Review of Ophthalmology Online



Vol. 22, #39  •   Monday, September 20, 2021


In this Issue:




Blood Pressure & Glaucomatous Progression

Researchers evaluated the effect of systemic arterial blood pressure on rates of progressive structural damage over time in glaucoma, as part of a retrospective cohort study.

A total of 7,501 eyes of 3,976 individuals with glaucoma or suspected of having glaucoma from the Duke Glaucoma Registry were included.

Linear mixed models were used to investigate the effects of BP on the rates of retinal nerve fiber layer loss from spectral-domain optical coherence tomography over time. Models were adjusted for intraocular pressure, gender, race, diagnosis, central corneal thickness, follow-up time and baseline disease severity.

Main outcome measures included effect of mean arterial pressure (MAP), systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) on rates of RNFL loss over time.

A total of 157,291 BP visits, 45,408 IOP visits and 30,238 SD-OCT visits were included. Here are some of the findings:
• Mean rate of RNFL change was -0.70 μm/y (CI, -0.72 to -0.67 μm/y).
• In univariable models, MAP, SAP and DAP during follow-up weren’t significantly associated with rates of RNFL loss.
• When adjusted for mean IOP during follow-up, each 10 mmHg lower in mean MAP (-0.06 μm/y; p=0.007) and mean DAP (-0.08 μm/y; p<0.001), but not SAP (-0.01 μm/y; p=0.355), was associated with significantly faster rates of RNFL thickness change over time.
• The effect of the arterial pressure metrics remained significant after additional adjustment for baseline age, diagnosis, sex, race, follow-up time, disease severity and corneal thickness.

Researchers wrote that, when adjusted for IOP, lower MAP and DAP during follow-up were significantly associated with faster rates of RNFL loss, suggesting that levels of systemic blood pressure may be a significant factor in glaucoma progression.

SOURCE: Jammal AA, Berchuck SI, Mariottoni EB, et al. Blood pressure and glaucomatous progression in a large clinical population. Ophthalmology 2021; Aug 30. [Epub ahead of print].




Systemic Health and Medication Use’s Impact on GA Rate in AMD

The associations of geographic atrophy progression with systemic health status and medication use are unclear. Investigators manually delineated GA in 318 eyes in the Age-Related Eye Disease Study. They calculated GA perimeter-adjusted growth rate as the ratio between GA area growth rate and mean GA perimeter between the first and last visit for each eye (mean follow-up=5.3 years). Patients' history of systemic health and medications was collected through questionnaires administered at study enrollment. Investigators evaluated the associations between GA perimeter-adjusted growth rate and 27 systemic health factors, using univariable and multivariable linear mixed-effects regression models.

Here are some of the findings:
• In the univariable model, GA perimeter-adjusted growth rate was associated with:
   o GA in the fellow eye at any visit (p=0.002);
   o hypertension history (p=0.03);
   o cholesterol-lowering medication use (p<0.001);
   o beta-blocker use (p=0.02);
   o diuretic use (p<0.001); and
   o thyroid hormone use (p=0.03).
• Among the six factors, GA in the fellow eye at any visit (p=0.008), cholesterol-lowering medication use (p=0.002) and diuretic use (p<0.001) were independently associated with higher GA perimeter-adjusted growth rate in the multivariable model.
• GA perimeter-adjusted growth rate was 51.1 percent higher in patients with vs. without cholesterol-lowering medication use history, and was 37.8 percent higher in patients with a history of diuretic use vs. those without.

Investigators reported that the GA growth rate may be associated with the fellow eye status, cholesterol-lowering medication use and diuretic use. However, they added that these possible associations don’t imply causal relationships, and future prospective studies are required to investigate the relationships further.

SOURCE: Shen LL, Xie Y, Sun M, et al. Associations of systemic health and medication use with the enlargement rate of geographic atrophy in age-related macular degeneration. Br J Ophthalmol 2021; Sep 6. [Epub ahead of print].


Complimentary CME Education Videos


Long-term Changes in the Refractive Effect of a Toric IOL on Astigmatism Correction

Scientists examined long-term changes in the astigmatism-correcting effect of a toric intraocular lens after stabilization of surgically induced astigmatic changes due to cataract surgery.

Unilateral eyes of 120 patients that received a toric IOL for against-the-rule or with-the-rule astigmatism were enrolled. Manifest refractive and anterior corneal astigmatism, and ocular residual astigmatism—which is mainly derived from internal optics—were examined preoperatively at approximately two months postoperatively (baseline), and at five to 10 years post-baseline. The astigmatism was broken into vertical/horizontal (Rx) and oblique components (Ry) compared between baseline, and five to 10 years post-baseline.

