0.008).
• Three-year BCVA was significantly lower in 19 eyes with SRF at baseline (0.69 ±0.42 logMAR) compared with 21 eyes without SRF (0.37 ±0.24 logMAR, p=0.004).

Investigators identified structural OCT features associated with BCVA outcomes after three-year treatment with anti-VEGF injections. They wrote that, unlike some previous findings on neovascular AMD, the presence of SRF at baseline was the most significant independent negative predictor of functional outcomes. They added that their strategy may be used to identify less favorable T3 patterns requiring a more intensive treatment.

SOURCE: Sacconi R, Forte P, Tombolini B, et al. Optical coherence tomography predictors of 3-year visual outcome for type 3 macular neovascularization. Ophthalmol Retina 2022; Feb 25. [Epub ahead of print].


Quantitative Analysis of Branching Neovascular Networks in PCV After Photodynamic and Anti-VEGF Combination Therapy

Investigators studied serial changes in branching neovascular networks (BNN) by using optical coherence tomography angiography in patients with polypoidal choroidal vasculopathy who underwent combined photodynamic therapy and anti-vascular endothelial growth factor therapy.

In this retrospective study of 30 PCV patients, investigators collected OCTA images that had been obtained at baseline, and one, three and six months after treatment. At each time point, they recorded the vessel area, vessel percentage area, average vessel length and presence of polypoidal lesions on OCTA images, as well as best-corrected visual acuity, central retinal thickness (CRT) and central choroidal thickness (CCT).

Here are some of the findings:
• The detection rates on baseline OCTA images were 100 percent for BNN lesions and 71 percent for polypoidal lesions.
• The vessel area decreased during the first three months and increased six months post-treatment, demonstrating significant differences from baseline (p=0.031).
• The vessel percentage area reduced one and three months post-treatment (p=0.025), and increased six months post-treatment.
• Continuous polypoidal lesion regression was observed from one to three and six months post-treatment (p=0.031, p=0.004, p=0.002, respectively, in comparison with baseline).
• Patients with a decreasing vessel area over six months showed greater choroidal thickness than those with increasing vessel area (p=0.004).

Investigators found the branching neovascular networks showed initial regression that enlarged six months after therapy. They added that patients demonstrating continuous BNN regression exhibited a thicker choroid at baseline. Investigators advised that this difference should be considered during treatment for PCV and that OCTA could be used for follow-up evaluations.

SOURCE: Wang WY, Yang CH, Chen TC, et al. Quantitative analysis of branching neovascular networks in polypoidal choroidal vasculopathy by optical coherence tomography angiography after photodynamic therapy and anti-vascular endothelial growth factor combination therapy. Graefes Arch Clin Exp Ophthalmol. 2022; Feb 8. [Epub ahead of print].


Self-Imaging with Home OCT in nAMD

Notal Vision aimed to validate the performance of its Notal Vision Home OCT (NVHO) system for daily self-imaging at home, and to characterize retinal fluid dynamics in neovascular age-related macular degeneration, as part of a company-sponsored, prospective, observational study.

Fifteen participants who had at least one eye with nAMD undergoing anti-vascular endothelial growth factor treatments were included. The participants performed daily self-imaging at home with NVHO for three months. Scans were uploaded to the cloud, analyzed by the Notal OCT Analyzer (NOA), evaluated by human experts for fluid presence and compared with in-office OCT scans.

Main outcome measures included: weekly self-scan rate; image quality; scan duration; agreement between NOA and human expert grading for fluid presence; agreement between NVHO and in-office OCT scans for fluid presence, central subfield retinal thickness (CST) and retinal fluid volume; and characteristics of fluid dynamic during the study and in response to treatments.

Here are some of the findings:

  • The mean weekly scan frequency was 5.7 ±0.9 scans per week, and 93 percent of scans were eligible for NOA analyses.
  • Mean scan time was 42 seconds.
  • NOA and human experts agreed on the fluid status in 83 percent of scans and discrepancies were limited to trace amounts of fluid.
  • NVHO scans analyzed by NOA and in-office OCT scans graded by human experts agreed on the fluid status in 96 percent of cases.
  • CST and retinal fluid volume measurements from home OCT and in-office OCT scans demonstrated Pearson correlation coefficients of r=0.90 and r=0.92, respectively.
  • Novel parameters such as retinal fluid volume, area under the retinal fluid volume curve (AUC) demonstrated wide variations in fluid exudation and fluid load over time among patients.
  • Parameters, such as the rate of reduction in fluid volume in the first week after treatments and AUC between treatments, captured the speed and duration of response to anti-VEGF agents.

