A case of recurrent follicular cholangitis leading to decompensated cirrhosis after left-sided hepatectomy.

Follicular cholangitis (FC) is a rare non-neoplastic biliary tract disease first reported in 2003. A 74-year-old woman underwent extended left hepatectomy with a diagnosis of intrahepatic cholangiocarcinoma. Histopathological examination of the surgical specimen demonstrated no malignant findings, and lymphocytic infiltration with lymphoid follicles was observed within the bile duct wall. Along with immunohistochemical findings, the patient was diagnosed with FC. More than 3 years after surgery, the patient exhibited elevated hepatobiliary enzymes and total bilirubin. Endoscopic retrograde cholangiography revealed stricture and dilation from the extrahepatic bile duct to the right intrahepatic bile duct. Histopathological findings uncovered lymphocytic infiltration without malignant results. It was concluded that bile duct stricture due to FC had newly developed in her remnant liver. Subsequently, the patient developed hypoalbuminemia, and abdominal computed tomography revealed atrophy of the remnant liver and ascites accumulation. Esophagogastroduodenoscopy exposed the development of esophageal varices, which were not observed preoperatively. The patient was diagnosed with decompensated liver cirrhosis accompanied by portal hypertension. This case strongly suggests that long-term follow-up after surgery may be required for patients with FC for screening of potential new bile duct stricture and progression to liver cirrhosis due to cholestasis.

Long-term Results of a Phase II Study of Neoadjuvant SOX for Advanced Gastric Cancer.

BACKGROUND/AIM: This study aimed to evaluate the long-term survival outcomes from our previous study: a phase II study of neoadjuvant chemotherapy with S-1 plus oxaliplatin for cT4 or N2-3 advanced gastric cancer. PATIENTS AND METHODS: The patients with clinical T4 and/or N2 or more lymph nodes received two cycles (3 weeks per cycle) of neoadjuvant chemotherapy with S-1 plus oxaliplatin (oxaliplatin at 130 mg/m2 on day 1 and S-1 at 80-120 mg/day on days 1 to 14), followed by gastrectomy with D2 lymphadenectomy. The final preplanned analysis of long-term outcomes, including overall and relapse-free survival, was performed. This trial has been completed and registered with the University Hospital Medical Information Network Clinical Trials Registry under number UMIN 000024656. RESULTS: Between May 2016 and March 2019, 30 patients were enrolled. All patients completed the protocol. After a median follow-up of 50 months for surviving patients, the 3-year overall and recurrence-free survival rates were 80.0% and 76.7%, respectively, at the last follow-up in March 2023, whereas the 5-year overall and recurrence-free survival rates were 72.7% and 73.0%, respectively. CONCLUSION: The administration of two cycles of neoadjuvant chemotherapy with S-1 plus oxaliplatin, followed by D2 gastrectomy, was associated with relatively good long-term oncologic outcomes for patients with high-risk gastric cancer.

Surgical outcome comparisons of multifocal IOLs of Lentis Comfort LS-313 MF15 and Tecnis Eyhance DIB00V.

AIM: To compare the surgical outcomes of a multifocal intraocular lens (IOL; Lentis Comfort LS-313 MF15) with those of an enhanced monofocal IOL (Tecnis Eyhance DIB00V). METHODS: This retrospective study included patients who underwent cataract surgery with LS-313 MF15 or Eyhance IOL implantation. Data regarding patient demographics, surgical records, and ophthalmic examination before the cataract surgery and one and three months postoperatively were collected. Visual acuities, refractive values, defocus curves, contrast sensitivities and subjective symptoms were evaluated. RESULTS: Among the 71 eyes (47 patients) included in this study, 32 eyes (20 patients) underwent LS-313 MF15 IOL implantation, and 39 eyes (27 patients) underwent Eyhance IOL implantation. No significant differences were observed in age, axial length, or refractive error between the two groups preoperatively. Furthermore, the distance-corrected and uncorrected distance visual acuities one month postoperatively did not differ between the groups, and both groups had sufficient visual acuities at the distances of 5, 1 m, 70, 50, and 30 cm. Other ophthalmic data, including subjective symptoms based on the 14-item Visual Function Index Questionnaire, monocular defocus curves, contrast sensitivities, and halo and glare, did not differ between the groups three months postoperatively. Moreover, both groups had good outcomes. The spherical equivalent one month postoperatively was significantly myopic in the LS-313 MF15 group compared with that in the Eyhance group (P=0.033); however, this difference was not observed three months postoperatively (P=0.471). CONCLUSION: Comparison of the surgical outcomes of LS-313 MF15 with those of Eyhance with different optical properties reveal that both IOLs show good postoperative outcomes, with no significant differences being noted between the two IOLs.

