Elsevier

Ophthalmology

Volume 125, Issue 11, November 2018, Pages 1720-1728
Ophthalmology

Original article
Macular and Optic Nerve Head Vessel Density and Progressive Retinal Nerve Fiber Layer Loss in Glaucoma

https://doi.org/10.1016/j.ophtha.2018.05.006Get rights and content

Purpose

To investigate prospectively the relationship between macular and peripapillary vessel density and progressive retinal nerve fiber layer (RNFL) loss in patients with mild to moderate primary open-angle glaucoma.

Design

Prospective, observational study.

Participants

One hundred thirty-two eyes of 83 patients with glaucoma followed up for at least 2 years (average: 27.3±3.36 months).

Methods

Measurements of macular whole image vessel density (m-wiVD) and optic nerve head whole image vessel density (onh-wiVD) were acquired at baseline using OCT angiography. RNFL, minimum rim width (MRW), and ganglion cell plus inner plexiform layer (GCIPL) thickness were obtained semiannually using spectral-domain OCT. Random-effects models were used to investigate the relationship between baseline vessel density parameters and rates of RNFL loss after adjusting for the following confounding factors: baseline visual field mean deviation, MRW, GCIPL thickness, central corneal thickness (CCT), and mean intraocular pressure during follow-up and disc hemorrhage, with or without including baseline RNFL.

Main Outcome Measures

Effects of m-wiVD and onh-wiVD on rates of RNFL loss over time.

Results

Average baseline RNFL thickness was 79.5±14.8 μm, which declined with a mean slope of –1.07 μm/year (95% confidence interval, –1.28 to –0.85). In the univariate model, including only a predictive factor and time and their interaction, each 1% lower m-wiVD and onh-wiVD was associated with a 0.11-μm/year (P < 0.001) and 0.06-μm/year (P = 0.031) faster rate of RNFL decline, respectively. A similar relationship between low m-wiVD and onh-wiVD and faster rates of RNFL loss was found using different multivariate models. The association between vessel density measurements and rate of RNFL loss was weak (r2 = 0.125 and r2 = 0.033 for m-wiVD and onh-wiVD, respectively). Average CCT also was a predictor for faster RNFL decline in both the univariate (0.11 μm/year; P < 0.001) and multivariate models.

Conclusions

Lower baseline macular and optic nerve head (ONH) vessel density are associated with a faster rate of RNFL progression in mild to moderate glaucoma. Assessment of ONH and macular vessel density may add significant information to the evaluation of the risk of glaucoma progression and prediction of rates of disease worsening.

Section snippets

Methods

This was a longitudinal, observational cohort study including 132 eyes from 83 patients with POAG enrolled in the Diagnostic Innovations in Glaucoma Study who underwent OCTA (AngioVue; Optovue, Inc., Fremont, CA) and spectral-domain (SD) OCT ONH imaging (Heidelberg Engineering, Inc., Heidelberg, Germany). All the methods adhered to the tenets of the Declaration of Helsinki and to the Health Insurance Portability and Accountability Act. The institutional review boards at the University of

Results

After excluding poor-quality OCTA images (27 eyes) and poor-quality SD OCT images (10 eyes), 132 eyes of 83 patients (mean age, 68.7±10.4 years; mean SAP MD, –2.44±2.85 dB) were included in the analysis. Table 1 summarizes the baseline characteristics of the study participants. Average baseline m-wiVD and onh-wiVD were 50.0±3.7% and 52.4±3.7%, respectively. Average baseline RNFL thickness was 79.5±14.7 μm, which declined with a mean slope of –1.07 μm/year (95% confidence interval [CI], –1.28 to

Discussion

In this study, OCTA parameters were associated significantly with the rate of RNFL decline in patients with mild to moderate POAG followed up over time. Eyes with lower baseline m-wiVD and onh-wiVD tended to progress significantly faster than those with higher values. Such an association was present even in a multivariate model adjusting for structural parameters and factors known potentially to affect rates of glaucoma progression. These data demonstrate that vascular density parameters

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    Supplemental material available at www.aaojournal.org.

    Financial Disclosure(s): The author(s) have made the following disclosure(s): L.M.Z.: Financial support - Carl Zeiss Meditec, Heidelberg Engineering, Topcon, Optovue.

    T.S.: Financial support - Alcon.

    R.N.W.: Financial support - Carl Zeiss Meditec, Genentech, Heidelberg Engineering, Konan, Optos, Optovue, Tomey, Topcon; Consultant - Aerie Pharmaceuticals, Alcon, Allergan, Bausch & Lomb, Eyenovia, Novartis, Unity.

    Supported in part by the National Eye Institute, National Institutes of Health, Bethesda, Maryland (grant nos.: EY029058 [R.N.W.], EY011008 [L.M.Z.], EY14267 [L.M.Z.], and EY019869 [L.M.Z.]); the National Institutes of Health (core grant no.: P30EY022589); the Japan Society for the Promotion of Science (KAKENHI grant nos.: 15K21335 and 16KK0208 [T.S.]); an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York; by Alcon, Allergan, Pfizer, Merck, and Santen (grants for participants’ glaucoma medications); and by the donors of the National Glaucoma Research Program (a program of the BrightFocus Foundation).

    HUMAN SUBJECTS: This study included human subjects or tissues. Study protocol was approved by the institutional review board of the University of California, San Diego. Informed consent was obtained from all human subjects. This research complied with the Health Insurance Portability and Accountability (HIPAA) Act of 1996 and adhered to the tenets of the Declaration of Helsinki.

    No animals were used in this study.

    Author Contributions:

    Conception and design: Moghimi, Zangwill, Weinreb

    Analysis and interpretation: Moghimi, Zangwill, Penteado, Hasenstab, Ghahari, Hou, Christopher, Yarmohammadi, Manalastas, Shoji, Bowd, Weinreb

    Data collection: Moghimi, Zangwill, Penteado, Hasenstab, Ghahari, Hou, Christopher, Yarmohammadi, Manalastas, Shoji, Bowd, Weinreb

    Obtained funding: None

    Overall responsibility: Moghimi, Zangwill, Penteado, Hasenstab, Ghahari, Hou, Christopher, Yarmohammadi, Manalastas, Shoji, Bowd, Weinreb

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