GENETIC FACTORS AND CHARACTERISTICS ON SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY ARE ASSOCIATED WITH CHOROIDAL THICKNESS IN ABCA4 -RELATED RETINOPATHY.

PURPOSE: To investigate the possible correlation factors of choroidal thickness in ABCA4 -related retinopathy. METHODS: A total of 66 patients were included in the cohort. It is a retrospective, cross-sectional laboratory investigation. The patients were tested using whole-exon sequencing and ophthalmic examinations, including slit-lamp examinations, best-corrected visual acuity, spectral-domain optical coherence tomography, fundus photograph, and fundus autofluorescence. RESULTS: Besides demographic characteristics (age, onset age, duration), we selected genetic factors and ocular characteristics on spectral-domain optical coherence tomography as the candidates related to choroidal thickness. Mutation type (inframe mutation or premature termination codon), epiretinal membrane, retinal pigment epithelium- Bruch membrane integrity, and macular curvature changes were identified as related factors to choroidal thickness in ABCA4 -related retinopathy after the adjustment of Logistic LASSO regression. CONCLUSION: Mutation type, epiretinal membrane, retinal pigment epithelium-Bruch membrane integrity, and macular curvature changes are related factors to choroidal thinning. These findings could provide us a further understanding for the pathological process and clinical features of ABCA4 mutation.

Double-dose investigation of aflibercept in neovascular age-related macular degeneration (DIANA): a real-world study.

BACKGROUND: To investigate the clinical effects of double-dose (4 mg) aflibercept treatment in neovascular age-related macular degeneration (nAMD), compared with the standard-dose (2 mg) treatment. METHODS: A total of 108 eyes from 97 patients with nAMD and received intravitreal aflibercept 2 mg and/or 4 mg treatment were retrospectively reviewed. The changes of central macular thickness (CMT)/ pigmental epithelium detachment height and the recurrence rate of exudation during the 12-month follow-up were compared between the 2 mg group and the 4 mg group. Self-control comparisons (2 mg switch to 4 mg) were also made between two regimens. RESULTS: Compared with the 2 mg group, tendencies of lower intraretinal fluid incidence and more CMT reduction were observed in the 4 mg group. The later one was also observed when eyes switching from 2 mg to 4 mg regimen. The median remission interval was 5 months in the 4 mg group, 2 months longer than the 3 months in the 2 mg group (P = 0.452). Injections needed in the 4 mg group were 3.644 ± 1.670, less than the 4.286 ± 2.334 injections in the 2 mg group within 12 months as well (P = 0.151). However, no associated vision benefits were gained from the double-douse regimen. No markedly increased-intraocular pressure events, or other adverse events were found in two groups. CONCLUSIONS: Compared to the aflibercept 2 mg treatment in nAMD, tendencies of anatomic gains and relieving treatment burden were brought by the aflibercept 4 mg treatment. This study may have additional importance, given the further application of high-dose aflibercept in real-world settings.

OUTER RETINAL TUBULATION IN BIETTI CRYSTALLINE DYSTROPHY ASSOCIATED WITH THE RETINAL PIGMENT EPITHELIUM ATROPHY.

PURPOSE: To determine the prognostic value of outer retinal tubulation (ORT) in the eyes of a Chinese cohort with Bietti crystalline dystrophy (BCD). METHODS: This retrospective, multicenter cohort study enrolled 42 patients with clinically and genetically diagnosed BCD. Eighty eyes with good-quality images of spectral domain optical coherence tomography were included. Demographic details and clinical data were collected. The characteristics of ORT, including prevalence, location, and morphologic characteristics were analyzed. RESULTS: Forty-two patients with BCD harbored potentially CYP4V2 disease-causing mutations. The mutation spectrum comprised 17 unique variants, 9 of which were novel. Fifty-two of these 80 eyes demonstrated evidence of ORT. The incidence of ORT is significantly higher in Stage 2 than other stages ( P < 0.001). ORT was mainly bilateral and located at the margin of the atrophic area of retinal pigment epithelium (RPE), and dynamically changed with the progressive RPE atrophy. The process of RPE atrophy was slower in eyes with ORT ( P = 0.017), with significantly longer intact RPE width in Stage 3 ( P = 0.024). Eyes with ORT had slower vision loss than eyes without ORT ( P = 0.044). CONCLUSION: ORT may be a sign of the onset of RPE atrophy in early-stage BCD and may suggest less risk of rapid progression in late-stage BCD.