Researchers reported that daily home OCT imaging was feasible among patients with nAMD and that it “demonstrated good agreement with human expert grading for retinal fluid identification and excellent agreement with in-clinic OCT scans.”

SOURCE: Liu Y, Holekamp NL, Heier JS. Prospective, longitudinal study: daily self-imaging with home OCT in neovascular age-related macular degeneration. Ophthalmol Retina 2022; Feb 28. [Epub ahead of print].


Association of Pegcetacoplan with Progression of Incomplete RPE and Outer Retinal Atrophy in AMD

Investigators wrote that change in areas of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) within eyes with geographic atrophy might reflect similar changes among eyes with drusen but no GA. They evaluated the potential association of pegcetacoplan with progression of iRORA in eyes with GA secondary to AMD.

The post hoc analysis of the Apellis-sponsored Phase II multicenter, randomized, single-masked, sham-controlled FILLY trial of Apellis’ investigational intravitreal pegcetacoplan for 12 months took place from February 2 to July 7, 2020. Participants included 167 patients with GA secondary to AMD who received pegcetacoplan monthly (n=41) or every other month (n=56), or a sham injection (n=70) in the FILLY trial, and who completed the month 12 study visit and didn’t develop exudative AMD.

Interventions included intravitreal pegcetacoplan 15 mg or sham injection monthly or every other month for 12 months.

Masked readers analyzed spectral-domain optical coherence tomography scans in regions beyond a perimeter of 500 μm from the GA border according to the Classification of Atrophy Meetings criteria. Primary outcome measures were progression from iRORA to complete RPE and outer retina atrophy (cRORA) from baseline to six and 12 months.

Here are some of the findings:
• At baseline, iRORA was present in:
   o 45 percent of study eyes (18 of 40) in the pegcetacoplan monthly group;
   o 61.8 percent of study eyes (34 of 55) in the pegcetacoplan every other month group; and
   o 50.7 percent of study eyes (34 of 67) in the sham group.
• At 12 months, progression from iRORA to cRORA occurred in:
   o 50 percent of study eyes (nine of 18) in the pegcetacoplan monthly group (p=0.02 vs. sham);
   o 60.6 percent of study eyes (20 of 33) in the pegcetacoplan every other month group (p=0.06 vs. sham); and
   o 81.8 percent of study eyes (27 of 33) in the sham group.
• Compared with sham treatment, the relative risk of progression at 12 months from iRORA to cRORA was 0.61 (CI, 0.37 to 1.00) for eyes in the pegcetacoplan monthly group and 0.74 (CI, 0.54 to 1.02) for eyes in the pegcetacoplan every other month group.

Investigators found that eyes receiving intravitreal pegcetacoplan had lower rates of progression from iRORA to cRORA compared with controls, suggesting a potential role for pegcetacoplan therapy earlier in the progression of AMD prior to the development of GA.

SOURCE: Nittala MG, Metlapally R, Ip M, et al. Association of pegcetacoplan with progression of incomplete retinal pigment epithelium and outer retinal atrophy in age-related macular degeneration: A post hoc analysis of the FILLY randomized clinical trial. JAMA Ophthalmol 2022; Feb 3. [Epub ahead of print].


The Phenotypic Course of AMD for ARMS2/HTRA1: The EYE-RISK Consortium

Researchers investigated the phenotypic course and spectrum of age-related macular degeneration for the risk haplotype at ARMS2/HTRA1 in a large European consortium, as part of a pooled analysis of four case-control and six cohort studies.

Ten studies from the European Eye Epidemiology consortium provided data on 17,204 individuals ages 55+ years.

Researchers determined AMD features and macular thickness on multimodal images, and harmonized data on genetics and phenotype. They determined risks of AMD features for rs3750486 genotypes at the ARMS2/HTRA1 locus by logistic regression and compared them with a genetic risk score (GRS) of 19 variants at the complement pathway. And they estimated lifetime risk with Kaplan Meier product-limit analyses in prospective population-based cohorts. Main outcome measures included AMD features and stages.

