Review of Ophthalmology Online



Vol. 23, #20  •   Monday, May 23, 2022


In this Issue:


A Message from Review's Chief Medical Editor, Mark H. Blecher, MD: The Decline of Function

In our own minds, we don’t age. That’s something other people do. Sometimes well, sometimes not. How do we know they’re aging? Gray hair? More weight? These are all physical attributes more apparent in others than in ourselves, at least as we see it. Most of us have this self-image from an earlier time that rarely matches reality. That’s why we’re sometimes shocked to catch a glimpse of ourselves in a mirror. It’s oh-so-easy to believe that were still 20 years younger than we are, no matter what age. I suppose this is an evolutionary coping mechanism meant to keep us from becoming despondent about the coming decline, and it works well until you can’t avoid it.

I can’t avoid it. It’s frustrating, annoying, and now soberingly limiting: my loss of near vision. Presbyopia. While it started out, as it always does, as a mild annoyance, I’m now functionally handicapped. It’s gotten to the point of being scared to not have readers or my iPhone nearby. Many of you have been there for years but despite the knowledge that it was coming, the functional reality is surprisingly shocking, not just for the visual limitations, but as a constant reminder that I’m getting old. Even if I feel pretty good, and still maintain my internal self-image of decades past, my failing accommodation is a harbinger of worse things to come, of the slide to decrepitude. OK, maybe I’m being a bit melodramatic, but it’s true. At least it gives me something to commiserate about with my patients …

Mark H. Blecher, MD
Chief Medical Editor
Review of Ophthalmology





Rates of Choroidal Microvasculature Dropout & RNFL Changes in Glaucoma

Researchers evaluated [GJ1] the association between rates of choroidal microvasculature dropout (MvD) change and rates of circumpapillary retinal nerve fiber layer (cpRNFL) loss in primary open-angle glaucoma eyes.

The cohort study included 91 eyes of 68 POAG patients with and without localized MvD at baseline, tracked over four visits and two-year follow-up using optical coherence tomography angiography and OCT scans. Area and angular circumference of MvD were evaluated on OCTA en-face and B-scan choroidal vessel density images during the follow-up period. Joint longitudinal mixed effects models were used to estimate the rates of change in MvD area or angular circumference and RNFL thickness. Univariable and multivariable regressions were completed to identify the factors contributing to cpRNFL thinning.

Here are some of the findings:
• MvD was identified in 53 (58.2 percent) eyes at baseline.
• Seventeen eyes (18.6 percent) that didn’t show MvD at baseline developed it over the follow-up period.
• Over a mean follow-up of four years:
   o the mean rate of change of MvD area was: 0.05 (CI, 0.04 to 0.06) mm2/year; and
   o the mean rate of change of angular circumference was 13.2 (CI, 10.7 to 15.8) degree/year.
• In multivariable models, the rate of cpRNFL thinning was significantly associated with the rates of change of MvD area (p=0.008) and angular circumference (p=0.009).

Researchers found that the rates of MvD area and angular circumference change over time were associated with concurrent rates of cpRNFL loss in POAG eyes.

SOURCE: Micheletti E, Moghimi S, Nishida T, et al. Rates of choroidal microvasculature dropout and retinal nerve fiber layer changes in glaucoma: Choroidal dropout and retinal nerve fiber layer changes. Am J Ophthalmol 2022; May 9. [Epub ahead of print].





Diagnostic Circulating Biomarker to Detect Sight-threatening DR

Investigators determined whether circulating biomarkers could be used to prioritize people with type 2 diabetes for retinal screening to detect sight-threatening diabetic retinopathy (STDR).

This cross-sectional study collected data from October 22, 2018, to December 31, 2021. All laboratory staff were masked to the clinical diagnosis, assigned a study cohort and provided with the database of clinical data. In this multicenter study conducted in three outpatient ophthalmology clinics in the U.K. and two centers in India, adults 40 years and older were categorized into four groups (STDR comprised groups three and four):
   (1) no history of diabetes;
   (2) type 2 diabetes of at least five years' duration with no evidence of DR;
   (3) nonproliferative DR with diabetic macular edema (DME); or
   (4) proliferative DR.