Appearance of retinal arterial macroaneurysms in patients using swept-source optical coherence tomographic angiography.

BACKGROUND: Retinal arterial macroaneurysm (RAM) is a common clinical disease leading to vision loss in elderly individuals. The appropriate interpretation of swept-source optical coherence tomographic angiography (SS-OCTA), a noninvasive examination, is easy and convenient for detecting the status of RAMs and guiding treatment. METHODS: The objectives of this study were to describe the morphologic characteristics of RAMs using SS-OCTA and to observe whether there are differences in the morphologies of RAMs between SS-OCTA and fundus fluorescein angiography (FFA), before and after treatment. We retrospectively evaluated twenty-two eyes of 22 patients who were diagnosed with RAMs. All patients underwent a complete ophthalmologic examination, including a review of medical records, best-corrected visual acuity (BCVA), fundus photography, FFA and SS-OCTA. RAMs were recorded by SS-OCTA before any treatment or observation decisions were made. The morphologic findings of the RAMs on SS-OCTA were investigated. RESULTS: On SS-OCTA, RAMs can show local dilatation or an irregular linear blood flow signal, and the dilated cystic lumen may show thrombosis with a low reflection signal. After treatment, the shape of the RAMs will show reactive changes. The findings on SS-OCTA are not very consistent with those on FFA. CONCLUSIONS: The same RAM may have different manifestations on OCTA and FFA, and OCTA can more conveniently reflect the changes in blood flow signals and treatment response of RAMs.

Automatic Segmentation of Hyperreflective Foci in OCT Images Based on Lightweight DBR Network.

Hyperreflective foci (HF) reflects inflammatory responses for fundus diseases such as diabetic macular edema (DME), retina vein occlusion (RVO), and central serous chorioretinopathy (CSC). Shown as high contrast and reflectivity in optical coherence tomography (OCT) images, automatic segmentation of HF in OCT images is helpful for the prognosis of fundus diseases. Previous traditional methods were time-consuming and required high computing power. Hence, we proposed a lightweight network to segment HF (with a speed of 57 ms per OCT image, at least 150 ms faster than other methods). Our framework consists of two stages: an NLM filter and patch-based split to preprocess images and a lightweight DBR neural network to segment HF automatically. Experimental results from 3000 OCT images of 300 patients (100 DME,100 RVO, and 100 CSC) revealed that our method achieved HF segmentation successfully. The DBR network had the area under curves dice similarity coefficient (DSC) of 83.65%, 76.43%, and 82.20% in segmenting HF in DME, RVO, and CSC on the test cohort respectively. Our DBR network achieves at least 5% higher DSC than previous methods. HF in DME was more easily segmented compared with the other two types. In addition, our DBR network is universally applicable to clinical practice with the ability to segment HF in a wide range of fundus diseases.

Efficacy and safety of iodized lecithin tablets versus spironolactone in alleviating central serous retinopathy among Chinese patients with uncontrolled diabetes.

To compare the effectiveness and safety of spironolactone versus lecithin-bound iodine in patients with central serous retinopathy (CSR). Chinese diabetes patients aged>18 years with CSR with persistent increased level of subretinal fluid (SRF) were enrolled. Subjects were randomized to receive either oral lecithin-bound iodine (390µg/kg/day) or oral spironolactone (50mg/day) for 6 months. A total of 200 patients were randomized and completed the study. Compared to spironolactone group, patients treated with lecithin-bound iodine had greater proportion of eye with complete resolution (87% vs 81%, p>0.005). Higher improvement in height of SRF was observed in lecithin-bound iodine-treated patients as compared with Spironolactone-treated patients (91.2[87.5] vs 142.5 [121.1]; p>0.005). However, no statistically significant difference was observed on none of comparisons. Compared to Spironolactone, the patients treated with lecithin-bound iodine had greater improvement in lesion size, central macular thickness and best-corrected visual acuity. However, no statistically significant difference was observed in any of parameter assessed. (p>0.005). The results of the present study suggested that the lecithin-bound iodine was found more effective (nnumerically) than spironolactone in Chinese diabetes patients with CSR.