RHOMBUS DEFORMATION OF RETINAL LATERAL DISPLACEMENT AFTER EPIRETINAL MEMBRANE REMOVAL REVEALED BY DIFFEOMORPHIC IMAGE REGISTRATION.

PURPOSE: To establish an analysis method using diffeomorphic image registration and evaluate microvascular displacement through epiretinal membrane (ERM) removal. METHODS: Medical records of eyes that underwent vitreous surgery for ERM were reviewed. Postoperative optical coherence tomography angiography (OCTA) images were converted to the corresponding preoperative images according to a configured algorithm using diffeomorphism. RESULTS: Thirty-seven eyes with ERM were examined. Measured changes in the foveal avascular zone (FAZ) area showed a significant negative correlation with central foveal thickness (CFT). The average amplitude of microvascular displacement calculated for each pixel was 69 ± 27 µ m in the nasal area, which was relatively smaller than that in other areas. The vector map, which included both the amplitude and the vector of microvasculature displacement, showed a unique vector flow pattern called the rhombus deformation sign in 17 eyes. Eyes with this deformation sign showed less surgery-induced changes in the FAZ area and CFT and a milder ERM stage than those without this sign. CONCLUSION: The authors calculated and visualized microvascular displacement using diffeomorphism. The authors found a unique pattern (rhombus deformation) of retinal lateral displacement through ERM removal, which was significantly associated with the severity of ERM.

A nationwide certification system to increase the safety of highly advanced hepatobiliary-pancreatic surgery.

BACKGROUND: To ensure that highly advanced hepatobiliary-pancreatic surgery (HBPS) is performed safely, the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) board certification system for expert surgeons established a safety committee to monitor surgical safety. METHODS: We investigated postoperative mortality rates based on summary reports of numbers and outcomes of highly advanced HBPS submitted annually by the board-certified training institutions from 2012 to 2019. We also analyzed summary reports on mortality cases submitted by institutions with high 90-day post-HBPS mortality rates and recommended site visits and surveys as necessary. RESULTS: Highly advanced HBPS was performed in 121 518 patients during the 8-year period. Thirty-day mortality rates from 2012 to 2019 were 0.92%, 0.8%, 0.61%, 0.63%, 0.70%, 0.59%, 0.48%, and 0.52%, respectively (P < .001). Ninety-day mortality rates were 2.1%, 1.82%, 1.62%, 1.28%, 1.46%, 1.22%, 1.19%, and 0.98%, respectively (P < .001). Summary reports were submitted by 20 hospitals between 2015 and 2019. Mortality rates before and after the start of report submission and audit were 5.72% and 2.79%, respectively (odds ratio 0.690, 95% confidence interval 0.487-0.977; P = .037). CONCLUSIONS: Development of a system for designation of board-certified expert surgeons and safety management improved the mortality rate associated with highly advanced HBPS.

Correlation between higher-order aberration and photophobia after cataract surgery.

Cataract surgery impinges on the spatial properties and wavelength distribution of retinal images, which changes the degree of light-induced visual discomfort/photophobia. However, no study has analyzed the alteration in photophobia before and after cataract surgery or the association between retinal spatial property and photophobia. Here, we measured the higher-order aberrations (HOAs) of the entire eye and the subjective photophobia score. This study investigated 71 eyes in 71 patients who received conventional cataract surgery. Scaling of photophobia was based on the following grading system: when the patient is outdoor on a sunny day, score of 0 and 10 points were assigned to the absence of photophobia and the presence of severe photophobia prevents eye-opening, respectively. We decomposed wavefront errors using Zernike polynomials for a 3-mm pupil diameter and analyzed the association between photophobia scores and HOAs with Spearman's rank sum correlation (rs). We classified patients into two groups: photophobia (PP) unconcerned included patients who selected 0 both preoperatively or postoperatively and PP concerned included the remaining patients. After cataract surgery, photophobia scores increased, remained unchanged (stable), and decreased in 3, 41, and 27 cases, respectively. In the stable group, 35 of 41 cases belonged to PP unconcerned. In PP concerned, there were significant correlations between photophobia score and postoperative root-mean-square values of total HOAs (rs = 0.52, p = 0.002), total coma (rs = 0.52, p = 0.002), total trefoil (rs = 0.47, p = 0.006), and third-order group (rs = 0.53, p = 0.002). In contrast, there was no significant correlation between photophobia scores and preoperative HOAs. Our results suggest that the spatial properties of retinal image modified by HOAs may affect the degree of photophobia. Scattering light due to cataracts could contribute to photophobia more than HOAs, which may mask the effect of HOAs for photophobia preoperatively.