Here are some of the findings:
• Of 2,068 individuals with late AMD, 64.7 percent carried the ARMS2/HTRA1 risk allele.
• For homozygous carriers, the odds ratio of:
   o geographic atrophy was 8.6 (CI, 6.5 to 11.4);
   o choroidal neovascularization was 11.2 (CI, 9.4 to 13.3); and
   o mixed late AMD was 12.2 (CI, 7.3 to 20.6).
• Cumulative lifetime risk of late AMD ranged from 4.4 percent for carriers of the non-risk genotype, to 9.4 percent and 26.8 percent for heterozygous and homozygous carriers, respectively. The latter group received the diagnosis of late AMD 9.6 (CI, 8 to 11.2) years earlier than carriers of the non-risk genotype.
• The risk haplotype wasn’t associated with hard or soft distinct drusen <125 um (OR, 1.2; CI, 0.9 to 1.7), but risks increased significantly for soft indistinct drusen ≥125 um (OR, 2.1; CI, 1.5 to 3; up to OR, 7.2; CI, 3.8 to 13.8) for reticular pseudodrusen.
• Compared with people with a high complement GRS, homozygous carriers of ARMS2/HTRA1 had a significantly higher risk of CNV (OR, 4.1; CI, 3.2 to 5.4), while risks of other characteristics including macular thickness weren’t significantly different.

Researchers found that carriers of the risk haplotype at the ARMS2/HTRA1 locus had a particularly high risk of late AMD at a relatively early age. The data suggested that risk variants at ARMS2/HTRA1 acted as a strong catalyst of progression once early signs were present. Researchers added that the genes’ phenotypic spectrum resembled that of complement genes, only with higher risks of CNV.

SOURCE: Thee EF, Colijn JM, Cougnard-Grégoire A, et al. The phenotypic course of age-related macular degeneration for ARMS2/HTRA1: The EYE-RISK Consortium. Ophthalmology 2022; Feb 28. [Epub ahead of print].


Photoreceptor Layer Thinning As a Biomarker for AMD

Researchers analyzed optical coherence tomography, electronic health records and genomic data to characterize the time sequence of changes in retinal layer thicknesses in age-related macular degeneration, as well as epidemiological and genetic associations between retinal layer thicknesses and AMD.

The cohort study included 44,823 U.K. Biobank individuals, ages 40 to 70 years (54 percent female) with median 10-year follow-up.

The Topcon Advanced Boundary Segmentation algorithm was used for retinal layer segmentation. Researchers associated nine retinal layer thicknesses: with prevalent AMD (present at enrollment) using a logistic regression model; and with incident AMD (diagnosed after enrollment) via a Cox proportional hazards model. Next, they associated AMD-associated genetic alleles, individually and as a polygenic risk score, with retinal layer thickness. All analyses were adjusted for age, age2, sex, smoking status and principal components of ancestry. Main outcome measures included prevalent and incident AMD.

Here are some of the findings:
• Photoreceptor segment (PS) layer thinning was observed throughout the lifespan of individuals analyzed, while retinal pigment epithelium and Bruch’s membrane complex (RPE+BM) thickening started after age 57.
• Each standard deviation of PS thinning and RPE+BM thickening was associated with incident AMD (PS: HR, 1.35; CI, 1.23 to 1.47, p=3.7x10-11; RPE+BM: HR 1.14; CI, 1.06 to 1.22, p=0.00024).
• The AMD polygenic risk score was associated with PS thinning (Beta -0.21 SD per two-fold genetically increased risk of AMD; CI, -0.23 to -0.19; p=2.8x10-74) and its association with RPE+BM was U-shaped (thinning with an AMD polygenic risk score <92nd percentile and thickening with AMD polygenic risk score >92nd percentile).
• The loci with strongest support for genetic correlations were the following AMD risk-raising variants:
   o CFH:rs570618-T, CFH:10922109-C and ARMS2/HTRA1:rs3750846-C for PS thinning; and
   o SYN3/TIMP3:rs5754227-T for RPE+BM thickening.

