RPE disruption and hyper-transmission are early signs of secondary CNV with punctate inner choroidopathy in structure-OCT

Seventeen patients (18 eyes) with PIC who complained acute blurring of vision within 4 weeks from Xiamen Eye Center from April 2019 to April 2020 were included in the prospective study. The inclusion criteria were as follows: (1) Presence of one or several yellow, white or gray spots (diameter most ≤ 500μm) mostly limited to the posterior pole at the level of retinal pigment epithelium (RPE) and inner choroid with minimal vitreous reaction; (2) SD-OCT imaging revealed lesions at the level of the deep retina and choroid; (3) SD-OCTA showed no evidence of CNV. Exclusion criteria were as follows: (1) Eye diseases such as retinal vascular occlusion, diabetic retinopathy, age-related macular degeneration, optic nerve diseases, and glaucoma that affect vision; (2) Any other type of CNV; (3) After any treatment such as anti-VEGF, glucocorticoid; (4) Other white dot syndromes, such as diffuse subretinal fibrosis, acute posterior multifocal placoid pigment epitheliopathy, serpiginous choroiditis. This study was conducted under the tenets of the Declaration of Helsinki and was approved by the ethics board of Xiamen University affiliated Xiamen Eye Center, Xiamen, China. Written informed consent was obtained from all patients. All patients provided informed consent after a thorough description of the nature and consequences of the study.

Each patient underwent best corrected visual acuity (BCVA) measurement using a Snellen chart, and BCVA was then converted to logarithmic minimal angle of resolution (logMAR) units for statistical analysis. Slit lamp was used to check the anterior chamber. Dilated fundoscopy, fundus photography (KOWA nonmyd WX3D, Optos 200Tx) were applied to examine the retina. SD-OCT (Heidelberg Engineering, Heidelberg, Germany) was performed on the PIC eyes with enhanced depth imaging (EDI) and eye tracking function using a line scan, volume scan modes, which were across macular fovea and cover lesions. Enhanced depth imaging mode with deeper signal penetration providing enhanced identification of the choroidal vascular layers, and choroid sclera junction. The SD-OCT scanning protocol consisted of an A-scan through the center of the macula with a length between 8.8 mm and 10.0 mm in the horizontal and vertical direction and 19 B-scans covering an area of 20°×15.0° centered on the fovea with a scanning depth of 1.9mm. SD-OCTA (Cirrus HD-5000, Carl Zeiss, Germany) was performed in a 3 mm × 3 mm macular cube centered on the fovea and a 6 mm × 6 mm HD macular cube to encompass the lesions. Image analysis was performed by automated segmentation derived from the machine software with manual adjustments. OCTA images were acquired at the choroid, choriocapillaris, outer retina, deep capillary plexus, and superficial capillary plexus layers. Morphological characteristics including the presence of choroidal hyper-transmission, choroidal hypo-transmission, the RPE intact or disruption, and the ellipsoid zone (EZ) intact, partially continuous, or absent. These morphological characteristics were checked and compared at each visit. Patients with/without any morphological characteristic were classified into two groups. The changes of each morphological characteristic were observed and recorded at baseline, 4, 8 and 12 weeks, respectively. All of the patients were all preliminarily diagnosed as PIC without CNV at baseline as confirmed by OCTA. The occurrence of CNV was detected and confirmed by OCTA at each visit. In addition, the incidence of PIC+CNV was calculated for each patient if there is one or more morphological characteristics. The associations between morphological characteristics and CNV were analyzed. Two reviewers (CYR and LMH) separately assessed the images. Discrepancies in their findings were referred to a fundus specialist for a final determination.

Statistical analyses were conducted using IBM SPSS Statistics version 21.0 (IBM Corp., Armonk, NY, USA). Normality of the variables was examined by Shapiro-Wilk normality test. The age, refractive error, and VA were normalized (P=0.278, P=0.243, P=0.401). The measurement data were expressed as Mean ± Standard Deviation; the enumeration data were expressed as a constituent count or percentage. The rate of each morphological sign on OCT and the incidence of PIC+CNV was compared by Fisher’s exact test, respectively. A P value of < 0.05 was considered statistically significant.

