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ImportanceThere is no widespread effective treatment to halt the progression of retinitis pigmentosa. Consequently, adequate assessment and estimation of residual visual function are important clinically.ObjectiveTo examine whether deep learning can accurately estimate the visual function of patients with retinitis pigmentosa by using ultra-widefield fundus images obtained on concurrent visits.Design, Setting, and ParticipantsData for this multicenter, retrospective, cross-sectional study were collected between January 1, 2012, and December 31, 2018. This study included 695 consecutive patients with retinitis pigmentosa who were examined at 5 institutions. Each of the 3 types of input images—ultra-widefield pseudocolor images, ultra-widefield fundus autofluorescence images, and both ultra-widefield pseudocolor and fundus autofluorescence images—was paired with 1 of the 31 types of ensemble models constructed from 5 deep learning models (Visual Geometry Group–16, Residual Network–50, InceptionV3, DenseNet121, and EfficientNetB0). We used 848, 212, and 214 images for the training, validation, and testing data, respectively. All data from 1 institution were used for the independent testing data. Data analysis was performed from June 7, 2021, to December 5, 2022.Main Outcomes and MeasuresThe mean deviation on the Humphrey field analyzer, central retinal sensitivity, and best-corrected visual acuity were estimated. The image type–ensemble model combination that yielded the smallest mean absolute error was defined as the model with the best estimation accuracy. After removal of the bias of including both eyes with the generalized linear mixed model, correlations between the actual values of the testing data and the estimated values by the best accuracy model were examined by calculating standardized regression coefficients and P values.ResultsThe study included 1274 eyes of 695 patients. A total of 385 patients were female (55.4%), and the mean (SD) age was 53.9 (17.2) years. Among the 3 types of images, the model using ultra-widefield fundus autofluorescence images alone provided the best estimation accuracy for mean deviation, central sensitivity, and visual acuity. Standardized regression coefficients were 0.684 (95% CI, 0.567-0.802) for the mean deviation estimation, 0.697 (95% CI, 0.590-0.804) for the central sensitivity estimation, and 0.309 (95% CI, 0.187-0.430) for the visual acuity estimation (all P Conclusions and RelevanceResults of this study suggest that the visual function estimation in patients with retinitis pigmentosa from ultra-widefield fundus autofluorescence images using deep learning might help assess disease progression objectively. Findings also suggest that deep learning models might monitor the progression of retinitis pigmentosa efficiently during follow-up.

Inherited retinal dystrophy (IRD) patients often experience photophobia. However, its mechanism has not been elucidated. This study aimed to investigate the main wavelength of light causing photophobia in IRD and difference among patients with different phenotypes. Forty-seven retinitis pigmentosa (RP) and 22 cone-rod dystrophy (CRD) patients were prospectively recruited. We designed two tinted glasses: short wavelength filtering (SWF) glasses and middle wavelength filtering (MWF) glasses. We classified photophobia into three types: (A) white out, (B) bright glare, and (C) ocular pain. Patients were asked to assign scores between one (not at all) and five (totally applicable) for each symptom with and without glasses. In patients with RP, photophobia was better relieved with SWF glasses {“white out” (p

Optical coherence tomography angiography (OCTA) is a new technique for non-invasive imaging of blood vessels, allowing combined evaluation of both deep and surface vessels. The purpose of this study was to evaluate the post-trabeculectomy longitudinal changes in complete avascular area (CAA) of filtering blebs using anterior segment (AS-) OCTA and their association with surgical outcomes. This study included 57 eyes of 53 patients who had undergone trabeculectomy with mitomycin C. AS-OCTA images of filtering bleb were acquired at 3 and 6 months after trabeculectomy, and at 1 month in possible cases. CAAs, regions where complete blood flow was not depicted in AS-OCTA images, were evaluated for their presence, extent, and change over time. CAAs were detected in 37 eyes (65%) and 33 eyes (58%) at 3 and 6 months postoperatively, respectively. The extent of CAAs reduced over time after surgery in most cases. No parameters related to CAAs were significantly associated with surgical success (i.e., intraocular pressure (IOP) ≤ 12 mmHg and IOP reduction > 20% without medication). In conclusion, although it is difficult to predict surgical success by CAA itself, AS-OCTA may be useful for the objective evaluation of the vascularity of filtering blebs.