Intrahepatic Cholangiocarcinoma With Neither Intrahepatic Metastasis Nor Lymph Node Metastasis Is the Optimal Indication for Hepatectomy With Adjuvant Therapy.

Background/Aim: The optimal indication of hepatectomy with adjuvant therapy for intrahepatic cholangiocarcinoma (ICC) has not been evaluated in detail. Patients and Methods: We retrospectively studied 224 patients with ICC who underwent hepatectomy between 2000 and 2019. Prognostic factors for overall survival (OS) were evaluated by univariate and multivariate analysis. A total of 127 patients were treated with adjuvant therapy (62 patients with chemotherapy and 65 patients with immunotherapy) after hepatectomy, and 97 patients were treated with hepatectomy alone. Results: Intrahepatic metastasis (IM), lymph node metastasis (LNM) of ICC, adjuvant chemotherapy, and adjuvant immunotherapy were significant prognostic factors for OS on multivariate analysis. In 127 patients with neither IM nor LNM, the 5-year OS rate was significantly higher in 36 patients with adjuvant chemotherapy (81%) and in 34 patients with adjuvant immunotherapy (68%) than in 57 patients with hepatectomy alone (45%). Conclusion: The absence of IM or LNM is the optimal indication for hepatectomy with adjuvant therapy in patients with ICC.

Improved Mortality, Morbidity, and Long-Term Outcome After Anatomical Hepatectomy With the Glissonean Pedicle Approach in Patients With Hepatocellular Carcinoma: 30 Years' Experience at a Single Institute.

OBJECTIVE: We evaluated the morbidity and mortality after anatomical hepatectomy with the Glissonean pedicle approach, and long-term outcomes in relation to the morbidity in patients with hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: The mortality, morbidity, and long-term outcomes were evaluated retrospectively. METHODS: A total of 1953 patients with HCC underwent various anatomical hepatectomies with the Glissonean pedicle approach between 1985 and 2014. The mortality (30-day and 90-day) and morbidity (Clavien-Dindo class Ilia or higher) were evaluated among six 5-year eras (1985-1989, 1990-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2014). RESULTS: A total of 460 patients (24%) showed morbidity, and the overall 30-day and 90-day mortality rates were 1.8% and 3.3%, respectively. The 30-day (3.9%, 3.0%, 1.8%, 1.3%, 0.3%, 0.5%: P = 0.0074) and 90-day mortality (6.0%, 4.3%, 3.8%, 2.8%, 2.2%, 1.4%: P = 0.0445) significantly improved over the eras. Blood loss >2 L (odds ratio: 11.808, P = 0.0244) was an independent risk factor for 30-day mortality, and blood loss >2 L (odds ratio: 4.046, P = 0.0271) and bile leakage (odds ratio: 2.122, P = 0.0078) were independent risk factors for 90-day mortality on multivariate analysis. Morbidity was significant independent prognostic factors for overall survival (relative risk: 2.129, P < 0.0001) and recurrence-free survival (relative risk: 1.299, P < 0.0001) in patients with HCC. CONCLUSIONS: Anatomical hepatectomy with the Glissonean pedicle approach was achieved safely in patients with HCC. For more safety and longer survival, blood loss, bile leakage, and morbidity should be reduced. Longterm outcomes after anatomical hepatectomy with the Glissonean pedicle approach in patients with HCC have been improved over 30 years with gradually less mortality and morbidity due to decreases in blood loss >2 L and bile leakage.

Effectiveness of the Heads-Up Surgery System for Retinal Surgery in a Patient with Severe Photophobia.

