ORIGINAL STUDY
Development of Glaucomatous Visual Field Defects in Preperimetric Glaucoma Patients Within 3 Years of Diagnosis Hiroko Inuzuka, MD,*w Kazuhide Kawase, MD, PhD,* Akira Sawada, MD, PhD,* Satoko Kokuzawa, MD,* Kyoko Ishida, MD, PhD,* and Tetsuya Yamamoto, MD, PhD*
Purpose: To determine the characteristics of eyes diagnosed with preperimetric glaucoma (PPG) that developed glaucomatous visual field defects (VFDs) within 3 years of the diagnosis. Patients and Methods: The medical charts of 77 eyes of 77 patients with PPG were reviewed. An eye was diagnosed with PPG when there was neuroretinal rim thinning, cupping of the optic disc, or a suspicious retinal nerve fiber layer (RNFL) defect, and had no conditions fulfilling Anderson’s criteria for glaucoma. The Central 30-2 SITA-Standard program of the Humphrey Field Analyzer was used to determine the presence of VFDs and the thicknesses of the retinal layers was determined by spectral-domain optical coherence tomography. Results: Ten of the 77 patients with PPG (13.0%) developed glaucomatous VFD. These 10 eyes had significantly thinner macular ganglion cell and inner plexiform layer (mGCIPL) thickness in the inferior and inferotemporal sectors, and also the circumpapillary retinal nerve fiber layer (cpRNFL) thickness at the 7 or 8 o’clock sectors. In the 3 years post-PPG period, these eyes had significant decreases in the mGCIPL thickness of all the inferior sectors, and cpRNFL at the 7 or 8 o’clock sectors. The mean intraocular pressure in eyes with VFDs (15.2 ± 2.0 mm Hg) was significantly higher than that in those without VFDs (13.5 ± 2.6 mm Hg; P = 0.042). Conclusions: Significant structural changes were observed in the mGCIPL and cpRNFL at PPG diagnosis, before the development of a VFDs. Close monitoring of intraocular pressure is essential for the appropriate management of PPG. Key Words: macular ganglion cell-inner plexiform layer, circumpapillary retinal nerve fiber layer, preperimetric glaucoma, spectraldomain optical coherence tomography
(J Glaucoma 2016;25:e591–e595)
I
t is well known that in eyes with glaucoma, a decrease in the circumpapillary retinal nerve fiber layer (cpRNFL) thickness precedes the onset of visual field defects (VFDs).1–3 Thus, assessments of the cpRNFL thickness by spectral-domain optical coherence tomography (SD-OCT) Received for publication April 16, 2014; accepted March 25, 2015. From the *Department of Ophthalmology, Gifu University Graduate School of Medicine; and wDepartment of Ophthalmology, Gifu Municipal Hospital, Gifu, Japan. Disclosure: The authors declare no conflict of interest. Reprints: Hiroko Inuzuka, MD, Department of Ophthalmology, Gifu University Graduate School of Medicine, 1-1, Yanagido, Gifu 5011194, Japan (e-mail: [email protected]). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/IJG.0000000000000260
J Glaucoma
Volume 25, Number 6, June 2016
can enhance the diagnosis of glaucoma especially in eyes suspected of having glaucoma.4 Approximately 50% of the retinal ganglion cells are located in the macular area,5 and measurements of the macular thickness can help in the detection of glaucomatous eyes. Tan et al6 reported that glaucoma leads to a thinning of the macular retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer even before a VFD can be detected. Thus, assessments of the 3 innermost retinal layers appear to lead to optimal glaucoma detection. Improved methods of peripheral macular sampling using new OCT scan patterns has further improved the diagnostic ability of OCT.6 In addition, Nakano et al7 reported that speckle noisereduced SD-OCT could obtain better images and measurements of the macular GCL thicknesses which is severely thinned even in eyes with preperimetric glaucoma (PPG). Although the macular changes have been thought to occur in the later stages of glaucoma, the advent of OCT has permitted the detection of changes in the macular GCL and RNFL much earlier in eyes with glaucoma.8 In fact, both the cpRNFL thickness and macular volume were shown to decrease even in the early stages of glaucoma.9 Moreover, several reports have demonstrated that the combined thicknesses of the macular GCL and IPL (mGCIPL) and the cpRNFL had similar power in diagnosing early glaucoma or PPG.10–14 However, the chronological changes of the macular and papillary structures in eyes with PPG and the characteristics of the eyes at the time of diagnosis of PPG that will later develop VFDs remain poorly understood. Therefore, the purpose of this study was to analyze the thicknesses of both the mGCIPL and cpRNFL within a 3-year period post-PPG diagnosis and to compare the clinical findings of patients who did or did not develop the VFDs.