We performed a prospective, longitudinal study to investigate the association between the preoperative intrascleral vasculature assessed using anterior segment (AS)-optical coherence tomography angiography (OCTA) and surgical outcomes of trabecular meshwork-targeted micro- or minimally invasive glaucoma surgery (MIGS). We included 37 patients with primary open-angle glaucoma. Preoperative AS-OCTA images of the sclero-conjunctiva of the nasal corneal limbus were acquired in the superficial (conjunctival) and deep (intrascleral) layers. The vessel densities (VDs) of each layer were measured separately in the entire area, limbal side, and fornix area. Surgical success was determined by postoperative intraocular pressure (IOP) and IOP reduction. Twenty-three and 14 eyes were classified as having successful and unsuccessful outcomes, respectively. The deep VDs of the entire area and fornix area were significantly lower in the successful group (P = 0.031 and P = 0.009). The success rate was significantly higher for eyes with a lower deep VD than for eyes with a higher deep VD. A greater IOP reduction was significantly associated with lower deep VD in the fornix area (P = 0.022) and higher preoperative IOP (P, 前眼部OCTAを用いた線維柱帯切開術効果予測 --房水主流出路の可視化による緑内障手術予後予測の可能性--. 京都大学プレスリリース. 2021-09-09.

Concentric retinitis pigmentosa (RP), in which retinal degeneration is limited in the periphery, is rare and little information exists to date on the subject. Herein, we describe the clinical and genetic characteristics of this atypical form of RP. We retrospectively reviewed our database and identified 14 patients with concentric RP. Additionally, 14 patients with age-matched typical RP were also included. Patients with concentric RP had better visual acuity (logarithm of minimum angle of resolution −0.04 vs. 0.32, p = 0.047) and preserved ellipsoid zones (7630 µm vs. 2646 µm, p &lt, 0.001) compared to typical RP. The electroretinogram showed subnormal but recordable responses in patients with concentric RP. Genetic testing was done in nine patients with concentric RP and revealed causative mutations in the EYS gene in one patient and the RP9 gene in one patient. Two patients had myotonic dystrophy and the diagnosis was revised as myotonic dystrophy-associated retinopathy. Concentric RP is a rare, atypical form of RP with better visual function. There is some overlap in the causative genes in concentric and typical RP. Myotonic dystrophy-associated retinopathy is an important differential diagnosis.

Next-generation sequencing (NGS) has greatly advanced the studies of causative genes and variants of inherited diseases. While it is sometimes challenging to determine the pathogenicity of identified variants in NGS, the American College of Medical Genetics and Genomics established the guidelines to help the interpretation. However, as to the genetic screenings for patients with retinitis pigmentosa (RP) in Japan, none of the previous studies utilized the guidelines. Considering that EYS is the major causative gene of RP in Japan, we conducted stepwise genetic screening of 220 Japanese patients with RP utilizing the guidelines. Step 1–4 comprised the following, in order: Sanger sequencing for two major EYS founder mutations; targeted sequencing of all coding regions of EYS; whole genome sequencing; Sanger sequencing for Alu element insertion in RP1, a recently determined founder mutation for RP. Among the detected variants, 2, 19, 173, and 1 variant(s) were considered pathogenic and 8, 41, 44, and 5 patients were genetically solved in step 1, 2, 3, and 4, respectively. Totally, 44.5% (98/220) of the patients were genetically solved, and 50 (51.0%) were EYS-associated and 5 (5.1%) were Alu element-associated. Among the unsolved 122 patients, 22 had at least one possible pathogenic variant.

