Participants

This study included treatment-naïve eyes affected by IPS in consecutive patients who visited Kyoto University Hospital between January 2008 and May 2016. All eyes underwent a comprehensive ophthalmologic examination, including autorefractometry (ARK1; Nidek, Gamagori, Japan), BCVA measurements with a 5-m Landolt chart, measurement of intraocular pressure, indirect ophthalmoscopy, slit-lamp biomicroscopy with contact lens, axial length (AL) measurement using partial coherence interferometry (IOLMaster; Carl Zeiss Meditec, Dublin, California, USA), color fundus photography (TRC-NW8F; Topcon Corp, Tokyo, Japan), optical coherence tomography (OCT, Spectralis HRA+OCT, Heidelberg Engineering, Heidelberg, Germany; RS-3000 Advance, Nidek; or DRI OCT-1, Topcon), fundus fluorescein angiography, and indocyanine green angiography (Heidelberg Retina Angiography 2; Heidelberg Engineering).

Retinal specialists diagnosed IPS on the basis of fundus photography, dilated binocular indirect ophthalmoscopy, and slit-lamp biomicroscopy with contact lens. As previously reported, vertical scans of OCT were used to confirm that the border of the inferior staphyloma lay across the macula. The inclusion criterion was IPS, of which the superior edge was lying across the macula, followed for 4 years. The exclusion criteria were as follows: the absence of baseline and 4-year BCVA and OCT image; poor OCT image quality for analysis at baseline; photocoagulation or PDT for eyes without CNV during the observation period; and other baseline macular diseases, including epiretinal membrane, vitreomacular traction syndrome, diabetic retinopathy, and macular hole.

Classification

We classified eligible eyes with IPS into 3 groups on the basis of macular complications at baseline ( Figure 1 ), as previously reported ² : (1) eyes without CNV or retinal exudate including SRD or retinal pigment epithelial detachment (no-exudate group), (2) eyes without CNV and with retinal exudate (exudate group), and (3) eyes with CNV (CNV group). We carefully determined the presence or absence of CNV on the basis of OCT, fluorescein angiography, and indocyanine green angiography findings. We performed pro re nata (PRN) intravitreal anti-VEGF agent injections (Eylea, Bayer, Basel, Switzerland; Lucentis, Novartis, Basel, Switzerland) in eyes with exudate in the CNV group. When the poor effectiveness of anti-VEGF therapy was confirmed, we performed additional PDT. In the no-exudate and exudate groups, we confirmed CNV development in the 4-year observation period.

Representative vertical-scan optical coherence images used for classification based on macular complication. Eligible eyes with inferior posterior staphyloma were classified into 3 groups based on macular complication at baseline. (Top) No-exudate group. Eyes without choroidal neovascularization (CNV) or retinal exudate of subretinal detachment or retinal pigment epithelial detachment. (Middle) Exudate group. Eyes without CNV and with retinal exudate. (Bottom) CNV group. Eyes with CNV.

Analysis of OCT Images and Color Fundus Photography Images

We measured the central retinal thickness (CRT), central choroidal thickness (CCT), subretinal fluid (SRF) height at the foveal center, and the distance between the upper border of the IPS and fovea (defined as “border-fovea distance”) on a vertical-scan OCT image through the fovea using the built-in software. We defined CRT as the distance between the vitreoretinal surface and the outer surface of the RPE. We defined CCT as the distance between the outer surface of Bruch’s membrane and the chorioscleral interface. We defined SRF height as the distance between the outer surface of the sensory retina and the inner surface of RPE. In addition, we defined the border-fovea distance as the distance between the inner surface of the RPE at the fovea and that at the upper border, which we defined as the thinnest point of the choroid ( Figure 2 ) because previous studies showed that eyes with IPS often have a belt-shaped area with the thinnest choroid being at the superior border of the staphyloma. ^, Positive values of the border-fovea distance demonstrated that the fovea lies superior to the border. We confirmed tilted disc on the basis of color fundus photography images.

Measurement of the border-fovea distance. We defined the distance between the upper border of the staphyloma and fovea as the border-fovea distance. It was measured as the distance between the inner surface of the retinal pigment epithelium at the fovea (the right arrowhead) and that at the upper border, which was defined as the thinnest point of the choroid (left arrowhead) on a vertical-scan OCT image through the fovea using built-in software.

Statistical Analysis

As applicable, we presented all data as mean ± standard deviation or number of eyes. We converted all BCVA values into the logarithm of the minimum angle of resolution (logMAR) values for statistical analysis. Among the 3 groups, we performed comparison analyses using 1-way analysis of variance and subsequent pairwise comparisons and χ ² trend test where applicable. Using repeated measures analysis of variance in each group, we analyzed the change in logMAR BCVA values in 4 years (baseline, 6-month, 1-year, 2-year, 3-year, and 4-year BCVA values). Using Spearman’s correlation coefficient, we performed univariate correlation analyses between the 4-year logMAR BCVA and baseline or treatment-associated parameters; and between the 4-year change in logMAR BCVA and those parameters. Multivariate correlation analyses were performed using the 4-year logMAR BCVA or 4-year change in logMAR BCVA as the dependent variable and baseline or treatment-associated parameters with P values <.20 on Spearman’s correlation test as independent variables. We conducted all statistical analyses using SPSS version 27 software (IBM Corp, Armonk, New York, USA).