Researchers reported, epidemiologically, photoreceptor segment thinning preceded RPE+BM thickening by decades and was the retinal layer most strongly predictive of future AMD risk. They added, genetically, AMD risk variants were associated with decreased PS thickness. Overall, they wrote, the findings supported PS thinning as an early-stage biomarker for future AMD development.

SOURCE: Zekavat SM, Sekimitsu S, Ye Y, et al. Photoreceptor layer thinning is an early biomarker for age-related macular degeneration: Epidemiological and genetic evidence from UK Biobank optical coherence tomography data. Ophthalmology 2022; Feb 8. [Epub ahead of print].


Safety and Efficacy of Fluocinolone Acetonide Intravitreal Implant for DME: The PALADIN Study

Researchers in the Alimera-sponsored PALADIN study assessed the long-term safety and efficacy of the company’s 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (Iluvien) in patients with diabetic macular edema, as part of a three-year, Phase IV, nonrandomized, open-label observational study.

The study included patients with DME who previously received corticosteroid treatment without a clinically significant rise in intraocular pressure (IOP; all eyes, n=202 eyes of 159 patients; 36-month completion, n=94 eyes).

The prospective, observational study included patients who received a 0.19-mg FAc intravitreal implant at baseline, who were then were observed for safety-, visual-, anatomic- 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:

  • At 36 months after FAc implantation, study eyes showed a mean CST change of -60.69 μm (p<0.0001) and a mean BCVA change of +3.61 letters (p=0.0222) compared with baseline.
  • Overall median treatment frequency decreased from 3.4 treatments/year in the 36 months before FAc implantation to 1 treatment/year in the 36 months after FAc implant, a treatment burden reduction of 70.5 percent.
  • Furthermore, among the group that completed 36 months of treatment (n=94 eyes), 25.53 percent of eyes remained rescue-free through 36 months.
  • Mean IOP remained stable throughout the study, and IOP increases to more than 30 mmHg occurred in 10.89 percent of eyes.
  • IOP-related procedures were infrequent, with a surgical rate of 2.97 percent, with 1.49 percent attributable to steroid use (vs. surgeries attributable primarily to neovascular glaucoma).
  • IOP response of <25 mmHg after the steroid challenge predicted that 96.92 percent of eyes would have a similar outcome to 0.19-mg FAc implant at the last visit.
  • IOP increases that occurred were manageable with standard treatments (n=202 eyes).

Investigators reported 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 19. [Epub ahead of print].



Aflibercept for Retinal Nonperfusion in PDR: RECOVERY Trial

Retinal nonperfusion (RNP) is a biomarker for diabetic retinopathy (DR), and some data suggests that consistent anti-VEGF pharmacotherapy can slow RNP development. The Regeneron-funded RECOVERY study evaluated the impact of aflibercept (Eylea, Regeneron) on RNP among eyes with proliferative DR.

The study is a prospective, randomized clinical trial with treatment cross-over in the second year evaluated eyes with PDR and RNP.

At baseline, subjects were randomized 1:1 to monthly (arm 1) or quarterly (arm 2) intravitreal 2-mg aflibercept. At the beginning of year two, the treatment arms were crossed over so monthly dosed subjects subsequently received quarterly dosing while quarterly dosed subjects subsequently received monthly dosing.

Main outcome measures included change in total RNP area (mm2) through year two. Secondary outcomes included DR severity scale (DRSS) scores, best-corrected visual acuity, central subfield thickness, additional measures of RNP including ischemic index (ISI) and adverse events incidence.

Here are some of the findings:

  • Among all subjects from baseline to year two, mean RNP increased from 235 mm2 to 402 mm2 (p<0.0001) and ISI increased from 25.8 percent to 50.4 percent (p<0.0001).
  • Increases in mean RNP (p<0.0001) and ISI (p<0.0001) were also observed from year one to two.
  • Mean total RNP increased from 264 mm2 at baseline to 386 mm2 (p<0.0001) at year two in arm 1 and from 207 mm2 at baseline to 421 mm2 (p<0.0001) at year two in arm 2 (p=0.023, arm 1 vs. 2).
  • Increases in mean RNP for both treatment arms (p<0.0001) were also observed specifically within year two (p=0.32, arm 1 vs. 2).
  • Compared with baseline, DRSS scores at the end of year two improved in 82 percent (n=27) of subjects and remained stable in 18 percent (n=6), with no subject experiencing worsening; at two years, DRSS scores had improved by two or more steps in 65 percent (n=11) and 81 percent (n=13) of subjects in arms 1 and 2, respectively.