OBJECTIVES: We investigated in vivo light-induced photoreceptor damage in retinitis pigmentosa (RP) using spectral-domain optical coherence tomography (SD-OCT) images. METHODS: We retrospectively reviewed patients with genetic diagnosis of EYS-associated RP. The outer nuclear layer (ONL) thickness under retinal vessels was measured on SD-OCT vertical scans. As a control, we measured adjacent ONL thickness 100 μm superior and inferior from the vessel. Same measurements were performed in healthy subjects. We calculated the ratio of ONL thickness under vessel divided by the average of adjacent ONL thickness and defined as ONL preservation ratio. In patients with RP, the length of ellipsoid zone (EZ) from the fovea was also measured with SD-OCT vertical scans. RESULTS: Thirty EYS-associated RP patients and 25 healthy subjects were included. In both groups, ONL thickness overshadowed by retinal vessels was not significantly different from that of adjacent area. However, ONL preservation ratio of RP was larger than that of healthy control in both superior and inferior retina (1.03 vs 0.97; p

PURPOSE The purpose of this study was to investigate the lamina cribrosa (LC) microvasculature using swept-source optical coherence tomography angiography (OCTA) images that have been processed using multiple image averaging and a projection-resolved algorithm. OCTA has recently gained popularity for assessing retinal and choroidal microvasculature. However, it is not known if the LC microvasculature, which likely holds important information for further understanding of glaucoma, can be visualized with OCTA. METHODS One normal subject and 1 glaucomatous subject were enrolled and optic disc 3×3 mm swept-source OCTA cubic images were obtained for each subject. Anterior LC slab frames were developed, and the averaged images were created using 3 frames. Images were examined both with and without removal of projection artifacts. RESULTS The OCTA images of anterior LC slabs before projection artifact removal contained information on superficial and deep layer vessel blood flow. However, after projection artifact removal, fewer blood flow signals remained. These en face OCTA images showed flow signals on or immediately adjacent to lamina beams, but not inside lamina pores. The glaucomatous eye had a sectoral reduction in LC microvasculature blood flow that was not detected in normal eye. CONCLUSIONS This is the first demonstration of imaging of the inner LC microvasculature, which, in agreement with previous histologic reports, was arranged in a polygonal pattern. Furthermore, glaucomatous eye had decreased flow signals in comparison with normal eye. Therefore, future imaging studies with OCTA may be helpful for identifying and better understanding LC pathologic changes associated with glaucoma.

Purpose To evaluate the diagnostic usefulness of multimodal imaging in patients with Bietti crystalline dystrophy (BCD). Design Retrospective cross-sectional study. Participants Patients with chorioretinal dystrophy accompanied by crystalline-like deposits. The right eyes of the patients were analyzed. Methods Fundus photograph, near-infrared reflectance (NIR), fundus autofluorescence (FAF), and OCT images were evaluated. Presence of hyperreflectivity on NIR, well-demarcated areas of decreased FAF, hyperreflective material at or on the retinal pigment epithelium–Bruch’s membrane complex, and outer retinal tubulation were graded for each patient. All exons and franking introns of CYP4V2 were screened using Sanger sequencing. Main Outcome Measures Sensitivity and specificity of the findings to discriminate patients with and without CYP4V2 mutation. Results In total, 33 patients were included in the study. Sanger sequencing revealed homozygous or compound heterozygous CYP4V2 mutations in 20 patients and heterozygous mutations in 2 patients. Among the investigated factors, hyperreflective appearance on NIR imaging yielded 100% sensitivity and 100% specificity in this cohort. The presence of outer retinal tubulation also was sensitive (95%), but specificity was moderate (45%). The revised diagnoses of patients without CYP4V2 mutations included retinitis pigmentosa, late-onset macular dystrophy, and central areolar choroidal dystrophy. Conclusions Multimodal imaging, especially NIR imaging, is useful to differentiate BCD patients with CYP4V2 mutations from patients with other chorioretinal dystrophies accompanied by crystalline-like retinal deposits.