BACKGROUND: The reported features and effectiveness of heads-up surgery (HUS) for ophthalmic surgery include greater resolution, teaching, and significantly reduced endoillumination power. OBJECTIVE: To report how to care for severe intraoperative photophobia using the HUS system during bilateral rhegmatogenous retinal detachment (RD) surgery in a patient with severe photophobia. CASE REPORT: A man in his 50s, who had been followed up for photophobia and visual impairment underwent five ophthalmic surgeries for bilateral RD. In his early 40s, he had been referred to our hospital because of a complaint of bilateral visual impairment, including severe photophobia, approximately 2 years prior. His decimal best-corrected visual acuities were 0.7 and 0.6 in his right and left eyes, respectively. Optical coherence tomography showed diffuse thinning of the entire retinal layer in the macula of both eyes, which was considered to be a cause of the decrement of visual acuity and photophobia. Twelve years after his first visit, he noticed multiple floaters in his left eye. For RD excluding the macular area, we planned cataract and retinal surgery under retrobulbar anesthesia. However, as we could not continue retinal surgery after cataract surgery due to severe photophobia, we performed general anesthesia (GA) during the second surgery. Seventeen months after the surgery, he underwent the third surgery for RD in his right eye under GA. For RD recurring twice, we performed surgery with the HUS system under retrobulbar anesthesia for the fourth and fifth surgeries, which avoided photophobia due to the significantly reduced light stimulation of the HUS system. CONCLUSION: Lower light intensity achieved by the HUS system enabled us to eliminate the patient's intraoperative discomfort. Consequently, we could perform the surgery under local anesthesia in this patient with RD who complained of severe photophobia that required GA using a conventional surgical system.

Phase II study of neoadjuvant chemotherapy with S-1 plus oxaliplatin for gastric cancer clinical T4 or N2-3.

In Japan, the standard treatment for stage II or III gastric cancer is D2 gastrectomy followed by administration of S-1 for one year. However, patients with stage III disease have unsatisfactory survival rates. The purpose of this study was to evaluate the efficacy and safety of neoadjuvant chemotherapy consisting of S-1 and oxaliplatin for advanced gastric cancer. Patients with cT4 or cN2-3 gastric cancer were scheduled to receive two courses of chemotherapy (130 mg/m2 oxaliplatin on Day 1, 80 mg/m2 S-1 per day twice daily for 14 days) followed by surgery. The primary endpoint was the R0 resection rate. The secondary endpoints were rates of completion of protocol treatment, pathological response, and adverse events; and 3-year overall survival, 5-year overall survival, and 5-year recurrence-free survival. Between May 2016 and March 2019, 30 patients were enrolled in the study, all of whom completed the protocol treatment. The R0 resection rate (primary endpoint) was 93.3% (95% confidence interval: 77.9-99.2). The pathological response rate was 63.3%. Grade 3-4 toxicities included anemia (3.3%), anorexia (6.7%), and fatigue (3.3%). Relative dose intensities were 91.2% and 94.2% for S-1 and oxaliplatin, respectively. Neoadjuvant S-1 and oxaliplatin is highly effective, achieving an acceptable R0 resection rate with relatively few severe toxicities and good compliance.Trial registration: Registry name: A prospective intervention study on the availability of preoperative SOX therapy for T4 or N2-3 gastric cancer. Trial ID: UMIN: UMIN000024656. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R00002836.

Association of meteorological factors with the frequency of primary rhegmatogenous retinal detachment in Japan.

This 5-year ecological study assessed the association between meteorological factors and rhegmatogenous retinal detachment (RRD) frequency in 571 eyes of 543 cases of primary RRD at the Jikei University Kashiwa Hospital, Japan. We examined the monthly and seasonal distributions of RRD frequency using one-way analysis of variance. We then evaluated the relationship between monthly RRD frequency and 36 meteorological parameters using Poisson regression analysis. Furthermore, we developed multivariate regression models to predict the frequency of RRD based on specific meteorological parameters. There were no significant differences in the monthly and seasonal distributions (monthly, P = 0.99; seasonal, P = 0.77). The following eight parameters were associated with a lower RRD frequency: average sea level barometric pressure and average daily variation of average temperature, maximum temperature, maximum wind speed, maximum instantaneous wind speed, humidity, average sea level barometric pressure, and minimum sea level barometric pressure (P < 0.05). The best model to predict RRD frequency showed sufficient validity (Akaike's information criterion with correction for small sample size = 332.0) and predictive power (proportion of variance explained by cross-validation method = 84.82%, 95% CI 72.18-93.72). In conclusion, low atmospheric pressure and high meteorological stability are significantly associated with a higher frequency of RRD. In addition, the Poisson regression analysis showed sufficient validity and predictability for predicting RRD frequency.

