Review of Ophthalmology Online



Vol. 23, #12  •   Monday, March 28, 2022


In this Issue:




Long-term IOP Fluctuation and VF Progression in Advanced Glaucoma

Researchers wrote that IOP fluctuations increase the risk of visual field progression in advanced primary open-angle glaucoma even when the average IOP is maintained at a low level. They aimed to identify risk factors associated with progression of VF defects in patients with advanced POAG.

Researchers conducted a retrospective review of medical records to identify patients who met the Hodapp-Parrish-Anderson criteria for advanced POAG. A total of 122 eyes of 122 patients had undergone IOP measurement with Goldmann applanation tonometer (GAT), standard automated perimetry (SAP), Cirrus optical coherence tomography and fundus photography at six-month intervals. VF progression was defined as deterioration of a minimum of three VF locations more than baseline at 5 percent levels in four consecutive VFs with 24-2 SITA testing.

Here are some of the findings:
• Thirty-six of 122 eyes (29.5 percent, 51.9 ±13.9 years old) showed VF progression during 100.7 ±44.2 months of follow-up.
• The progression group showed greater long-term IOP fluctuations (2.6 ±1.4 mmHg) than the no-progression group (53.5 ±13.5 years; 2 ±1 mmHg, p=0.008).
• Disc hemorrhage was detected more frequently in the progression group (40.5 vs. 17.4 percent, p=0.005).
• Multivariate Cox regression analysis revealed long-term IOP fluctuations (HR, 2.567 percent; CI, 1.327 to 5.370; p=0.012) and disc hemorrhages (HR, 2.351; CI, 1.120 to 4.931; p=0.024) to be independent risk factors of VF progression.
• Patients who showed both disc hemorrhages and long-term IOP fluctuations were at greater risks of progression (HR, 2.675; CI, 1.072 to 6.457; p=0.035).

Researchers reported that long-term IOP fluctuations and disc hemorrhages were independent and additive risk factors of VF progression in advanced glaucoma even at low IOPs. They suggested that patients in whom these risk factors are identified require close monitoring and vigorous treatment.

SOURCE: Lee JS, Park S, Seong GJ, et al. Long-term intraocular pressure fluctuation is a risk factor for visual field progression in advanced glaucoma. J Glaucoma 2022; Mar 11. [Epub ahead of print].




Aflibercept for Retinal Nonperfusion in PDR

Investigators in Regeneron’s RECOVERY study say that retinal nonperfusion (RNP) is an important biomarker for diabetic retinopathy. Data suggests that consistent anti-VEGF pharmacotherapy can slow RNP development, the researchers note. RECOVERY evaluated the impact of aflibercept (Eylea, Regeneron) on RNP among eyes with proliferative DR.

This prospective randomized clinical trial with treatment crossover in the second year looked at 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. Means and 95 percent confidence intervals were calculated.

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 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, arms 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) of subjects in arm 1 and 81 percent (n=13) in arm 2.

Investigators wrote that through year two of RECOVERY, both treatment arms experienced significant increases in retinal nonperfusion. 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; 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].





Pre-Loaded DMEK with Endothelium-inwards Technique

Scientists evaluated factors affecting the outcomes of performing pre-loaded (pl) DMEK with the endothelium-inwards technique, as part of a retrospective clinical case series and comparative tissue preparation study.

Participants included 55 donor tissues for ex vivo study and 147 eyes of 147 patients indicated with Fuchs’ endothelial dystrophy, or pseudophakic bullous keratopathy with or without cataract.

Standardized DMEK peeling was performed with a 9.5-mm diameter, followed by a second trephination for loading the graft (8 to 9.5 mm diameter). The tissues were manually pre-loaded and preserved for four days or shipped for transplantation. Live/dead assay and immunostaining was performed on ex vivo tissues. For the clinical study, the tissues were delivered using the bi-manual pull-through technique followed by air tamponade at all centers.

Main outcome measures included tissue characteristics, donor and recipient factors, rebubbling rate, endothelial cell loss (ECL); and corrected-distance visual acuity at three, six and 12 months.

Here are some of the findings:
• At day four, significant cell loss (p=0.04) was observed in pl-DMEK with loss of biomarker expression seen in pre-stripped and pl-DMEK tissues.
• Re-bubbling was observed in 40.24 percent of cases.
• Average ECL was 45.87 at three months, 40.98 at six months and 47.54 percent at 12 months.
• CDVA improved significantly at three months postop (0.23 ±0.37 logMAR) (p<0.01) compared with baseline (0.79 ±0.61 logMAR).
• A significant association (p<0.05) between graft diameter, preservation time, recipient gender, gender mismatch and recipient age to re-bubbling rate was observed.

Scientists determined that graft loading to delivery time of pre-loaded DMEK tissues in endothelium-inwards fashion must be limited to four days after processing. They added that the rebubbling rate and overall surgical outcomes following pre-loaded DMEK can be multifactorial and center-specific.