Myopia is increasing rapidly worldwide. We performed a cross-sectional study to investigate the prevalence of posterior staphyloma, a complication of myopia, and its shape characteristics in relation to age, sex, and axial length (AL) in a Japanese community-based cohort. The right eyes of 3748 participants who underwent fundus photography and optical coherence tomography (OCT) examination were evaluated. Posterior staphyloma prevalence was evaluated using fundus photographs and OCT images. Furthermore, fundus shapes were analyzed by measuring local fundus curvatures on 6 mm cross-line OCT images at intervals of 1 µm. The mean and variance of the curvatures were calculated to represent the fundus shape of each eye for investigation of the relationship between fundus curvature and age, sex, and AL. Seventy-seven eyes (2.05%) had posterior staphyloma. The mean and variance of the fundus curvatures were significantly greater in women than in men and became greater with age, suggesting that the shape of the staphyloma was steeper and less smooth in women and elderly subjects. AL and mean curvature showed a significant correlation (P = 2 × 10−16, R = 0.480), which was significantly affected by age (P −16). Quantitative analysis of fundus shapes was useful for statistical analysis of posterior staphyloma in relation to age, sex, and AL.

Purpose: To compare the detection sensitivities of the progression of retinitis pigmentosa (RP) by automated perimetry to obtain the mean deviation (MD) and total point score and by optical coherence tomography (OCT) to determine the residual ellipsoid zone (EZ) length and thickness of retinal layers. Methods: Twenty-two eyes of 22 patients with RP who underwent annual automated perimetry (Humphrey Field Analyzer 10-2) and OCT examinations during the same period more than four times were included. Disease progression was evaluated using linear regression analysis with the least-squares method. The disease progression speed and interinspection fluctuations for the different examinations were compared using standardized values. The progression detection ability factor, defined as the average of the least squares divided by the square of annual change, was used to compare the sensitivities of the examinations for detecting the progression of RP. Results: EZ length showed a high correlation with MD (R = 0.87; P = 1.12E-07) at baseline. Disease progression was detected more frequently using EZ length (12/22 eyes) than using MD (3/22 eyes; P = 0.004) or central retinal thickness (1/11 eyes; P = 0.012). Linear regression using standardized values showed that the EZ length had the fastest annual change, with the smallest least absolute values. EZ length was more sensitive for detecting RP progression than MD, total point score, visual acuity, or central retinal thickness. Conclusions: EZ measurement was sensitive for detecting RP progression, and the results of this study indicate that EZ length is appropriate for end points in clinical trials. Translational Relevance: The study provides a basis for conducting future clinical trials.

BackgroundInherited retinal degeneration (IRD) refers to a heterogenous group of progressive diseases that cause death of photoreceptor cells and subsequent vision loss. These diseases often affect the peripheral retina, objective evaluation of which has been difficult until recently. Fundus autofluorescence (FAF) is a non-invasive retinal imaging technique that depicts the distribution of intrinsic fluorophores in the retina. The primary source of retinal autofluorescence is lipofuscin, which is contained in the retinal pigment epithelium (RPE). Excessive accumulation of lipofuscin and a window defect attributable to loss of photoreceptor pigment result in increased FAF whereas loss of the RPE results in decreased FAF. These changes can be seen during the course of IRD.MainbodyWhile conventional modalities are limited in their angle of view, recent technologic advances, known as wide-field and ultra-widefield FAF imaging, have enabled visualization of the far peripheral retina. Although clinical application of this technique in patients with IRD is still in its infancy, some studies have already indicated its usefulness. For example, an area with decreased FAF correlates well with a visual field defect in an eye with retinitis pigmentosa (RP) or cone-rod dystrophy. An abnormal FAF pattern may help in the diagnosis of IRD and associated diseases. In addition, female carriers of X-linked RP and female choroideremia show characteristic appearance. Conversely, absence of abnormal FAF despite severe retinal degeneration helps differentiation of cancer-associated retinopathy.ConclusionThis paper reviews the principles of FAF, wide-field imaging, and findings in specific diseases. Wide-field imaging, particularly wide-field FAF, will provide further information for the characteristics, prognosis, and pathogenesis of IRD.