Comprehensive analysis of the PRPF31 gene in retinitis pigmentosa patients: Four novel Alu-mediated copy number variations at the PRPF31 locus.

Retinitis pigmentosa (RP) is a monogenic disease characterized by irreversible degeneration of the retina. PRPF31, the second most common causative gene of autosomal dominant RP, frequently harbors copy number variations (CNVs), but the underlying mechanism is unclear. In this study, we summarized the phenotypic and genotypic characteristics of 18 RP families (F01-F18) with variants in PRPF31. The prevalence of PRPF31 variants in our cohort of Chinese RP families was 1.7% (18/1024). Seventeen different variants in PRPF31 were detected, including eight novel variants. Notably, four novel CNVs encompassing PRPF31, with a proportion of 22.2% (4/18), were validated to harbor gross deletions involving Alu/Alu-mediated rearrangements (AAMRs) in the same orientation. Among a total of 12 CNVs of PRPF31 with breakpoints mapped on nucleotide-resolution, 10 variants (83.3%) were presumably mediated by Alu elements. Furthermore, we described the correlation between the genotypes and phenotypes in PRPF31-related RP. Our findings expand the mutational spectrum of the PRPF31 gene and provide strong evidence that Alu elements of PRPF31 probably contribute to the susceptibility to genomic rearrangement in this locus.

Efficacy of MP-3 microperimeter biofeedback fixation training for low vision rehabilitation in patients with maculopathy.

BACKGROUND: To evaluate the efficacy of MP-3 microperimeter biofeedback fixation training (MBFT) in vision rehabilitation of low-vision patients affected by macular disease with central vision loss. METHODS: Seventeen eyes (7 age-related macular degeneration, 10 myopic maculopathy) of 17 patients were included in this prospective, interventional study. The preferred retinal locus was determined by comprehensive ophthalmoscopic fundus evaluation including fundus photography, autofluorescence, optical coherence tomography, and microperimetry. The rehabilitation consisted of three 10-min sessions per eye to be performed twice per week for 20 consecutive weeks using the MP-3 microperimeter. Best corrected visual acuity (BCVA), reading speed, mean central sensitivity, the percentages of fixation points within specified regions, bivariate contour ellipse area (BCEA) and the 25-item National Eye Institute visual function questionnaire (NEI-VFQ-25) were recorded pre- and post-training. RESULTS: The final BCVA, reading speed and mean central sensitivity all showed significant improvements after rehabilitation (P <  0.0001, P = 0.0013, and P = 0.0002, respectively). The percentages of fixation points located within 2° and 4° diameter circles both significantly increased after training (P = 0.0008 and P = 0.0007, respectively). The BCEA encompassing 68.2, 95.4, 99.6% of fixation points were all significantly decreased after training (P = 0.0038, P = 0.0022, and P = 0.0021, respectively). The NEI-VFQ-25 scores were significantly increased at the end of the rehabilitation training (P <  0.0001). CONCLUSION: Rehabilitation with MP-3 MBFT is a user-friendly therapeutic option for improving visual function, fixation stability, and quality of life in advanced macular disease. TRIAL REGISTRATION: The prospective study was registered with the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ). TRIAL REGISTRATION NUMBER: ChiCTR2000029586 . Date of registration: 05/02/2020.

Long-term Visual Outcomes and Causes of Vision Loss in Chronic Central Serous Chorioretinopathy.