Here are some of the findings:
• In the eyes having ATR astigmatism, the mean Rx and Ry of the manifest refractive and corneal astigmatism significantly changed toward ATR astigmatism between the baseline, and five to 10 years post-baseline (p≤0.0304), but those of ocular residual astigmatism didn’t change significantly between the two time points.
• In the eyes having WTR astigmatism, the Rx and Ry of refractive, corneal and ocular residual astigmatism didn’t change significantly between the two time points.
• Double-angle plots revealed:
   o an ATR shift in refractive and corneal astigmatism;
   o no marked change in the ocular residual astigmatism in the eyes with ATR astigmatism; and
   o no change in astigmatism in the eyes with WTR astigmatism.

Scientists determined that the long-term changes with age in the effect of a toric IOL significantly deteriorated due to an ATR shift of corneal astigmatism in the eyes having ATR astigmatism, while it was maintained in eyes having WTR astigmatism. They added that the findings suggested ATR astigmatism should be overcorrected.

SOURCE: Hayashi K, Yoshida M, Hayashi S, et al. Long-term changes in the refractive effect of a toric intraocular lens on astigmatism correction. Graefes Arch Clin Exp Ophthalmol 2021; Sep 8. [Epub ahead of print].


Inhibition of Complement C3 in GA with NGM621

Researchers for NGM Biopharmaceuticals evaluated the safety and tolerability of single and multiple intravitreal injections of the company’s NGM621 in patients with geographic atrophy, and characterized the pharmacokinetics and immunogenic potential.

The multicenter, open-label, single- and multiple-dose Phase I study enrolled 15 patients at four sites in the United States. Participants had GA secondary to age-related macular degeneration, lesion size ≥2.5 mm2 and best-corrected visual acuity of four to 54 letters (20/80 to 20/800 Snellen equivalent) in the study eye, and no history of choroidal neovascularization in either eye. Patients who met eligibility criteria were treated in a single ascending-dose phase (2 mg, 7.5 mg, 15 mg) or received two doses of NGM621 15 mg four weeks apart in the multidose phase, and were followed for 12 weeks (85 days). Assessments included adverse events, best-corrected visual acuity, low luminance visual acuity, vital signs, clinical laboratory evaluations, GA lesion area (as measured by fundus autofluorescence), spectral-domain optical coherence tomography; and pharmacokinetic, immunogenicity and pharmacodynamic assessments.

All 15 participants completed the 12-week study. Here are some of the findings:
• No serious adverse events, drug-related adverse events or development of choroidal neovascularization in either eye were reported.
• Mean visual acuity and GA lesion area appeared stable through week 12 for all cohorts.
• Pharmacokinetic analyses indicated that NGM621 serum exposures appeared to be dose proportional, and no antidrug antibodies were identified at the evaluated time points.

Researchers reported, in this small, open-label, 12-week Phase I study, NGM621 was safe and tolerable when administered intravitreally up to 15 mg.

SOURCE: Wykoff CC, Hershberger V, Eichenbaum D, et al. Inhibition of complement C3 in geographic atrophy with NGM621: Phase 1 dose-escalation study results. Am J Ophthalmol 2021; Sept 9. [Epub ahead of print].




Industry News

Apellis Announces Topline Results from Phase III DERBY & OAKS

Apellis Pharmaceuticals reported topline results from the Phase III DERBY and OAKS studies evaluating intravitreal pegcetacoplan, an investigational targeted C3 therapy, in 1,258 adults with geographic atrophy secondary to age-related macular degeneration. The company says that monthly and bi-monthly treatment with pegcetacoplan met the primary endpoint in OAKS, significantly reducing GA lesion growth by 22 percent and 16 percent, respectively, compared to pooled sham at 12 months.
DERBY didn’t meet the primary endpoint, showing a reduction in GA lesion growth of 12 percent and 11 percent with monthly and every-other-month treatment, respectively, compared to pooled sham at 12 months. In a prespecified analysis of the combined DERBY and OAKS studies, monthly and every-other-month treatment with pegcetacoplan reduced GA lesion growth by 17 percent (p<0.0001) and 14 percent (p=0.0012), respectively, compared to pooled sham at 12 months, Apellis says. Based on these results, the company plans to submit a New Drug Application for pegcetacoplan for GA to the FDA in the first half of 2022. Read more.


Lineage Announces Data on OpRegen in Geographic Atrophy

Lineage Cell Therapeutics reported updated findings from its ongoing, 24-patient Phase I/IIa clinical study of lead candidate OpRegen. OpRegen is an investigational cell therapy consisting of allogeneic retinal pigment epithelium cells, administered in a single surgery to the subretinal space for the treatment of dry age-related macular degeneration with geographic atrophy. Lineage says that, overall, OpRegen was well-tolerated with no new unexpected ocular or systemic adverse events, or serious adverse events not previously reported. Read more.

Aerie Gives Update on its Dry-eye Drug Trial

Aerie Pharmaceuticals reported topline results of its Phase IIb clinical study, named COMET-1, for AR-15512 (TRPM8 Agonist) ophthalmic solution for dry eye. The study showed greatest efficacy in the higher concentration 0.003% b.i.d., which will be advanced to Phase III studies, Aerie says. Read more.


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