Review of Ophthalmology Online



Vol. 22, #16  •   Monday, April 19, 2021


In this Issue:


Earlier Detection of Glaucoma Progression Using High-Density 3D SD-OCT

Researchers compared onset times of glaucoma progression among different glaucoma tests: disc photography (DP), visual field testing, two-dimensional retinal nerve fiber layer thickness and three-dimensional spectral-domain optical coherence tomography neuroretinal rim measurements performed with the Heidelberg Spectralis. One of the authors’ research has been sponsored by Heidelberg, and he licenses technology to the company, but the researchers say that Heidelberg had no influence over the conduct of this study.

A total of 124 of 124 open-angle glaucoma patients were included in the prospective longitudinal cohort study.

Over a five-year period, 124 open-angle glaucoma patients had yearly DP, VFs, SD-OCT RNFL thickness scans and optic nerve volume scans (Spectralis, Heidelberg Engineering), performed on the same day. From high-density optic nerve volume scans, custom-built software calculated the minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter. Patients were classified as glaucoma progressors or non-glaucoma progressors using event-based analysis. Progression by DP and VF occurred when three masked glaucoma specialists unanimously concurred. Progression by RNFL and MDB thickness occurred if there was change greater than test-retest variability. Kaplan-Meier curves were constructed to analyze time-to-progression data. Kappa coefficients were used to measure agreement of progressing eyes among modalities.

The main outcome measure was time to glaucoma progression among all four modalities.

Here were some of the findings:
• Global MDB thickness detected glaucoma progression in the highest percentage of eyes (52.4 percent) compared with DP (16.1 percent, p<0.001) and global RNFL thickness (15.3 percent, p<0.001).
• Global MDB thickness detected glaucoma progression earlier than DP (23 vs. 44 months; p<0.001) or global RNFL thickness (23 vs. 33 months; p<0.001).
• Among MDB progressing eyes, 46.2 percent were simultaneously or later confirmed by other conventional modalities.
• Agreement of glaucoma progressing eyes for all four modalities in paired fashion was slight to fair (k=0.095 to 0.300).

Researchers found that high-density 3D SD-OCT neuroretinal rim measurements detected glaucoma progression approximately one to two years earlier compared with current clinically available structural tests (i.e., disc photos and 2D RNFL thickness measurements).

SOURCE: Ratanawongphaibul K, Tsikata E, Zemplenyi M, et al. Earlier detection of glaucoma progression using high-density 3D spectral-domain optical coherence tomography optic nerve volume scans. Ophthalmol Glaucoma 2021; Mar 24. [Epub ahead of print].




Recurrent nAMD After Discontinuation of VEGF Inhibitors Managed in a T&E Regimen

Investigators assessed the recurrence rate of active macular neovascularization in patients with neovascular age-related macular degeneration previously followed in a treat-and-extend regimen in which treatment had been stopped due to disease stability, as part of a prospective cohort study.

A total of 105 nAMD patients previously followed in a treat-and-extend regimen with aflibercept injections were included. All patients with a dry macula on three consecutive visits 12 weeks apart were eligible to participate. Patients were examined at baseline, and then monitored for disease recurrence four, six, eight, 10 and 12 months after the last injection.

Main outcome measures included the proportion of patients with recurrent disease within 12 months after the last injection, and BCVA change at the time of recurrence and after resumed therapy.

Here were some of the findings:
• Evidence of recurrent nAMD was seen in 54/102 patients (52.9 percent) after 12 months of follow-up.
• The mean time to recurrence after the last injection was 6.7 ±2.2 months. The best-corrected visual acuity decreased from 71.7 ±10 ETDRS letters at baseline to 68.1 ±11.1 letters at the recurrence (p=0.12).
• After treatment was resumed BCVA increased to 71.4 ±10 letters (p=NS compared to baseline).
• Patients with a pigment epithelial detachment at baseline had a 74 percent (14/19) recurrence rate compared to 48 percent (40/83) in subjects without a PED (p<0.05).
• Only 22/54 (40.7 percent) of the patients with recurrent disease had symptoms of visual loss or metamorphopsia.

Investigators reported that recurrent nAMD was common in previously stable patients when anti-VEGF injections were suspended. They wrote that it was difficult to predict which patients would have a recurrence, as most didn’t have symptoms in the early stages of reactivation. Investigators stressed the importance of long-term follow-up and noted that early detection of recurrent disease can improve the chances of maintained visual function.

SOURCE: Aslanis S, Amrén U, Lindberg C, et al. Recurrent neovascular age-related macular degeneration after discontinuation of VEGF inhibitors managed in a treat and extend regimen. Ophthalmol Retina 2021; Mar 25. [Epub ahead of print].




Corneal Densitometry Correlation to Specular Microscopy Values & Age

Scientists looked at correlations between specular microscopy endothelial parameters and age, and corneal densitometry values presented from a Scheimpflug device, in different levels of the cornea.

Two hundred eighty-four eyes of 142 healthy subjects were included in the observational, prospective study. Corneal densitometry was evaluated with the Scheimpflug imaging system in the central 0 to 2 mm annular zone of the cornea; endothelial cell properties were assessed with a noncontact specular microscope.