Investigators reported, through year two of RECOVERY, both treatment arms experienced significant increases in RNP. Despite expansion of RNP area in nearly all subjects, 82 percent demonstrated an improvement in DRSS levels from baseline with no subject experiencing worsening in DRSS.

SOURCE: Wykoff CC, Nittala MG, Boone CV, et al; For the RECOVERY Study Group. Final outcomes from the randomized RECOVERY trial of alfibercept for retinal nonperfusion in proliferative diabetic retinopathy. Ophthalmol Retina 2022; Mar 4. [Epub ahead of print].


Role of Peripapillary RNFL and Choroidal Thickness in DR Development and Progression

Investigators 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 the 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; of these, 748 didn’t have DR at baseline and 147 had DR at baseline. Here are some of the findings:
• During the two-year follow-up, 80 developed DR (10.7 percent), and 11 experienced DR progression (7.5 percent).
• After adjusting for confounding factors, a higher risk of incident DR was strongly associated with:
   o a lower average thickness of the pRNFL (risk ratio [RR] per 1 SD, 0.55; CI, 0.42 to 0.72; p<0.001); and
   o average pCT (RR per 1 SD, 0.49; CI, 0.34 to 0.70; p<0.001).
• Adding both metrics to the DR prediction model significantly improved the discriminant ability of the model for incidences of DR (area under the curve increased by 15.38 percent from 0.673 to 0.777; p<0.001).

Investigators wrote that neurodegeneration (evidenced by the thinning of pRNFL) and impaired choroidal circulation (evidenced by the thinning of pCT) were independently associated with DR onset. They added that assessing both metrics could 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.


Automatic Detection and Grading of DME Based on Deep Neural Network

Researchers proposed an automatic detection and grading method for diabetic macular edema based on a deep neural network, with the aim of improving DME grading and reducing the workload of ophthalmologists.

Enhanced green channels of fundus images were input into a “YOLO” network for training and testing. DME was graded according to the distance of the macula and hard exudate. Researchers used a multiscale fusion feature to improve detection of hard exudate and a “K-means++” algorithm to cluster anchor box size. Data on loss of the original network tracked regression of hard exudate bounding boxes. Researchers diversified training samples using data augmentation such as cropping, flipping and rotating of fundus images.

Researchers found the detection accuracy of the proposed method could reach 96 percent on the MESSIDOR dataset. The detection rates of hard exudate with high, median and low probability were 100, 79.12 and 60.40 percent, respectively. Researchers concluded that the proposed method exhibited very good detection stability for healthy and diseased fundus images.

SOURCE: Guo X, Lu X, Zhang B, et al. Automatic detection and grading of diabetic macular edema based on deep neural network. Retina. 2022 Jan 31. [Epub ahead of print].


Foveal Thickness Fluctuation in Anti-VEGF Treatment for BRVO

Researchers note that long-term results, optimal anti-VEGF treatment regimens and the comprehensive effects of macular edema recurrences are largely unknown, so the designed a study to examine the effects of foveal thickness fluctuation (FTF) on visual and morphologic outcomes following anti-VEGF for branch retinal vein occlusion macular edema administered via a pro re nata regimen.

The retrospective, observational case series analyzed 309 treatment-naïve patients (309 eyes) with BRVO-ME between 2012 and 2021, at a multicenter retinal practice.

FT was assessed via optical coherence tomography at each study visit.

Researchers evaluated the logMAR best-corrected visual acuity and defect length of the foveal ellipsoid zone (EZ) band via OCT.

Here are some of the findings:
• At baseline, the mean logMAR BCVA was 0.30 ±0.30 and the mean FT was 503 ±162 μm.
• The number of anti-VEGF injections for BRVO-ME was 5.8 ±4.6 during the mean follow-up period (50.6 ±22.2 months).
• At the final exam, the mean logMAR BCVA and FT values were significantly improved compared with the baseline.
• Multiple regression analyses showed that age, baseline logMAR BCVA and FTF were significantly associated with the final logMAR BCVA (β=0.20, 0.35 and 0.30, respectively).
• FTF (divided into groups 0 to 3 in ascending order of FTF) was significantly associated with the logMAR BCVA and the defect length of the foveal EZ band at the final exam.
• The defect lengths of the foveal EZ band were longitudinally shortened in groups 0 to 1, and were slightly prolonged in groups 2 to 3.
• The logMAR BCVA maintained improvements in groups 0 to 1, and worsened slightly in groups 2 to 3.

