Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: To ascertain the characteristics of achromatopsia (ACHM) in Japan by analyzing the genetic and phenotypic features of patients with ACHM. METHODS: The medical records of 52 patients from 47 Japanese families who were clinically diagnosed with ACHM were reviewed in this retrospective observational study. RESULTS: Thirty-six causative variants of ACHM were identified in 26 families via whole-exome sequencing: PDE6C (12 families), CNGA3 (10 families), CNGB3 (two families), and GNAT2 (two families). However, none of the 6 causative variants that are known to cause ACHM, or the 275 other genes listed in RetNet, were observed in 19 families. A significant trend toward older age and worsening of ellipsoid zone disruption on optical coherence tomography images was observed (P < 0.01). Progressive ellipsoid zone disruptions were observed in 13 eyes of seven patients during the follow-up visits. These patients harbored one or more variants in PDE6C. CONCLUSION: The ACHM phenotype observed in this study was similar to those observed in previous reports; however, the causative gene variants differed from those in Europe. The low identification ratio of causative genes in whole-exome sequencing suggests the presence of unique hotspots in Japanese patients with ACHM that were not detectable via ordinal whole-exome sequencing.

DOI： 10.1097/IAE.0000000000004170

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP-allied diseases. METHODS: We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines. RESULTS: A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with EYS accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases. CONCLUSION: A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies.

DOI： 10.1136/jmg-2023-109750

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.7759/cureus.55716

PubMed

J-GLOBAL

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: This cross-sectional study aimed to clarify the differences in the retinal venous narrowing ratio (VNR) at retinal arteriovenous crossing by optical coherence tomography (OCT) among the eyes with branch retinal vein occlusion (BRVO), fellow eyes of patients with BRVO, and eyes of individuals without BRVO and to determine factors that influence the VNR. METHODS: We studied 31 eyes of young participants, 54 eyes of an older control group, 56 fellow eyes of patients with BRVO, and 48 eyes with BRVO. Cross-sectional OCT images were used to determine the VNR at two arteriovenous crossings per eye. RESULTS: Overall, 378 arteriovenous crossings were analyzed. The VNR of arterial overcrossings of fellow eyes (27.7% ± 11.1%) and BRVO eyes (27.3% ± 9.76%) were significantly higher than those in the young (16.0% ± 7.9%, all P < 0.001) and control (22.0% ± 8.81%, P < 0.001, P = 0.003, respectively) groups. The VNR of arterial overcrossings was significantly larger than that of venous overcrossings (24.0% ± 10.5% vs. 20.6% ± 13.0%, P = 0.021). A linear mixed-effects model showed that the VNR was significantly higher in arterial overcrossings, crossings with larger arterial internal diameters, smaller venous internal diameters, and participants with older age and a BRVO history. CONCLUSIONS: The VNR in arterial overcrossings was higher in BRVO eyes and even in the fellow eyes. Thus, a higher VNR in arterial overcrossings may contribute to BRVO development, and crossings with factors contributing to higher VNR might be associated with a risk of BRVO.

DOI： 10.1167/iovs.64.14.22

Open Access

PubMed

Language：Japanese   Publisher：(株)メディカル葵出版  

Language：English   Publishing type：Research paper (scientific journal)  

We aimed to investigate the increase in resistivity of the retinal artery in the branch retinal vein occlusion (BRVO)-affected area, and to visualize it. Thirty-two eyes of 32 patients with BRVO were measured by laser speckle flowgraphy (LSFG). The retinal artery and vein running to the BRVO-affected area and vertically symmetrical vessels in the unaffected area were examined. We applied the LSFG parameter beat strength over mean blur rate (BOM), calculated using a similar method to the pulsatility index used in Doppler flowmetry to evaluate resistivity of the vessels. Our results showed that the BOM map could clearly visualize the increase of resistivity in the retinal artery as a two-dimensional map. The BOM of the arteries in the affected area was significantly higher than that of the unaffected area (P = 0.001). Multiple regression analysis showed that the ratio of BOM in retinal arteries of the affected area to the unaffected was significantly associated with the extent of retinal hemorrhage (β = 0.447, P = 0.009). In conclusion, the index of resistivity of the retinal artery in the BRVO-affected area was higher and could be visualized in a two-dimensional map. These findings and techniques would contribute to elucidate the pathophysiology of BRVO.