PATIENTS AND METHODS This study was approved by the Ethics Committee of Gifu University Graduate School of Medicine. A review of patient charts was conducted at the Department of Ophthalmology, Gifu University Hospital, Gifu, Japan. The inclusion criteria were: (1) presence of PPG; (2) primary open-angle glaucoma (POAG) or normal-tension glaucoma (NTG); (3) best-corrected visual acuity of at least 20/25; (4) refractive error (spherical equivalent) between 6.0 and + 6.0 D; (5) absence of any ophthalmological diseases that might have affected the reliability of the perimetric examinations or acquisition of clear OCT images (with the exception of incipient cataracts and glaucoma/PPG in the www.glaucomajournal.com |
Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
e591
Inuzuka et al
J Glaucoma
TABLE 1. Patient Characteristics at PPG Diagnosis
Case (n)
77 Cases 77 Eyes
Sex (men/women) Age (y) Refractive error (D) IOP (mm Hg) MD (dB) PSD (dB)
39/38 56.5 ± 12.1 (33 to 81) 2.53 ± 2.34 ( 6.00 to + 1.75) 14.1 ± 2.6 (7 to 20) + 0.74 ± 0.89 ( 1.96 to + 2.65) 1.77 ± 0.31 (1.25 to 2.85)
IOP indicates intraocular pressure; PPG, preperimetric glaucoma; PSD, pattern SD.
contralateral eye); (6) intraocular pressure (IOP) controlled with/without glaucoma medication and without surgical intervention; (7) follow-up period after the PPG diagnosis of at least 3 years; and (8) periodic Humphrey Field Analyzer (HFA) program Central 30-2 SITA-Standard (Carl Zeiss Meditec, Dublin, CA) and OCT evaluations. We selected 77 eyes with PPG from 5400 consecutive cases that had been examined by OCT. Seventeen eyes were diagnosed with POAG and 60 eyes with NTG. We defined an eye as PPG by the presence of an optic disc with neuroretinal rim thinning, cupping, or a suspicious RNFL defect, and with the absence of any conditions fulfilling Anderson’s criteria of glaucomatous VFDs. A glaucomatous VFD was defined as 3 consecutive points with P < 5% and with 1 point P < 1% among the pattern deviation measurements of the HFA Central 30-2 SITAStandard program. The participants were selected independently by 2 experienced graders. We used the HFA program Central 30-2 SITA-Standard and graded the cases as follows: no point at P < 0.5%, 0 case; no point at 0.5rP < 1%, 0 case; and
Development of Glaucomatous Visual Field Defects in Preperimetric Glaucoma Patients Within 3 Years of Diagnosis Hiroko Inuzuka, MD,*w Kazuhide Kawase, MD, PhD,* Akira Sawada, MD, PhD,* Satoko Kokuzawa, MD,* Kyoko Ishida, MD, PhD,* and Tetsuya Yamamoto, MD, PhD*
Purpose: To determine the characteristics of eyes diagnosed with preperimetric glaucoma (PPG) that developed glaucomatous visual field defects (VFDs) within 3 years of the diagnosis. Patients and Methods: The medical charts of 77 eyes of 77 patients with PPG were reviewed. An eye was diagnosed with PPG when there was neuroretinal rim thinning, cupping of the optic disc, or a suspicious retinal nerve fiber layer (RNFL) defect, and had no conditions fulfilling Anderson’s criteria for glaucoma. The Central 30-2 SITA-Standard program of the Humphrey Field Analyzer was used to determine the presence of VFDs and the thicknesses of the retinal layers was determined by spectral-domain optical coherence tomography. Results: Ten of the 77 patients with PPG (13.0%) developed glaucomatous VFD. These 10 eyes had significantly thinner macular ganglion cell and inner plexiform layer (mGCIPL) thickness in the inferior and inferotemporal sectors, and also the circumpapillary retinal nerve fiber layer (cpRNFL) thickness at the 7 or 8 o’clock sectors. In the 3 years post-PPG period, these eyes had significant decreases in the mGCIPL thickness of all the inferior sectors, and cpRNFL at the 7 or 8 o’clock sectors. The mean intraocular pressure in eyes with VFDs (15.2 ± 2.0 mm Hg) was significantly higher than that in those without VFDs (13.5 ± 2.6 mm Hg; P = 0.042). Conclusions: Significant structural changes were observed in the mGCIPL and cpRNFL at PPG diagnosis, before the development of a VFDs. Close monitoring of intraocular pressure is essential for the appropriate management of PPG. Key Words: macular ganglion cell-inner plexiform layer, circumpapillary retinal nerve fiber layer, preperimetric glaucoma, spectraldomain optical coherence tomography
(J Glaucoma 2016;25:e591–e595)
I