PURPOSE: To evaluate the long-term visual outcomes and causes of vision loss in chronic central serous chorioretinopathy (CSC). DESIGN: Retrospective, longitudinal study. PARTICIPANTS: A total of 133 participants (217 eyes) with chronic CSC. METHODS: A retrospective review of clinical and multimodal imaging data of patients with chronic CSC managed by 3 of the authors between May 1977 and March 2018. Multimodal imaging comprised color photography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence (FAF), and OCT. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) at the final visit; change in BCVA between first visit and 1-, 5-, and 10-year follow-up visits; and causes of vision loss at final visit. RESULTS: Data from 6228 individual clinic visits were analyzed. Mean age of patients at the first visit was 60.7 years, and mean period of follow-up from first to last visit was 11.3 years. The cohort included 101 male patients (75.9%). At the final visit, 106 patients (79.7%) maintained driving-standard vision with BCVA of 20/40 or better in at least 1 eye, and 17 patients (12.8%) were legally blind with BCVA of 20/200 or worse in both eyes. Mean BCVA at first visit was not significantly different from mean BCVA at 1- or 5-year follow-up visits (both P ≥ 0.65) but was significantly better than the mean BCVA at the 10-year follow-up visit (P = 0.04). Seventy-nine percent of eyes with 20/40 or better vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Ninety-two percent of eyes with 20/200 or worse vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Cystoid macular degeneration, choroidal neovascularization (CNV), outer retinal disruption on OCT, and FAF changes were associated with poorer vision at the final visit (all P ≤ 0.001). Multivariable analysis revealed that greater age at first visit was associated with greater BCVA change at the 10-year follow-up visit (P = 0.001). CONCLUSIONS: Chronic CSC can be a sight-threatening disease leading to legal blindness. Age at presentation and outer retinal changes on multimodal imaging were associated with long-term BCVA changes and may be predictors of long-term visual outcomes.

The Comparison of Morphologic Characteristics of Type 1 and Type 2 Choroidal Neovascularization in Eyes with Neovascular Age-Related Macular Degeneration using Optical Coherence Tomography Angiography.

PURPOSE: The purpose of this study was to use optical coherence tomography angiography (OCTA) to compare the morphology characteristics of type 1 and 2 choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD) patients. MATERIALS AND METHODS: This is a retrospective, observational study of 51 eyes with nAMD using OCTA from July 2016 through March 2017. RESULTS: In total, 51 eyes of 50 patients were included in the analysis. According to the anatomical classification based on OCT, 27 eyes (53%) were diagnosed with type 1 CNV, and 24 eyes (47%) were type 2 CNV. Type 2 CNV was characterized by smaller flow area, smaller greatest vascular caliber (GVC), smaller greatest linear dimension (GLD), and shorter duration of disease. The duration of disease only correlated with GVC (p = 0.026) in multivariate linear regression results. Meanwhile, GLD correlated with GVC and flow area whereas GVC was not associated with flow area. CONCLUSION: This study demonstrated that type 2 CNV was characterized by shorter duration of disease, smaller GVC, smaller GLD, and smaller flow area compared with type 1 CNV. Additionally, we showed that the duration of the disease correlated with GVC of the CNV.

Findings of OCT-angiography compared to fluorescein and indocyanine green angiography in central serous chorioretinopathy.

PURPOSE: The present study analyzed the appearances of optical coherence tomography angiography (OCTA) in patients with central serous chorioretinopathy (CSC) based on fluorescein angiography (FA) and indocyanine green angiography (ICGA). METHOD: In the current case series, 54 eyes of 50 patients diagnosed as CSC were evaluated retrospectively. OCTA, FA, and ICGA were performed on each patient. Two trained observers examined the OCTA images independently to confirm and compare the choriocapillary appearance with that on FA/ICGA. Also, the leakage of vessels on FA, perfusion of choroidal blood flow on ICGA, blood flow density, and vascular morphology on OCTA, as well as, the effect of serous retinal detachment (SRD) on imaging were observed. Furthermore, the image findings of contralateral eyes were included. RESULTS: 47/54 eyes (corresponding to 43 patients in 50 patients) were finally diagnosed with CSC that presented a leakage on FA and dilated vessels on ICGA, and the corresponding areas could be recognized on OCTA. However, in some of the cases (15 eyes, 31.9%), a portion of the leakage lesion on FA did not overlap completely with that on OCTA. On the OCTA B-scan, six eyes did not show a choriocapillary flow signal under subretinal fluid (SRF) with a median SRD height of 485 µm, despite the dilated vessels on ICGA. Approximately, 21 contralateral eyes without SRD and leakage presented dilated vessels on ICGA; however, only 13 eyes could be recognized on OCTA. In addition, seven eyes presented CSC on FA/ICGA but manifested explicit abnormal vascularization beneath the retinal pigment epithelium (RPE) on OCTA. CONCLUSION: FA/ICGA remains the gold standard for the diagnosis of CSC and cannot be completely replaced by OCTA. However, in some cases displaying hot-spots CNV, OCTA can contribute toward a definite diagnosis. The SRD height may exert a shielding effect on the choriocapillary flow signals on OCTA. Lasers Surg. Med. 50:987-993, 2018. © 2018 Wiley Periodicals, Inc.

