ORIGINAL STUDY

Rates and Patterns of Macular and Circumpapillary Retinal Nerve Fiber Layer Thinning in Preperimetric and Perimetric Glaucomatous Eyes Jung Hwa Na, MD,*w Kyung Rim Sung, MD, PhD,* Seung Hee Baek, PhD,z Soon Tae Kim, BS,* Kilwhan Shon, MD,* and Jong Jin Jung, MDw

Purpose: To evaluate and compare the rates and patterns of macular and circumpapillary retinal nerve fiber layer (cRNFL) thickness thinning, assessed by spectral-domain optical coherence tomography (Cirrus SD-OCT), in eyes with preperimetric (PPG) and perimetric glaucoma (PG). Methods: The present retrospective cohort study included 127 eyes of 75 patients (PPG, 87; PG, 40) with a mean follow-up of 2.53 years. All patients underwent at least 4 SD-OCT examinations. Linear mixed effects models were used to evaluate the rates of changes in relevant cRNFL and macular parameters. Results: Overall, after adjusting for covariates including age, baseline OCT data, and visual field severity, thickness changes in the 6 o’clock ( 2.325 mm/y, cRNFL) and inferior outer sector (2.879 mm/y, macular) showed the highest progression rates among all evaluated parameters. When  0.26 and 0.42 mm/y in average cRNFL and macular thickness changes were used as reference values for age-related physiological loss, 64.4% and 80.5% of PPG eyes and 60% and 70% of PG eyes, respectively, showed higher progression rates than these values. PG eyes showed significantly higher progression rates in the fovea and the inferior inner sector of the macula than did PPG eyes, although no progression rate of any cRNFL parameter differed between the 2 groups. Conclusions: PG and PPG eyes showed different rates and patterns in macular thickness progression when assessed by Cirrus SDOCT. Key Words: glaucoma, OCT, retinal nerve fiber layer, macular, progression

(J Glaucoma 2015;24:278–285)

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laucoma is characterized by progressive optic neuropathy accompanied by development of a typical visual field (VF) defect.1–4 In patients who are suspected of having glaucoma, but who are in the preperimetric stage, in other words, in the stage of no apparent abnormality in standard automated perimetry (SAP), detection of progression Received for publication November 8, 2011; accepted June 7, 2012. From the Departments of *Ophthalmology; zClinical Epidemiology and Biostatistics, Asan Medical Center, College of Medicine, University of Ulsan; and wDepartment of Ophthalmology, Kim’s Eye Hospital, Myung-Gok Eye Research Institute, Konyang University, Seoul, Korea. Disclosure: The authors declare no conflict of interest. Reprints: Kyung Rim Sung, MD, PhD, Department of Ophthalmology, Asan Medical Center, College of Medicine, University of Ulsan, 388-1 Pungnap-2-dong, Songpa-gu, Seoul 138-736, Korea (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/IJG.0000000000000046

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allows confirmation of glaucoma diagnosis. In patients already showing perimetric changes, evidence of progression can help to determine whether more aggressive management should be commenced to halt disease aggravation. Therefore, detection of progression is of paramount importance in terms of the care of both preperimetric (PPG) and perimetric glaucoma (PG) patients. VF examinations, particularly SAP, have served as reference standards for assessment of glaucoma progression and many clinical trials evaluated glaucoma development in this manner.5–8 However, it has been reported that a proportion of glaucomatous eyes show structural changes in only the retinal nerve fiber layer (RNFL) and/or optic nerve head, without any apparent defect in visual function.9–13 Moreover, structural change can precede development of a functional SAP deficit when glaucomatous damage occurs, emphasizing the importance of the use of structural measures to afford earlier detection.11,12,14 Therefore, detection of progression by structural assessment is becoming increasingly important. Optical coherence tomography (OCT) is reliable when used to detect glaucoma and has been widely used for structural evaluation of glaucomatous eyes.15–23 In addition, some reports have indicated that OCT can be useful to monitor eyes showing glaucomatous progression.24–32 The recent introduction of spectral-domain OCT (SD-OCT) facilitates retinal imaging at higher resolution and using a faster scan speed.33 RNFL measurement using the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA), a commercially available SD-OCT platform, yielded repeatable and reproducible results, and afforded a better diagnostic performance than did an earlier time-domain OCT platform, the Stratus OCT.34–36 As might be expected, Cirrus HDOCT outperformed Stratus-OCT in the sense that the former platform detected more eyes exhibiting RNFL progression, and the agreement of such data with VF progression was also better when the Cirrus-OCT was used.30 Evaluation of changes over time in structural parameters is essential to identify glaucoma progression. In the present study, we intended to investigate the structural progression of glaucomatous eyes using SD-OCT. Hence, we measured and compared the rates of circumpapillary RNFL (cRNFL) and macular thickness reduction using SD-OCT (Cirrus HD-OCT) in eyes with PPG and PG. In addition, we analyzed the patterns of cRNFL and macular thinning in both PPG and PG eyes.

METHODS Subjects Patients evaluated from September 2008 to July 2011 by 1 glaucoma specialist (K.R.S.) at the glaucoma clinic of J Glaucoma



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Volume 24, Number 4, April/May 2015

the Asan Medical Center, Seoul, Korea, and who met inclusion criteria, were consecutively included through retrospective medical record review. At initial testing, each participant received a comprehensive ophthalmologic examination including a review of medical history, measurement of best-corrected visual acuity, slit-lamp biomicroscopy, Goldmann applanation tonometry, gonioscopy, dilated fundoscopic examination using a 90 or 78 D lens, stereoscopic optic disc photography, RNFL photography, a VF test (Humphrey field analyzer, Swedish Interactive Threshold Algorithm 24-2; Carl Zeiss Meditec), and Cirrus HD-OCT. For inclusion, all participants had to meet the following criteria: best-corrected visual acuity of 20/40 or better, with a spherical refractive error between 6.0 and + 4.0 D and a cylinder correction within + 3 D; and presence of a normal anterior chamber and open-angle on slit-lamp and gonioscopic examinations. Stereoscopic optic disc and RNFL photography were reviewed by 2 glaucoma specialists (K.R.S. and J.H.N.). Our present study included patients with glaucomatous optic nerve heads, showing enlarged cupping, diffuse or focal neural rim thinning, disc hemorrhage, or RNFL defects that were confirmed and agreed upon by 2 glaucoma specialists (K.R.S. and J.H.N.). We divided all subjects into 2 subgroups; those with PG or PPG. The PG subgroup included those showing glaucomatous VF defects as confirmed by the conduct of at least 2 initial reliable VF examinations. Glaucomatous VF defects were defined as a cluster of 3 points with probabilities of

Rates and patterns of macular and circumpapillary retinal nerve fiber layer thinning in preperimetric and perimetric glaucomatous eyes.

To evaluate and compare the rates and patterns of macular and circumpapillary retinal nerve fiber layer (cRNFL) thickness thinning, assessed by spectr...
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