Thirteen previously verified biomarkers were measured using enzyme-linked immunosorbent assays. Severity of DR and presence of DME were diagnosed using fundus photographs and optical coherence tomography. Weighted logistic regression and receiver operating characteristic curve analysis were performed to identify biomarkers that discriminate STDR from no DR beyond clinical parameters of age, disease duration, ethnicity (in the U.K.) and hemoglobin A1c.

A total of 538 participants (mean age: 60.8 ±9.8 years; 319 men [59.3 percent]) were recruited into the study. A total of 264 participants (49.1 percent) were from India (group one: 54 [20.5 percent]; group two: 53 [20.1 percent]; group three: 52 [19.7 percent]; group four: 105 [39.8 percent]), and 274 participants (50.9 percent) were from the U.K. (group one: 50 [18.2 percent]; group two: 70 [25.5 percent]; group three: 55 [20.1 percent]; and group four: 99 [36.1 percent]).

ROC analysis (no DR vs. STDR) showed that, in addition to age, disease duration, ethnicity (in the U.K.) and hemoglobin A1c, inclusion of cystatin C had near-acceptable discrimination power in both countries (area under the ROC curve: 0.779; CI, 0.700 to 0.857 in 215 patients in the UK with complete data; AUC: 0.696; CI, 0.602 to 0.791 in 208 patients in India with complete data).

Results of this cross-sectional study suggested that serum cystatin C had good discrimination power in the U.K. and India. Investigators reported that circulating cystatin-C levels may be considered as a test to identify those who require prioritization for retinal screening for STDR.

SOURCE: Gurudas S, Frudd K, Maheshwari JJ, et al. Multicenter evaluation of diagnostic circulating biomarkers to detect sight-threatening diabetic retinopathy. JAMA Ophthalmol 2022; May 5. [Epub ahead of print].





DSEK: Fifteen-Year Outcomes

Scientists evaluated 15-year outcomes of Descemet’s stripping endothelial keratoplasty (DSEK).

They retrospectively reviewed a consecutive series of 350 DSEK cases in 290 patients (mean age 69 years), performed between December 2003 and December 2005 for Fuchs’ dystrophy (86 percent), pseudophakic/aphakic bullous keratopathy (10 percent) or failed penetrating keratoplasty (4 percent). Outcomes included best spectacle-corrected visual acuity, endothelial cell density (ECD) and graft failure (defined as regraft for any reason or persistent loss of stromal clarity).

At 15 years, 46 of 350 DSEK grafts (13 percent) had failed, 155 (44 percent) were in patients who died and 84 of the remaining 149 grafts (56 percent) were examined. Here are some of the findings:
• After accounting for loss to follow-up, the probability of graft failure was 7 percent at five years, 16 percent at 10 years and 23 percent at 15 years.
• The main risk factor for late endothelial failure was preoperative glaucoma (HR: 4.4 for medically managed and 24 for surgically managed glaucoma).
• The probability of an immunologic rejection episode was 7 percent by one year, 14 percent by 10 years and 17 percent by 15 years.
• The median donor ECD decreased from 3,030 cells/mm2 before DSEK to 1,973 cells/mm2 at six months (36-percent loss) and 705 cells/mm2 at 15 years (78-percent loss).
• The median BSCVA, including the eyes with ocular comorbidity, was 20/60 preoperatively, 20/40 at three through 12 months and 20/30 from two to 15 years.

Scientists concluded that DSEK provided excellent long-term visual rehabilitation and graft survival in this early cohort, performed when the technique was still being refined.

SOURCE: Price MO, Price FW Jr. Descemet stripping endothelial keratoplasty: Fifteen-year outcomes. Cornea 2022; Mar 31. [Epub ahead of print].


Complimentary CME Education Videos



Intravitreal Aflibercept in nAMD Patients: PERSEUS-IT 24-month Analysis

PERSEUS-IT was a prospective, observational, two-year study evaluating the effectiveness and treatment patterns of intravitreal aflibercept (IVT-AFL) in patients with neovascular age-related macular degeneration in routine clinical practice in Italy.