DOI： 10.1038/s41598-021-99572-7

Open Access

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

We investigated morphological changes of retinal arteries to determine their association with the blood flow and systemic variables in type 2 diabetes patients. The patients included 47 non-diabetic retinopathy eyes, 36 mild or moderate nonproliferative diabetic retinopathy (M-NPDR) eyes, 22 severe NPDR (S-NPDR) eyes, 32 PDR eyes, and 24 normal eyes as controls. The mean wall to lumen ratio (WLR) measured by adaptive optics camera was significantly higher in the PDR groups than in all of the other groups (all P < 0.001). However, the external diameter of the retinal vessels was not significantly different among the groups. The mean blur rate (MBR)-vessel determined by laser speckle flowgraphy was significantly lower in the PDR group than in the other groups (P < 0.001). The WLR was correlated with MBR-vessel (r = - 0.337, P < 0.001), duration of disease (r = 0.191, P = 0.042), stage of DM (r = 0.643, P < 0.001), systolic blood pressure (r = 0.166, P < 0.037), and presence of systemic hypertension (r = 0.443, P < 0.001). Multiple regression analysis demonstrated that MBR-vessel (β = - 0.389, P < 0.001), presence of systemic hypertension (β = 0.334, P = 0.001), and LDL (β = 0.199, P = 0.045) were independent factors significantly associated with the WLR. The increased retinal vessel wall thickness led to a narrowing of lumen diameter and a decrease in the blood flow in the PDR group.

DOI： 10.1038/s41598-021-84067-2

Open Access

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The purpose of this cross-sectional retrospective study was to determine the relationship between the retinal displacements and the retinal thickness in eyes with epiretinal membrane (ERM) after vitrectomy with internal limiting membrane (ILM) peeling. To accomplish this, we measured the retinal thickness using optical coherence tomography (OCT) and the retinal displacement using OCT angiography to obtain 3 mm × 3 mm en face images before, and 2, 4, and 8 weeks following the surgery from 20 eyes of 20 patients. The distance between the retinal vessel bifurcations and the fovea was significantly displaced centrifugally and asymmetrically in the 4 quadrants postoperatively (P < 0.001). The foveal avascular zone (FAZ) was significantly enlarged, and the central foveal thickness (CFT) and the inner nuclear layer (INL) thickness were significantly thinner postoperatively. The displacements were significantly correlated with the changes in the FAZ area (r = 0.717, P < 0.001), the CFT (r = - 0.702, P < 0.001), and the INL thickness (r = - 0.702, P < 0.001). In conclusion, the distance between the retinal bifurcations and the fovea was asymmetrically expanded after the surgery and was significantly correlated with the morphological changes. These results indicate that a horizontal macular contraction is correlated with vertical retinal contraction in the eyes with an ERM.

DOI： 10.1038/s41598-020-70197-6

Open Access

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Purpose: To determine whether the blood flow in the superior retina is significantly different from that in the inferior retina, and to determine whether the posture affects the blood flow in the superior and inferior retina. Methods: The blood flow in the vessels around the optic nerve head was measured by laser speckle flowgraphy in the sitting position in 68 healthy subjects. The blood flow in the superior peripapillary retina was compared with that in the inferior peripapillary retina. The measurements of the blood flow were performed in the sitting position, and the effect of switching to a supine position was determined at 2, 4, 6, 8, 10, and 30 minutes after the switch. Results: The total relative flow volume (RFV)-all, RFV-artery, and RFV-vein were significantly greater in the superior retina than in the inferior retina (all P < 0.001). The mean diameter-all and mean diameter-artery in the superior retina were significantly larger than that in the inferior retina (all P < 0.05). The mean blur rate (MBR)-all, MBR-artery, and MBR-vein in the superior retina were also greater than that in the inferior retina (P < 0.001, P < 0.01, and P < 0.001, respectively). Although the ocular perfusion pressure was significantly changed with the postural alteration, the total RFV-all remained greater in the superior retina than in the inferior retina after the postural change. Conclusions: Clinicians need to be aware of the differences in the blood flow between the superior and inferior retinal peripapillary area when considering the mechanisms of retinochoroidal diseases.