A total of 17 patients (18 eyes) with PIC who complained of acute blurring of vision within 4 weeks were enrolled in the study. The mean age was 31.89±9.19 years old (ranging from 18 to 53 years old). Eleven (61.1%) of them were female. The mean refractive error was -10.47±4.38 diopter (ranging from -2.00D to -18.00D). The best corrected visual acuity (Log MAR) at baseline was 0.69±0.33. Choroidal neovascularization confirmed by SD-OCTA was developed in 5 eyes (27.8%) during follow-up. Thirteen (72.2%) patients without any evidence of CNV throughout the time of observation required no therapeutic intervention, as their inflammatory lesions resolved and their visual acuity improved; at the last visit, the average visual acuity was 0.31±0.20. All the patients with CNV received vascular endothelial growth factor inhibitor (anti-VEGF) treatment, and the CNV lesions resolved following with improved vision acuity.

A 26-year-old female complained of vision loss and metamorphopsia of her left eye with five days of evolution. The refraction was -7.25 D in both eyes. The best-corrected visual acuity (BCVA) in the right eye (RE) was 20/20 (6/6 in Snellen visual acuity of 6 meters) and in the left eye (LE) was 20/40 (6/12 in Snellen visual acuity of 6 meters). There were no signs of inflammation in the anterior chamber or vitreous cavity. Fundoscopy showed sporadic, small, round, yellow-white spots limited to the posterior pole of the left eye and revealed no hemorrhage (Fig. 1a). SD-OCT scanned the retinal white lesions in the temporal fovea and showed the presence of focal elevation of the EZ band with underlying hyper-reflective material. RPE and BM were integral and neither choroidal hyper-transmission nor hypo-transmission was observed below the lesion (Fig. 1b). No sign of CNV was found using OCTA (Fig. 1c, 1d, 1e). We diagnosed the patient with punctate inner choroidopathy without CNV, and regular follow-up visits were scheduled. Twelve weeks later, SD-OCT showed hyper-reflective material under EZ shrunk and choroid maintained normal transmission (Fig. 1f-1g). OCTA showed no neovascularization. (Fig. 1h-1j). Her visual acuity was 20/25 (6/7.5 in Snellen visual acuity of 6 meters), and the blurred vision was alleviated without therapeutic intervention.

A 22-year-old breast feeding woman was referred to our hospital with the complaint of metamorphopsia for two days in her right eye. She had myopia (-5.5 D) in both eyes. At the initial visit, her best-corrected visual acuity (BCVA) was 20/50 (6/15 in Snellen visual acuity of 6 meters) in the right eye and was 20/20 (6/6 in Snellen visual acuity of 6 meters) in the left eye. No remarkable changes were revealed in either ocular anterior segment by slit-lamp examination. Fundus photography showed a distributed yellow-white lesion in her macular region (Fig. 2a). SD-OCT imaging revealed disruption of the EZ zone with minimal sub-retinal fluid and a slight elevation of RPE, while no choroidal hyper-or hypo-transmission below the level of RPE was observed (Fig. 2b). A follow-up without any treatment was advised. Two weeks later, the patient came back with a complaint of decreased visual acuity, which was 20/200 (6/60 in Snellen visual acuity of 6 meters) in the right eye. A small yellow-white lesion appeared in the inferior nasal of fovea (Fig. 2c). SD-OCT imaging showed a moderate reflective material under RPE with disruption of BM (Bruch’s membrane), and hyper-transmission in the choroid (Fig. 2d). The 3×3 mm SD-OCTA en face image showed an abnormal vascular network (Fig. 2e-2f). As the disease progressed, SD-OCT images began to show an area of choroidal hypo-transmission adjacent to the areas of a choroidal hyper-transmission (Fig. 2g). The patient was diagnosed with CNV secondary to PIC. We advised the patient to receive anti-VEGF treatment, but she refused, which made the deterioration of the disease (Fig. 2h). Finally, the patient agreed to receive anti-VEGF, and her BCVA improved to 20/125 (6/38 in Snellen visual acuity of 6 meters), accompanied with the shrinkage of the neovascularization (Fig. 3).