Here were some of the findings:
• Corneal densitometry values of all corneal layers were statistically significant and positively correlated with age.
• In univariate linear regression analysis of the corneal densitometry values and endothelial parameters, only endothelial cell density (CD) was statistically significant and inversely correlated with densitometry values in all corneal layers.
• In stepwise multivariate linear regression analysis, after adjustment for age, hexagonality was statistically significant and inversely correlated with posterior densitometry values, while coefficient of variation was positively and significantly correlated with the anterior densitometry values.
• When repeating stepwise multivariate linear regression analysis without adjusting for age, CD was negatively and significantly correlated with corneal densitometry values of all layers, while coefficient of variation was positively and significantly correlated with anterior and total corneal densitometry values.

Scientists concluded that corneal densitometry increased with age and was inversely correlated with endothelial cell density. They suggested the findings might be used as an indirect way to assess the status of the corneal endothelium.

SOURCE: Karmiris E, Soulantzou K, Machairoudia G, et al. Corneal densitometry assessed with Scheimpflug camera in healthy corneas and correlation with specular microscopy values and age. Cornea 2021; Apr 1. [Epub ahead of print].


Relationship Between Retinal Vascular Bed Area on WVF FA and DR Severity

Researchers aimed to quantify retinal vascular bed area (RVBA) in square millimeters on stereographically projected ultra-widefield (UWF) fluorescein angiography in eyes with diabetic retinopathy.

The prospective, observational study using baseline Optos 200Tx UWF FA images of 80 eyes with DR from the DAVE and RECOVERY studies were stereographically projected at the Doheny Image Reading Center in Los Angeles, to adjust for peripheral distortion. The early-phase FA frame was used to extract the retinal vasculature as a mask for calculating RVBA. The pixels of the retinal vasculature were automatically computed in square millimeters using manufacturer-provided software.

Eighteen of 80 diabetic eyes were excluded because image quality and contrast were insufficient for automatic extraction of the retinal vasculature from the background fluorescence. The remaining 62 eyes were included in the final analysis. Here are some of the findings:
• In comparison with age-matched and sex-matched normal controls:
   o DR eyes had a higher global RVBA for the entire retina (p<0.001);
   o RVBA correlated with DR severity (p<0.001), with a higher RVBA in eyes with proliferative DR (66.1 ±16.2 mm2) than in those with nonproliferative DR (56.2 ±16.6 mm2) or in normal controls (37.2 ±9.9 mm2). This tendency was also present in the posterior retina and mid-periphery but absent in the far-periphery.
   o RVBA didn’t correlate with retinal ischaemia (p>0.05).

Researchers found that DR eyes had a larger global retinal vascular bed area for the entire retina than normal controls, and that RVBA appeared to indicate DR severity. However, they noted, the biomarker wasn’t observed to be a good indicator of retinal ischemia.

SOURCE: Fan W, Uji A, Nittala M, et al. Retinal vascular bed area on ultra-wide field fluorescein angiography indicates the severity of diabetic retinopathy. Br J Ophthalmol 2021; Apr 7. [Epub ahead of print].




Industry News

Apellis Reports Data from Phase Ib Study of Pegcetacoplan

Apellis Pharmaceuticals announced 24-month data from the Phase Ib APL2-103 study of pegcetacoplan (15 mg/0.1 mL), an investigational targeted C3 therapy, in patients with advanced geographic atrophy secondary to age-related macular degeneration and low vision. The main study assessed the safety of the Phase III formulation of the drug. The current post hoc analysis, including eight patients with at least 24 months of data, revealed the growth rate of GA lesions in the treated eye was 46 percent (mean square root) slower than the untreated fellow eye (p=0.007). Read more.


TeamedOn and AGTC Advance X-Linked Retinoschisis Gene Therapy

TeamedOn International and Applied Genetic Technologies announced a licensing agreement to advance a gene therapy to treat X-linked retinoschisis. Under the terms of the agreement, AGTC will provide TeamedOn with the clinical trial material, and pre-clinical and clinical data generated to develop AGTC’s investigational intravitreal gene therapy candidate, rAAV2tYF-CB-hRS1. Read more.



ProQR Treatment Shows Benefits in Leber’s

ProQR Therapeutics announced new findings in one patient that indicate vision improvement after treatment with sepofarsen in a clinical trial for CEP290-mediated Leber’s congenital amaurosis 10 (LCA10). The patient, homozygous for the c.2991+1655A>G mutation in CEP290, was part of a larger cohort in the Phase I/II clinical trial, and was studied for 15 months after intravitreal treatment with sepofarsen. The company says that measures of visual function and retinal structure—including visual acuity, light sensitivity and visual fields—reached a substantial efficacy peak near three months after injection and remained better than baseline at 15 months. View the study.



Spark Collaborates with Senti Bio to Bolster Gene Therapy Research

Spark Therapeutics announced a collaboration and option agreement with Senti Biosciences to apply Senti Bio’s gene circuit technology to the development of gene therapies directed toward specific cell types in the eye and other areas of the body. Read more.

B+L Announces Topline Results From Phase III NOV03 Trial

Bausch + Lomb announced topline data from the first Phase III trial (GOBI trial) evaluating the investigational topical drug NOV03 (perfluorohexyloctane) aimed at treating the signs and symptoms of dry-eye disease associated with meibomian gland dysfunction. In the topline data, the drug met both of its co-primary endpoints. Read more.

Santen Teams with Mass Eye and Ear & Ulster University

Santen announced a research initiative with scientists from Massachusetts Eye and Ear and Ulster University (UK) to research and develop novel treatments for glaucoma. Read more.




Complimentary CME Education Videos



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