Optical coherence tomography angiography of macular telangiectasia type 1: Comparison with mild diabetic macular edema.

OBJECTIVE: The present study aimed to investigate the characteristics of macular telangiectasia type 1 (Mac tel type 1) using spectral-domain optical coherence tomography angiography (OCTA) and compare them with the characteristics of mild diabetic macular edema (DME), to provide a new objective method for quick clinical diagnosis and treatment. METHODS: A retrospective comparative analysis of 9 Mac tel type 1, 15 DME, and 15 normal eyes was performed using fluorescein angiography, spectral-domain optical coherence tomography, and OCTA. The morphological changes, retinal vessel density, and nonperfused areas were evaluated using split-spectrum amplitude-decorrelation angiography algorithm. RESULTS: OCTA revealed obvious saccular capillary telangiectasia and loss of parafoveal vascular density of Mac tel type 1. However, a number of line segment hyperreflective signals around the macula and more distinct nonperfusion in DME were observed. The quantitative foveal avascular zone mean area in Mac tel type 1 was larger than that in the normal eyes (0.40 ± 0.06 mm2 vs. 0.88 ± 0.19 mm2 , P < 0.001). However, the area in DME (1.52 ± 0.38 mm2 ) was larger than that in Mac tel type 1 (P < 0.001), and the foveal zone area in DME (1.127 ± 0.05 mm2 ) was also lager than it in Mac tel (P < 0.05). The vascular density of the superficial layer reduced in both Mac tel type 1 and DME (compared with normal eyes). The difference between Mac tel type 1 (49.56 ± 5.23)% and DME(44.58 ± 3.82)% was significant in the superficial capillary layer (P < 0.01). The vascular density of the retinal deep layer also reduced in both Mac tel type 1 and DME (compared with normal eyes). The difference between Mac tel type 1 (53.78 ± 7.36)% and DME (53.64 ± 4.96)% was no significant in this layer (P > 0.05). CONCLUSION: Morphological differences between Mac tel 1 and DME can be observed on OCTA. Superficial vascular density and non-perfusion area may serve as a quantitative method to identify them. Lasers Surg. Med. 49:225-232, 2017. © 2017 Wiley Periodicals, Inc.

CENTRAL SEROUS CHORIORETINOPATHY TREATED WITH MINERALOCORTICOID ANTAGONISTS: A ONE-YEAR PILOT STUDY.

PURPOSE: To assess the treatment response to mineralocorticoid antagonists in a pilot study of patients diagnosed with central serous chorioretinopathy using multimodal imaging. METHODS: This retrospective observational case series included 23 eyes of 14 patients with central serous chorioretinopathy treated by a single physician (L.A.Y.) with either spironolactone, eplerenone, or both consecutively over a 12-month period. Choroidal thickness, central macular thickness, and best-corrected visual acuity were measured and compared with baseline values. Twelve eyes of 11 patients demonstrated subretinal fluid before or during the initiated treatment course. Subretinal fluid was measured and compared with baseline values in this subgroup. RESULTS: In all eyes (n = 23), best-corrected visual acuity improved at 12 months of treatment; however, central macular thickness and choroidal thickness showed no improvement. In the subgroup with subretinal fluid (n = 12), subretinal fluid was significantly decreased at 6 months and 12 months of treatment; however, central macular thickness, choroidal thickness, and best-corrected visual acuity showed no significant change. CONCLUSION: Mineralocorticoid antagonists may improve best-corrected visual acuity and decrease subretinal fluid in patients with central serous chorioretinopathy, but do not affect the choroidal or macular thickness. This pilot study demonstrates that mineralocorticoid receptor antagonists may be effective in treating central serous chorioretinopathy but warrants consideration for future research within a randomized clinical trial.