DOI： 10.1167/iovs.61.5.27

Open Access

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Intraretinal cystoid cavities have been detected at the edges of macular holes (MHs) but their clinical characteristics and their relationship to the MH variables have not been determined. We measured the areas of the intraretinal cystoid cavity in 111 eyes with MHs in the OCT images preoperatively. Our results showed that the intraretinal cystoid cavities were located in the Henle fiber layer-outer nuclear layer (HFL-ONL) complex in 106 eyes and in the inner nuclear layer (INL) in 89 eyes. All were resolved after the initial vitrectomy to close the MH. The mean area of the cystoid cavity was greater in the HFL-ONL complex (55.9 ± 42.7 × 103 μm2) than in the INL (9.1 ± 9.8 × 103 μm2; P < 0.001). The area of the cystoid cavities was significantly correlated with the basal MH size (r = 0.465,P < 0.001), the external limiting membrane height (r = 0.793, P < 0.001), and the maximum retinal thickness (r = 0.757, P < 0.001). The area of the cystoid cavities was significantly correlated with the preoperative best-corrected visual acuity (BCVA; r = 0.361, P < 0.001), but not with the postoperative BCVA or the integrity of any of the outer retinal microstructural bands. The presence of intraretinal cystoid cavities was related to some morphological characteristics, but not to the postoperative BCVA or the restoration of the outer retinal bands.

DOI： 10.1038/s41598-020-59295-7

Open Access

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

It has been reported that the macular region of the retina is displaced after vitrectomy with internal limiting membrane (ILM) peeling in eyes with macular hole (MH), but the displacements of the deeper layers of the eye, e.g. RPE and choroid are unclear following the surgery. We used optical coherence tomography (OCT) and OCT angiography (OCTA) to obtain 3 mm × 3 mm en face images before, and 2, 4, and 8 weeks following the vitrectomy with internal limiting membrane (ILM) peeling from 22 eyes of 22 patients with a MH. The OCT and OCTA images showed displacements of the fovea and choroidal intermediate vessels postoperatively. The degree of displacement of the choroid was significantly less than that of the retina (P < 0.001). The displacements of the choroidal bifurcations were significantly correlated to their preoperative distance from the optic disc (r = -0.467, P < 0.001) and they were significantly correlated with the retinal displacements (r = 0.535, P < 0.001). The retina was displaced inferiorly and centripetally, but these localized displacements were not observed in the choroid. In conclusion, clinicians need to be aware of these displacements when evaluating the subfoveal choroid following the surgery because the displacement is different between the retina and the choroid.

DOI： 10.1038/s41598-019-54106-0

Open Access

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

We evaluated whether the reduction of macular vessel density was correlated with the number of intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents in eyes with a branch retinal vein occlusion (BRVO). The mean vessel density was determined by optical coherence tomography angiography in 29 eyes with macular edema associated with a BRVO. Our results showed that the mean vessel density in the group that had a resolution of the macular edema after one anti-VEGF injection was significantly higher than group that had a recurrence of the macular edema (P = 0.028). Single regression analysis showed that the number of intravitreal injections was significantly correlated with the reduction of the modified vessel density (r = -0.421, P = 0.023) and systemic hypertension (r = 0.377, P = 0.044). Multiple stepwise regression analysis showed that the reduction of the modified vessel density (β = -0.442, P = 0.009) and hypertension (β = 0.403, P = 0.016) were independent factors associated with the number of intravitreal injections. We conclude that the vessel density reduction can be used to predict whether recurrences of the macular edema will develop after the initial anti-VEGF injection in eyes with macular edema associated with a BRVO.

DOI： 10.1038/s41598-019-52732-2

Open Access

PubMed

Publishing type：Research paper (scientific journal)  

Scopus

Language：Japanese   Publisher：眼科臨床紀要会  

Language：Japanese   Publisher：眼科臨床紀要会  

Language：Japanese   Publisher：眼科臨床紀要会  

Language：Japanese   Publisher：(公財)日本眼科学会  

Language：Japanese   Publisher：眼科臨床紀要会  

Language：Japanese   Publisher：(公財)日本眼科学会  

Language：Japanese   Publisher：眼科臨床紀要会  

Language：Japanese   Publisher：(公社)日本超音波医学会