SOURCE: Parekh M, Pedrotti E, Viola P, et al. Factors affecting the success rate of pre-loaded DMEK with endothelium-inwards technique: A multi-centre clinical study. Am J Ophthalmol 2022; Mar 11. [Epub ahead of print].


Complimentary CME Education Videos



Plasma Omega-3 Fatty Acids & Early AMD

Researchers examined the association between omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and age-related macular degeneration in the Multi-ethnic Study of Atherosclerosis (MESA) cohort.

MESA was a multicenter, prospective cohort study studying risk factors for cardiovascular disease in four ethnic groups. A total of 6,814 participants of white, African American, Hispanic/Latino and Chinese descent, ages 45 to 84 years, were recruited. Those found to have cardiovascular disease were excluded.

The study population included all MESA participants with baseline PUFA measurements and retinal photography at exam five (n=3,772). Fundus photographs were assessed for AMD using a standard grading protocol. Relative risk regression (log-link) determined associations between PUFA levels and AMD.

Researchers found a significant association between increasing DHA levels and increasing DHA + EPA levels with reduced risk for early AMD (n=214 participants with early AMD; n=99 [46.3 percent] were non-white). EPA levels alone weren’t significantly associated with AMD.

Researchers found that increasing levels of DHA were associated with reduced risk for early AMD in a multi-ethnic cohort. They wrote that the study represented the first racially diverse study demonstrating an association between omega-3 PUFAs and AMD risk.

SOURCE: Karger AB, Guan W, Nomura SO, et al. Association of plasma ω-3 fatty acids with early age-related macular degeneration in the Multi-Ethnic Study of Atherosclerosis (MESA). Retina 2022; Mar 9. [Epub ahead of print].




Industry News

Ribomic Provides Update on RBM-007 Program in Wet AMD

Ribomic announced positive results from TEMPURA along with updated data from its TOFU and RAMEN studies with RBM-007, an investigational anti-fibroblast growth factor-2 aptamer, in wet age-related macular degeneration. The company says that the data demonstrated a positive trend in two clinically relevant endpoints, best-corrected visual acuity and central subfield thickness. Read more.

Real World Ophthalmology to Hold Virtual Semi-annual Meeting

Real World Ophthalmology describes itself as a meeting for ophthalmology residents, Fellows or newly-minted ophthalmologists in their first years in practice. At its virtual meeting, scheduled for April 2, 2022, the organization says veteran ophthalmologists will provide tips on topics such as finding the right job, negotiating contracts, incorporating the latest drugs, mastering new technology in the OR, working with staff, building a referral network, dealing with complications and minimizing your medicolegal risk. Read more.

Akari to Present on AMD and OSD Programs at ARVO Annual Meeting

Akari Therapeutics announced Virginia Calder, professor of ocular inflammation, The Institute of Ophthalmology, UCL and Moorfields Eye Hospital, London, will give an oral and poster presentation at the Association for Research in Vision and Ophthalmology annual meeting, scheduled for May 1 to 4 in Denver, on Akari’s programs using long-acting PAS-nomacopan in age-related macular degeneration and geographic atrophy, and topical nomacopan for ocular surface diseases. Read more.

LumiThera LIGHTSITE III Meets Primary Endpoint

LumiThera announced positive findings from its LIGHTSITE III multicenter clinical trial in non-neovascular age-related macular degeneration subjects treated with the Valeda Light Delivery System. Statistically significant improvement was reported in BCVA at 13 months in the photobiomodulation (PBM)-treatment vs. sham-treatment group (p<0.003). A sustained mean increase in ETDRS letter score of 5.5 letters from baseline was seen at 13 months in PBM-treated subjects’ BCVA (p<0.0001). Read more.

Curative Biotechnology & NEI to Study Ocular Metformin in AMD

Curative Biotechnology announced a Cooperative Research and Development Agreement with the National Eye Institute in which the entities will initiate clinical studies to evaluate Curative's proprietary ocular metformin formulation for treatment of intermediate and late-stage age-related macular degeneration disease. Read more.

Visus Initiates Phase III Trials of Brimochol PF

Visus Therapeutics launched the first of two Phase III trials (BRIO-I and BRIO-II) for its lead asset, Brimochol PF, a preservative-free topical ophthalmic solution for the temporary treatment of presbyopia’s effects on near vision. The double-masked, randomized, multicenter, safety and efficacy studies are expected to enroll approximately 170 emmetropic phakic and 500 pseudophakic presbyopic patients. Read more.

Alcon’s Systane Complete PF Online and in U.S. Retail Stores

Alcon’s Systane Complete Preservative-Free Lubricant Eye Drops for dry eye are now available online and in U.S. retail stores in a multi-dose bottle.




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