To report the clinical findings of the patients with retinal pigment epithelium (RPE) aperture secondary to age-related macular degeneration (AMD).
A retrospective data analysis was conducted of patients at the University of Tokyo Hospital eye clinic, from the year September 1st, 2012 to 2019. Review of the medical records of patients with RPE aperture accompanied by AMD was performed. We investigated age, best-corrected visual acuity (BCVA), images of spectral domain optical coherence tomography, short-wave fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography, and retinal sensitivity measured with microperimetry. The change in visual acuity or the area of the aperture during the follow-up period was analyzed.
Five eyes of 5 patients (4 men, one woman) were included in the analysis. The mean age at presentation was 78.6 ± 9.1 years. The average length of follow-up was 23.6 ± 17.9 months. The RPE apertures appeared as round, either at the apex or at the base of PED, with no evidence of accompanying CNV but subretinal detachment (SRD) above the aperture. On FAF, the apertures appeared as sharply demarcated round areas of hypoautofluorescence. The FA revealed sharply demarcated round areas of window defects in the early and mid-phase with leakage in the late phase corresponding to SRD. The area of apertures enlarged during the follow-up period. Mean BCVA got worse from 0.20 logMAR at the initial presentation to 0.39 logMAR at the last visit. The retinal sensitivity was reduced but partly preserved above the area of aperture.
Conclusions and importance
RPE aperture was found in some patients with drusenoid PED secondary to AMD. It enlarged during follow-up. Visual acuity was declined. Retinal sensitivity was decreased but partly preserved.
Retinal pigment epithelium detachment (PED) is a prominent feature of many chorio-retinal disease processes, including central serous chorioretinopathy (CSC), inflammatory, neoplastic, iatrogenic etiologies, and neovascular/nonneovascular age-related macular degeneration (AMD). Longstanding PEDs cause thinning in the RPE on OCT, lead to unexpected complications during follow-up. Patients with PED from nonneovascular or dry form of AMD shows relatively more favorable prognosis than those with neovascular AMD. PEDs with CNV may develop retinal pigment epithelium (RPE) tears, typically at the edge of attached and detached RPE, where the PED is most vulnerable to hydrostatic forces. RPE tears result in loss of photoreceptors with the development of fibrous tissue and enlargement of the RPE defects, leading to remarkable decrease of visual acuity.
Recently, RPE aperture was reported as a new finding associated with PED. RPE aperture was characterized by round RPE defect accompanying with PED. It was found in several diseases including AMD, adult-onset foveomacular vitelliform dystrophy, and chronic central serous chorioretinopathy. RPE aperture in AMD should be distinguished by typical RPE tears and thought to develop in the evolution of nonneovascular AMD. There have been few reports on RPE aperture, making the demography or pathogenesis of this finding still unclear. Additionally, retinal function other than visual acuity has not been reported to the best of our knowledge. Herein, we reported the clinical characteristics of Asian patients with RPE aperture associated with AMD, and analyzed in some subjects their retinal function evaluated with fundus microperimetry.
Materials and methods
A retrospective data analysis was conducted of patients at the University of Tokyo Hospital eye clinic, from the year September 1st, 2012 to 2019. Review of the medical records of 5 eyes of 5 patients with RPE aperture associated with AMD was performed. All patients underwent a complete ophthalmologic examination routinely in every 2-month visits, including best-corrected visual acuity (BCVA), color fundus photography, dilated ophthalmoscopy, spectral domain optical coherence tomography (SD-OCT, Spectralis R , Heidelberg Engineering, Heidelberg, Germany). Fundus autofluorescent imaging using a short-wavelength (SW-AF; 488 nm) light source (Spectralis HRA R , Heidelberg Engineering, Heidelberg, Germany). Indocyanine-green angiography (ICGA) and fluorescein angiography (FA) were performed using Spectralis R HRA. In some patients, retinal sensitivity was measured with fundus-monitoring microperimetry (MP-3 R , Nidek Co, Japan) , in 2019. In contrast to conventional perimetry, microperimetry utilizes fundus imaging and motion tracking to ensure precise stimulation of a certain location of the retina. The MP-3 measurement was based on a 4–2 full threshold staircase strategy. The stimulus dynamic range was between 0 and 34 dB. Twenty-five stimulus points were examined, covering 8°. Measurements were performed using the standard Goldmann III stimulus size. After completion of sensitivity testing, a color fundus image with the superimposed sensitivity values was exported from the device. Mean sensitivity values at the total area, the aperture area, and the non-aperture area were calculated.