Treatment-naïve patients with nAMD receiving IVT-AFL per routine clinical practice were enrolled. The primary endpoint was mean change in visual acuity (decimal notation) from baseline to month 12 and 24. Outcomes were evaluated for the overall study population and independently for the two treatment cohorts: regular (three initial monthly doses; ≥7 injections by M12; and ≥4 injections between M12 and M24) and irregular (any other pattern).

Of 813 patients enrolled, 709 were included in the full analysis set (FAS); VA assessments were available for 342 patients at M12 (FAS1Y: 140 regular and 202 irregular) and 233 patients at M24 (FAS2Y: 37 regular and 196 irregular).
• In the overall FAS, the mean ±SD change in VA from baseline to M12 and M24 was +0.09 ±0.24 and +0.02 ±0.25 decimals.
• A statistically significant difference was found between the regular and irregular cohorts in both FAS1Y (p=0.0034) and FAS2Y (p=0.0222).
• Ocular treatment-emergent adverse events were reported in 4.1 percent (n=33/810 [safety set]) of patients.

Researchers observed clinically relevant functional and anatomic improvements within the first 12 months of IVT-AFL treatment in routine clinical practice in patients with treatment-naïve nAMD. The gains were generally maintained across the two-year study, and the safety profile of IVT-AFL was consistent with prior studies.

SOURCE: Nicolò M, Ciucci F, Nardi M, et al; PERSEUS-IT Study Investigators. PERSEUS-IT 24-month analysis: A prospective observational study to assess the effectiveness of intravitreal aflibercept in routine clinical practice in Italy in patients with neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2022; May 5. Epub ahead of print].




Industry News

AGTC Announces Skyline Trial Interim Results

Applied Genetic Technologies reported positive three-month interim data from its ongoing Phase II Skyline trial of AGTC-501, a recombinant AAV viral vector-based gene therapy targeting mutations in the RPGR gene in patients with X-linked retinitis pigmentosa. The company says that researchers reported robust improvements in visual sensitivity (the primary endpoint) in multiple patients three months after dosing. Read more.

RPB & Aerie Partner for Glaucoma Grant

Research to Prevent Blindness and Aerie Pharmaceuticals are partnering to provide early- to mid-career vision scientists with opportunities to pursue glaucoma research. The RPB / David L. Epstein Career Advancement Award in Glaucoma Research, sponsored by Aerie Pharmaceuticals, will include two awards—one available now and one in 2023—providing $150,000 each to scientists focusing on glaucoma research who have already received their first independent federal National Institutes of Health grant (the R01 grant), and are collecting new and novel data to apply for a second R01. This award is named in memory of David L. Epstein, MD, a glaucoma researcher who served on RPB’s grant review committees and who went on to co-found Aerie Pharmaceuticals. Read more.


Qlaris Reports Phase II QLS-101 Results

Qlaris Bio says it achieved positive results for QLS-101, the company’s investigational therapy for lowering intraocular pressure in the treatment of glaucoma, in a first-in-human, Phase II clinical trial. QLS-101 is a novel adenosine triphosphate (ATP)-sensitive potassium (KATP) channel modulator administered as a topical eyedrop targeting distal outflow resistance and episcleral venous pressure. Read more.

Ocuphire Talks Topline Data for Nyxol

Ocuphire Pharma recently announced topline results from the LYNX-1 Phase III pivotal clinical trial investigating its product candidate Nyxol for night (or dim light) vision disturbances. Across 12 U.S. clinical trials with approximately 1,100 subjects, over 650 subjects have now been treated with Nyxol. Read more.

New Hires and Promotions

• Perceive Biotherapeutics appointed Anne E. Fung, MD, as chief medical officer, who joins after eight years of leadership at Genentech, a member of the Roche Group. Learn more.
• Visiox Pharma appointed Ryan Bleeks as chief executive officer. Bleeks joins from RVL Pharmaceuticals, where he was responsible for building the infrastructure, sales force and launch execution of Upneeq. Read more.

Study Looks at Hill-RBF 3.0's Prediction Accuracy

Haag-Streit says a recent retrospective study of 153 patients in the JCRS found the Hill-RBF 3.0 IOL calculation formula was more accurate than the previous-generation Hill-RBF 2.0 and older generation formulas, and had similar prediction accuracy compared with new-generation formulas. Read more.




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