t is well known that in eyes with glaucoma, a decrease in the circumpapillary retinal nerve fiber layer (cpRNFL) thickness precedes the onset of visual field defects (VFDs).1–3 Thus, assessments of the cpRNFL thickness by spectral-domain optical coherence tomography (SD-OCT) Received for publication April 16, 2014; accepted March 25, 2015. From the *Department of Ophthalmology, Gifu University Graduate School of Medicine; and wDepartment of Ophthalmology, Gifu Municipal Hospital, Gifu, Japan. Disclosure: The authors declare no conflict of interest. Reprints: Hiroko Inuzuka, MD, Department of Ophthalmology, Gifu University Graduate School of Medicine, 1-1, Yanagido, Gifu 5011194, Japan (e-mail: [email protected]). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/IJG.0000000000000260
J Glaucoma
Volume 25, Number 6, June 2016
can enhance the diagnosis of glaucoma especially in eyes suspected of having glaucoma.4 Approximately 50% of the retinal ganglion cells are located in the macular area,5 and measurements of the macular thickness can help in the detection of glaucomatous eyes. Tan et al6 reported that glaucoma leads to a thinning of the macular retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer even before a VFD can be detected. Thus, assessments of the 3 innermost retinal layers appear to lead to optimal glaucoma detection. Improved methods of peripheral macular sampling using new OCT scan patterns has further improved the diagnostic ability of OCT.6 In addition, Nakano et al7 reported that speckle noisereduced SD-OCT could obtain better images and measurements of the macular GCL thicknesses which is severely thinned even in eyes with preperimetric glaucoma (PPG). Although the macular changes have been thought to occur in the later stages of glaucoma, the advent of OCT has permitted the detection of changes in the macular GCL and RNFL much earlier in eyes with glaucoma.8 In fact, both the cpRNFL thickness and macular volume were shown to decrease even in the early stages of glaucoma.9 Moreover, several reports have demonstrated that the combined thicknesses of the macular GCL and IPL (mGCIPL) and the cpRNFL had similar power in diagnosing early glaucoma or PPG.10–14 However, the chronological changes of the macular and papillary structures in eyes with PPG and the characteristics of the eyes at the time of diagnosis of PPG that will later develop VFDs remain poorly understood. Therefore, the purpose of this study was to analyze the thicknesses of both the mGCIPL and cpRNFL within a 3-year period post-PPG diagnosis and to compare the clinical findings of patients who did or did not develop the VFDs.
PATIENTS AND METHODS This study was approved by the Ethics Committee of Gifu University Graduate School of Medicine. A review of patient charts was conducted at the Department of Ophthalmology, Gifu University Hospital, Gifu, Japan. The inclusion criteria were: (1) presence of PPG; (2) primary open-angle glaucoma (POAG) or normal-tension glaucoma (NTG); (3) best-corrected visual acuity of at least 20/25; (4) refractive error (spherical equivalent) between 6.0 and + 6.0 D; (5) absence of any ophthalmological diseases that might have affected the reliability of the perimetric examinations or acquisition of clear OCT images (with the exception of incipient cataracts and glaucoma/PPG in the www.glaucomajournal.com |
Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
e591
Inuzuka et al
J Glaucoma
TABLE 1. Patient Characteristics at PPG Diagnosis
Case (n)
77 Cases 77 Eyes
Sex (men/women) Age (y) Refractive error (D) IOP (mm Hg) MD (dB) PSD (dB)
39/38 56.5 ± 12.1 (33 to 81) 2.53 ± 2.34 ( 6.00 to + 1.75) 14.1 ± 2.6 (7 to 20) + 0.74 ± 0.89 ( 1.96 to + 2.65) 1.77 ± 0.31 (1.25 to 2.85)
IOP indicates intraocular pressure; PPG, preperimetric glaucoma; PSD, pattern SD.
contralateral eye); (6) intraocular pressure (IOP) controlled with/without glaucoma medication and without surgical intervention; (7) follow-up period after the PPG diagnosis of at least 3 years; and (8) periodic Humphrey Field Analyzer (HFA) program Central 30-2 SITA-Standard (Carl Zeiss Meditec, Dublin, CA) and OCT evaluations. We selected 77 eyes with PPG from 5400 consecutive cases that had been examined by OCT. Seventeen eyes were diagnosed with POAG and 60 eyes with NTG. We defined an eye as PPG by the presence of an optic disc with neuroretinal rim thinning, cupping, or a suspicious RNFL defect, and with the absence of any conditions fulfilling Anderson’s criteria of glaucomatous VFDs. A glaucomatous VFD was defined as 3 consecutive points with P < 5% and with 1 point P < 1% among the pattern deviation measurements of the HFA Central 30-2 SITAStandard program. The participants were selected independently by 2 experienced graders. We used the HFA program Central 30-2 SITA-Standard and graded the cases as follows: no point at P < 0.5%, 0 case; no point at 0.5rP < 1%, 0 case; and