Researchers found that FTF was significantly associated with visual acuity and foveal photoreceptor status. They suggested that identifying the characteristics of eyes with a larger FTF and controlling FTF more strictly may improve the morphologic and functional prognosis of eyes with BRVO.

SOURCE: Nagasato D, Muraoka Y, Tanabe M, et al. Foveal thickness fluctuation in anti-vascular endothelial growth factor treatment for branch retinal vein occlusion: A long-term study. Ophthalmol Retina 2022; Feb 23. [Epub ahead of print].


Pars Plana Vitrectomy with and without Supplemental Scleral Buckle for the Repair of RRD

In a recent study of retinal detachment, researchers wrote that it’s unclear whether differences exist in safety and efficacy between pars plana vitrectomy (PPV) alone vs. PPV with supplemental scleral buckle (PPV-SB) for the treatment of rhegmatogenous detachments. They compared the safety and efficacy of the surgical procedures in this meta-analysis.

Researchers systematically searched (2000-June 2021) MEDLINE, EMBASE and Cochrane CENTRAL. The primary outcome was the final best-corrected visual acuity, while secondary outcomes were re-attachment rates and complications. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomized controlled trials (RCTs) and the ROBINS-I tool for non-randomized studies.

A total of 15,661 eyes from 38 studies (32 observational studies, six randomized control trials) were included. The median follow-up was six months. Here are some of the findings:

  • Final best-corrected visual acuity was similar between PPV and PPV-SB (weighted mean difference [WMD]: -0.03; CI, -0.14 to 0.07; p=0.55).
  • A significant difference was found in single operation success rate (SOSR) (88.2 percent vs. 86.3 percent; reattachment rate ([RR]: 0.97; CI, 0.95 to 1.00; p=0.03) favoring PPV-SB; however, no significant difference was found in final reattachment rate (RR: 1.00; CI, 0.99 to 1.01; p=0.56).
  • PPV required a significantly higher number of operations to achieve final anatomical re-attachment (WMD: 0.13; CI, 0.02 to 0.24; p=0.02).
  • PPV was significantly less likely to be associated with macular edema (RR: 0.47; CI, 0.25 to 0.88; p=0.02) and epiretinal membrane formation (RR: 0.70; CI, 0.52 to 0.94); p=0.02), but these differences were no longer significant in studies published after 2010 or in RCTs.
  • Significant PVR, lens and macular attachment status didn’t mediate differences in effect.

Researchers reported no significant differences were found in final visual acuity outcomes between PPV and PPV-SB. They wrote that PPV-SB was associated with a greater SOSR relative to standalone PPV, although the magnitude of effect was small with a high number needed to treat. Researchers added that the final reattachment rate was similar and that the risk of complications was similar between procedures in recent studies and in RCTs.

SOURCE: Eshtiaghi A, Dhoot AS, Mihalache A, et al. Pars plana vitrectomy with and without supplemental scleral buckle for the repair of rhegmatogenous retinal detachment: A meta-analysis. Ophthalmol Retina 2022; Feb 25. [Epub ahead of print].




Kodiak’s KSI-301 Fails to Meet Primary Endpoint

Kodiak Sciences announced results from its randomized, double-masked, active comparator-controlled Phase IIb/III clinical trial evaluating the efficacy, durability and safety of KSI-301, a novel antibody biopolymer conjugate, in treatment-naïve subjects with neovascular age-related macular degeneration. KSI-301 didn’t meet the primary efficacy endpoint of showing non-inferior visual acuity gains for subjects dosed on extended regimens compared to aflibercept given every eight weeks. Read more.

SOURCE: Kodiak Sciences, February 2022

Xipere Now Available

After having been approved in October of last year, Bausch + Lomb and Clearside's Xipere (triamcinolone acetonide injectable suspension) is now available for sale. Xipere is approved for the treatment of macular edema associated with uveitis, and uses the suprachoroidal space as its route of administration. Read more.