An 81-year-old woman presented with decreased vision in her both eyes. Her diagnosis of the referring doctor was drusenoid PED. She had received 12 times of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy (3 ranibizumab, 9 aflibercept) before the referral to our clinic. The BCVA was 0.30 logMAR in her both eyes at initial visit to our clinic. The fundus showed grayish-white drusenoid PED at the center of the macula ( Fig. 1 a). Microperimetry testing showed that an aperture area had a decreased sensitivity ( Fig. 1 b). The OCT scans revealed PEDs with SRD, and apertures were seen in the right eye ( Fig. 1 c and d). We found the loss of external limiting membrane accompanied by outer retinal thinning, ellipsoid or interdigitation zone loss in some areas above the PED. FA and ICGA showed no evidence of any CNV ( Fig. 1 e and f). FAF showed sharply demarcated round apertures ( Fig. 1 g). Her VA declined to 0.52 logMAR at the last visit.
A 79-year-old men presented complaining of poor vision in both eyes. He was diagnosed as drusenoid PED secondary to AMD by the referring doctor. His BCVA in both eyes were 0.22 logMAR at initial visit. OCT showed a PED and an aperture in his left eye, no any SRDs ( Fig. 2 a). Microperimetry testing showed that an aperture area had a decreased sensitivity ( Fig. 2 b). FA (03:34) showed no evidence of CNV ( Fig. 2 c). FAF showed multiple hyperautofluorescent spots at the site of the PED ( Fig. 2 d). The patient received 3 times of anti-VEGF therapy (aflibercept). His VA was 0.52 logMAR at the last visit.
An 89-year-old men presented with decreased vision in his left eye. His diagnosis of the referring doctor was drusenoid PED. The BCVA was 0.30 logMAR in his left eye at his first visit. FA and ICGA showed no evidence of any CNV. The SD-OCT revealed the RPE aperture with SRD. The BCVA dropped to 0.52 logMAR at the last visit.
An 84-year-old men, noted a visual acuity decrease in the left eye. His diagnosis of the referring doctor was drusenoid PED.BCVA was 0.05 logMAR at first visit in his left eye, and SD-OCT revealed a central RPE-defect, SRF. FA and ICGA showed no definite evidence of a CNV.
A 64-year-old men had decreased vision in his right eye and distortion. He was diagnosed as drusenoid PED secondary to AMD by the referring doctor. The BCVA was 0.15 at first visit in his right eye. FA and ICGA showed no evidence of any CNV, OCT showed the aperture.
In the present study, RPE apertures were identified in 5 eyes of 5 patients (4 men, one woman). All patients were Japanese. Clinical characteristics of 5 patients are shown in Table 1 . Mean age was 78.6 ± 9.1 years at presentation, Mean BCVA at presentation was 0.20 ± 0.11 logMAR.
|Case#||Age (years)||Gender||Follow-up period in our clinic (months)||IVT number of Anti-VEGF in our clinic||Findings in the Fellow eye|
|1||81||F||16||1* (aflibercept 1)||drusenoid PED|
|2||79||M||18||3 (aflibercept 3)||drusen|
|3||89||M||55||6 (ranibizumab 2) |
|4||84||M||19||3 (aflibercept 3)||fibrotic scar|
|Average||78.6 ± 9.1||20.4 ± 9.2||2.6 ± 2.3|