EYSは日本における網膜色素変性の主たる原因遺伝子である：多段階的な遺伝子スクリーニングにより明らかとなった日本人網膜色素変性患者の遺伝的背景

京都大学新制・課程博士博士(医学)甲第23098号医博第4725号新制||医||1050(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 小杉 眞司, 教授 滝田 順子, 教授 小川 誠司学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Changes in the deep vasculature assessed using anterior segment OCT angiography following trabecular meshwork targeted minimally invasive glaucoma surgery

The effect of trabecular meshwork (TM)-targeted minimally invasive glaucoma surgery (MIGS) on the vasculature assessed using anterior segment (AS)-optical coherence tomography angiography (OCTA) has not been established. In this prospective, longitudinal study, we investigated changes in the deep vasculature following TM-targeted MIGS using AS-OCTA for open-angle glaucoma in 31 patients. AS-OCTA images of the sclera and conjunctiva at the nasal corneal limbus were acquired preoperatively and 3 months postoperatively, and the vessel densities (VDs) of the superficial (conjunctival) and deep (intrascleral) layers were calculated. The VDs before and after MIGS were compared, and the factors associated with the change in VD following MIGS were analyzed. The mean deep VD decreased from 11.98 ± 6.80% at baseline to 10.42 ± 5.02% postoperatively (P = 0.044), but superficial VD did not change (P = 0.73). The multivariate stepwise regression analysis revealed that deep VD reduction was directly associated with IOP reduction (P < 0.001) and preoperative IOP (P = 0.007) and inversely associated with preoperative deep VD (P < 0.001). The deep VD reduction following MIGS was significant in the successful group (21 eyes) (P = 0.032) but not in the unsuccessful group (10 eyes) (P = 0.49). The deep VDs assessed using AS-OCTA decreased following TM-targeted MIGS, especially in the eyes with good surgical outcomes

Detection Sensitivity of Retinitis Pigmentosa Progression Using Static Perimetry and Optical Coherence Tomography

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

MACULAR BLOOD FLOW CHANGES IN BRANCH RETINAL VEIN OCCLUSION EXAMINED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY VARIABLE INTERSCAN TIME ANALYSIS

Purpose: To examine the relationship between changes in retinal blood flow and the recurrence of macular edema in eyes with branch retinal vein occlusion. Methods: This observational study included 32 eyes in 32 patients (18 men and 14 women) with branch retinal vein occlusion who visited the Department of Ophthalmology at Kyoto University Hospital (February 2021–November 2021). At the time of inclusion in the study, each patient underwent optical coherence tomography angiography on a macular area measuring 4 × 4 mm2. For variable interscan time analysis, different interscan times were set at 7.6 (IST7.6) and 20.6 ms (IST20.6) for the optical coherence tomography angiography. The parafoveal vessel densities were measured sectorally at IST7.6 and IST20.6, and their relationship with the longitudinal changes evident in the retinal thicknesses during the variable interscan time analysis examination and 2 months later was evaluated. Results: The parafoveal vessel densities in the affected sector was significantly greater at IST20.6 than at IST7.6 (P = 0.011). At 2 months after the variable interscan time analysis examination, 6 patients (19%) showed recurrence of macular edema involving the fovea. The difference in the parafoveal vessel densities (IST20.6 − IST7.6) in the affected sector was significantly associated with longitudinal retinal thickening in the corresponding parafovea (P = 0.020) and fovea (P = 0.014). Conclusion: In eyes with branch retinal vein occlusion, optical coherence tomography angiography variable interscan time analysis facilitated the detection of retinal blood flow changes that might be predictive for the recurrence of macular edema

Prediction of trabecular meshwork-targeted micro-invasive glaucoma surgery outcomes using anterior segment OCT angiography

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.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 < 0.001). These results indicate that intrascleral vasculature assessed using preoperative AS-OCTA was negatively correlated with surgical success and IOP reduction resulting from trabecular meshwork-targeted MIGS. AS-OCTA images might help predict MIGS outcomes

Macular retinal circulation in healthy eyes examined by optical coherence tomography angiography extended interscan time analysis.

PurposeTo examine whether extended interscan time (IST) on optical coherence tomography angiography (OCTA) can detect slow retinal blood flow, which is undetectable on default IST, in the healthy macula.MethodsOCTA (OCT-A1, Canon Inc.) scanning of a macular area measuring 4 × 4 mm2 of 14 healthy eyes of 14 healthy volunteers with no history or evidence of systemic and macular diseases was performed. ISTs were set at 7.6 (IST7.6, default setting), 12.0 (IST12.0), and 20.6 msec (IST20.6). Ten OCTA images were acquired at each IST, and an averaged image was created. For each averaged OCTA image obtained at IST7.6, IST12.0, and IST20.6, we defined the area surrounded by the innermost capillary ring as the foveal avascular zone (FAZ). We qualitatively evaluated the delineation of the capillaries consisting of the FAZ and quantitatively measured the FAZ area at each IST.ResultsExtensions from IST7.6 to IST12.0 and IST20.6 could newly delineated retinal capillaries that were undetectable at the default IST; new capillaries were detected in 10 (71%) eyes at IST12.0 and 11 (78%) eyes at IST20.0. The FAZ areas were 0.334 ± 0.137 mm2, 0.320 ± 0.132 mm2, and 0.319 ± 0.129 mm2 for IST7.6, IST12.0, and IST20.0, respectively; the FAZ areas at IST12.0 and IST20.0 were significantly decreased compared with that at IST7.6 (p = 0.004 and 0.002, respectively).ConclusionIn OCTA for healthy participants, extensions of the ISTs newly detected retinal capillaries with slow blood flow around FAZ. The FAZ shapes varied with different ISTs. Thus, the blood flow dynamics are not physiologically uniform around FAZ. Compared with conventional OCTA, this protocol enables a more detailed evaluation of retinal circulation and provides a better understanding of the physiological circulatory status of the healthy retina, and may enable the assessment of circulation in the very early stages in diseased eyes

Five-year visual outcomes after anti-VEGF therapy with or without photodynamic therapy for polypoidal choroidal vasculopathy

[Background/aims] To 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). [Methods] This 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. [Results] In 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). [Conclusions] A 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

Comparison of the FAZ areas obtained at IST_7.6 and IST_12.0.

In the graph on the left, the vertical axis represents the FAZ area corrected by the axial length obtained at IST7.6 and IST12.0, whereas the horizontal axis represents IST. In the graph on the right, the vertical axis represents the area of FAZ obtained at IST7.6 and IST12.0 divided by the area of FAZ obtained at IST7.6; the horizontal axis represents IST. The FAZ areas decreased significantly at IST12.0 compared with that at IST7.6.</p