Unity Announces Additional Data from Phase I UBX1325 Trial

Unity Biotechnology announced additional 24-week clinical data from the Phase I study of UBX1325, presented at the Angiogenesis, Exudation, and Degeneration 2022 conference, held virtually. Among other findings, Unity says UBX1325 was well-tolerated without signs of intraocular inflammation or other related ocular adverse effects. In DME, researchers observed a mean improvement of 9.5 ETDRS letters from baseline at six months in the higher-dose cohorts (5, 10 mcg) and 6.9 ETDRS letters from baseline at six months in all dose cohorts. In AMD, researchers reported improvements or stabilization of both BCVA and CST through six months post-injection. Read more.

SOURCE: UNITY Biotechnology, February 2022


Ray Therapeutics and Forge Biologics Partner

Ray Therapeutics and Forge Biologics, a gene therapy-focused contract development and manufacturing organization, announced a manufacturing partnership to advance Ray Therapeutics’ lead optogenetics gene therapy program, Ray-001, into clinical trials for patients with retinitis pigmentosa. Read more.

SOURCE: Forge Biologics, March 2022


Wireless Visual Prosthesis Brain Implant Successfully Implanted
The Intracortical Visual Prosthesis (ICVP), an implant that bypasses the retina and optic nerves to connect directly to the brain’s visual cortex, was successfully surgically implanted in the first participant at Rush University Medical Center in February. The surgery is part of a Phase I feasibility study of the prosthesis for people with blindness. The system was developed by a multi-institution team led by Philip R. Troyk, PhD, executive director of the Pritzker Institute of Biomedical Science and Engineering at Illinois Institute of Technology, and represents nearly three decades of research. The intracortical visual implant is the first to use a group of fully implanted miniaturized wireless stimulators. Read more.  

SOURCE: Illinois Institute of Technology, February 2022



Foundation Fighting Blindness and InformedDNA Partner

Foundation Fighting Blindness is partnering with ProQR Therapeutics and InformedDNA to accelerate patient identification and enrollment in clinical research for people with Usher syndrome or non-syndromic retinitis pigmentosa due to mutations in exon 13 of the USH2A gene. The Foundation is using its exclusive My Retina Tracker Registry to identify patients with mutations in USH2A-exon 13 to accelerate identification of candidates for the trials.  Read more.

SOURCE: Foundation Fighting Blindness, March 2022


Kato to Start Human Studies

Kato Pharmaceuticals announced the FDA has given the company the go-ahead to conduct human studies using Resolv ER for the treatment of vitreomacular attachment. Read more.

SOURCE: Kato Pharmaceuticals, February 2022


Harrow Health Files NDA for Pain Drug

Harrow Health announced that the FDA accepted its New Drug Application filing for AMP-100, the company’s drug candidate for ocular surface anesthesia and intraoperative pain management during ocular surgery. The FDA assigned the application standard review and a Prescription Drug User Fee Act target action date of October 16. Read more.


SOURCE: Harrow Health, February 2022

LumiThera Acquires Diopsys

LumiThera says its acquisition of Diopsys creates a complementary diagnosis and monitoring platform to its Valeda Light Delivery System. Diopsys’ electroretinography capability is diagnostic test that measures the electrical activity of the retina of the eye in response to a light stimulus. Read more.


SOURCE: LumiThera, March 2022

New Appointments

• Aerie Pharmaceuticals announced that Gary Sternberg, MD, MBA, joined the company as chief medical officer. Dr. Sternberg joins from RainBio, where he served as acting CEO. Read more.
• Opthea named Joel Naor, MD, MSc, as chief medical officer. Dr. Naor most recently served as vice president of clinical science and development operations at Kodiak Sciences. Read more.
• EyePoint Pharmaceuticals appointed Isabelle Lefebvre as chief regulatory officer. Previously, Lefebvre was vice-president, head of regulatory science at Hengrui USA. Read more.
• Outlook Therapeutics announced Alicia Tozier was appointed senior vice president, Marketing and Market Access. Read more.

SOURCE: Aerie Pharmaceuticals, February 2022; Opthea Limited, EyePoint Pharmaceuticals and Outlook Therapeutics, all March 2022





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