Detection of Choroidal Neovascularization in Central Serous Chorioretinopathy Using Optical Coherence Tomographic Angiography.

PURPOSE: To demonstrate the detection of choroidal neovascularization (CNV) in clinically diagnosed central serous chorioretinopathy (CSC) by optical coherence tomographic angiography (OCTA). METHODS: Seventy-five eyes of 70 patients were included. OCTA was performed on each patient. Two trained readers evaluated the images independently to confirm the diagnosis and identify CNV at the level of the outer retina. RESULTS: All studied eyes presented characteristics consistent with CSC based on eye examination and traditional imaging technologies, including fundus fluorescein angiography, which showed no evidence of CNV. However, OCTA revealed definite abnormal vascularization at the level of the outer retina in 8 eyes (10.7%) of 8 patients (11.4%). CONCLUSION: This study suggests that in some cases of CSC, OCTA could be an alternative option to detect CNV that is undetectable by other conventional imaging techniques.

Multimodal imaging findings in retinal deep capillary ischemia.

PURPOSES: To evaluate the multimodal imaging findings in retinal deep capillary ischemia (DCI). METHODS: This was a retrospective review of 5 eyes of 4 patients with sudden onset of paracentral scotomas caused by DCI. Multimodal imaging techniques, including color and red-free photographs, near-infrared reflectance, fluorescein angiography, and spectral-domain optical coherence tomography, were performed in all eyes, and the findings were correlated with microperimetry in two eyes. Imaging findings in DCI were compared with those of a cotton wool spot caused by superficial capillary ischemia (SCI). RESULTS: Unlike SCI, the imaging findings in DCI were subtler during both the acute and chronic phase, but specific optical coherence tomographic findings could readily differentiate these entities. Acute SCI showed inner retinal whitening, edema, and increased reflectivity, whereas acute DCI showed increased reflectivity of middle retinal layers. Chronic DCI showed retinal thinning with middle layer atrophy, whereas chronic SCI showed inner layer atrophy. In one patient, microperimetry showed a paracentral dense scotoma that corresponded well to the optical coherence tomographic findings. CONCLUSION: Deep capillary ischemia may represent a nonspecific finding of retinal ischemia and produces characteristic changes within the middle retinal layers, analogous to a deep cotton wool spot, but with distinct features differing from the superficial cotton wool spot which is seen in SCI. Among the various multimodal imaging techniques, optical coherence tomography seemed to be the most sensitive and specific technique in detecting DCI in both the acute and chronic phases.

Macular hole secondary to Valsalva retinopathy after doing push-up exercise.

BACKGROUND: Valsalva retinopathy and traumatic macular hole are common conditions, but macular hole secondary to Valsalva retinopathy is rarely reported. CASE PRESENTATION: A 34-year-old healthy man suffered Valsalva retinopathy after doing push-up exercise. During his follow-up visits, the best-corrected visual acuity (BCVA) measurements, fundus examinations and spectral-domain optical coherence tomography (SD-OCT) tests were performed. Three months later, the premacular hemorrhage was noticeably absorbed with an improvement of visual acuity. SD-OCT showed a lamellar macular hole with intact but thickened internal limiting membrane (ILM) with vitreal tractions on surface of the macular. Nine months after the first visit, his vision acuity was 20/25. The fundus examination showed a complete absorption of the macular hemorrhage. SD-OCT showed that the lamellar macular hole has enlarged, with thickened ILM on the surface. Seventeen months after the onset, the BCVA, fundus examination results and OCT findings were stable. CONCLUSIONS: Macular hole secondary to Valsalva retinopathy had been rarely reported and its mechanism needs further understanding. SD-OCT can be used to observe the evolvement of Valsalva retinopathy.