Purpose Examine associations between the vasculature at arteriovenous (AV) crossings and the onset of branch retinal vein occlusion (BRVO). Methods We included 78 patients with major BRVO, 35 patients with macular BRVO, and 110 controls without BRVO and determined the vessel positions at AV crossings, where the first- or second-order branches of the retinal veins associate, using a viewing angle of 12 × 12 mm2 in optical coherence tomography angiography (OCTA). Results We reviewed 1349 and 1276 AV crossings in BRVO patients and control subjects, respectively. The proportions of venous overcrossing were 26.5%, 28.6%, and 26.8% at non-causative crossings in BRVO eyes, non-BRVO fellow eyes, and unaffected control eyes, respectively; however, the rate of venous overcrossings at the causative crossings was 45.1%. In OCTA analyses, we divided the branches into macular- or non-macular veins. The rate of venous overcrossing was 52.5% at causative crossings in major BRVO but was 28.6% in macular BRVO. Odds ratios for whether venous overcrossing was a risk factor for BRVO were 3.09 (95% confidence interval [CI], 1.96–4.88) and 0.94 (95% CI, 0.44–2.00) for non-macular veins and macular veins, respectively. The patients with major BRVO caused by venous overcrossing were younger than patients for whom the cause was arterial overcrossing (P < 0.001). The onset of macular BRVO did not differ between crossing patterns at causative crossings (P = 0.60). Conclusions In eyes with BRVO, venous overcrossing was a common angiographic feature at causative crossings and might be a risk factor for major BRVO onset.

Background/aimsTo evaluate the 5-year visual and anatomical outcomes after anti-vascular endothelial growth factor (VEGF) therapy alone or in combination with photodynamic therapy (PDT), followed by pro re nata (PRN) anti-VEGF therapy with or without PDT, for polypoidal choroidal vasculopathy (PCV).MethodsThis retrospective, observational study included 61 consecutive patients with treatment-naïve symptomatic PCV who were followed for 5 years. Twenty eyes (20 patients) initially received PDT and intravitreal injection of ranibizumab (IVR), followed by a PRN regimen of anti-VEGF therapy with or without PDT (combination group), while 41 eyes (41 patients) initially received only IVR every 3 months, followed by a PRN regimen of anti-VEGF monotherapy (IVR group). Macular atrophy including the fovea was confirmed using colour fundus photography and spectral-domain optical coherence tomography.ResultsIn both groups, the visual acuity (VA) at 1 year was better than the baseline VA, whereas the 3-year, 4-year and 5-year VA values were similar to the baseline VA. There was no significant difference in the 5-year VA, 5-year central retinal thickness and incidence of macular atrophy between the two groups (p=0.63, 0.72 and 0.06, respectively). In the combination group, the 5-year VA was correlated with the 5-year incidence of macular atrophy (p=0.02, r=0.51).ConclusionsA PRN regimen for PCV may have a limited effect for the long-term maintenance of improved VA. Macular atrophy may occur more frequently with combination therapy and is possibly associated with the 5-year VA. Thus, combination therapy should be carefully selected for patients susceptible to macular atrophy.

Purpose We investigate whether choriocapillaris deficits can be visualized in patients with retinitis pigmentosa (RP) using wide-angle swept-source optical coherence tomography angiography (OCTA), and whether angiography or structure en face images depict a wider area of residual choriocapillaris. Methods This cross-sectional study included 43 eyes of 43 consecutive patients with RP with a visual acuity ≥0.1, and 12 healthy eyes of 12 volunteers. Using an OCTA device (PLEX Eite 9000), we obtained angiography and structure en face images in the choriocapillaris. The residual choriocapillaris area in a 12 × 12 mm macular cube was measured manually. Results In patients with RP, the residual choriocapillaris area was 113.1 ± 41.9 and 64.0 ± 47.8 mm2 in angiography and structure images, respectively (P < 0.001). Concentric and vermicular choriocapillaris flow deficits were observed in 10 (23%) and 17 (40%) eyes of RP patients, respectively; no deficits were observed in 16 eyes (37%). Mean age was higher in eyes with concentric, vermicular, and nondeficit choriocapillaris. No healthy eye showed choriocapillaris deficits. Conclusions Using wide-angle swept-source OCTA, concentric and vermicular choriocapillaris flow deficits were observed in the eyes of RP patients. A comparison of angiography and structure en face images of the choriocapillaris in RP cases suggests that angiography images can evaluate a wider area of the choriocapillaris than structure images.