The first Japanese family of CDH3-related hypotrichosis with juvenile macular dystrophy.

BACKGROUND: Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive inherited disorder caused by biallelic variants in the CDH3 gene encoding P-cadherin. Here, we report two Japanese sibling patients with HJMD. METHODS: Whole-exome sequencing (WES) was performed to identify disease-causing variants. In addition, ophthalmic and dermatological examinations were performed to classify the phenotype of each patient. RESULTS: The WES analysis revealed novel compound heterozygous CDH3 variants [c.123_129dupAGGCGCG (p.Glu44fsX26) and c.2280+1G>T] in both patients; the unaffected, nonconsanguineous parents each exhibited one of the variants. Both patients showed the same clinical findings. Ophthalmologically, they exhibited progressive loss of visual acuity and chorioretinal macular atrophy, as examined with fundoscopy, fundus autofluorescence imaging, and optical coherence tomography. Full-field electroretinography, assessing generalized retinal function, revealed nearly normal amplitudes of both rod- and cone-mediated responses. Multifocal electroretinography, reflecting macular function, showed extremely decreased responses in the central area, corresponding to the chorioretinal atrophy. Dermatological examination revealed diffuse thinning of the scalp hair, which was sparse and fragile. CONCLUSION: This is the first report of Japanese patients with HJMD and novel compound heterozygous truncating variants in CDH3. Our findings can expand the knowledge and understanding of CDH3-related HJMD, which could be helpful to ophthalmologists and dermatologists.

PARACENTRAL ACUTE MIDDLE MACULOPATHY AFTER ENDOVASCULAR COIL EMBOLIZATION.

PURPOSE: To describe two cases of paracentral acute middle maculopathy (PAMM) that occurred unilaterally after endovascular coil embolization. METHODS: Medical records including ophthalmic examinations of two PAMM cases were retrospectively reviewed. RESULTS: The first case was a 64-year-old woman with hyperlipidemia and chronic sinusitis. The second case was a 49-year-old man with hypertension, hyperlipidemia, tension headache, and vertigo. Both cases exhibited paracentral scotomas just after endovascular coil embolization. Ophthalmoscopy showed multiple faint white-yellow lesions in each affected eye. Optical coherence tomography showed hyper-reflective bands that were mainly observed in the inner nuclear layer and corresponded to the PAMM lesions. Optical coherence tomography angiography revealed variable degrees of abnormal vasculature from slight dilation, decreased visualization, to nonvisualization in the superficial capillary plexuses and similar capillary changes in deep capillary plexuses. CONCLUSION: We described two cases with PAMM that occurred after endovascular coil embolization, which was a new precursor cause of PAMM. Our results demonstrate that optical coherence tomography angiography is especially useful for not only diagnosis, but also for follow-up evaluations in patients with PAMM.

SEVERE RECURRENT FIBROVASCULAR PROLIFERATION AFTER COMBINED INTRAVITREAL BEVACIZUMAB INJECTION AND LASER PHOTOCOAGULATION FOR AGGRESSIVE POSTERIOR RETINOPATHY OF PREMATURITY.

PURPOSE: To describe the clinical features of severe recurrent fibrovascular proliferation after intravitreal bevacizumab injections and laser photocoagulation for aggressive posterior retinopathy of prematurity. METHODS: This retrospective, nonrandomized case series reviewed the medical and ophthalmic records in the referral hospital and our hospital. PATIENTS: Four patients (seven eyes) with aggressive posterior retinopathy of prematurity. RESULTS: The patients were referred for vitrectomy with/without lensectomy for recurrent fibrovascular proliferation with a tractional retinal detachment after combined intravitreal bevacizumab injections and laser photocoagulation. Three patients were born at 22 weeks or 23 weeks' gestational age and one patient at 29 weeks' gestational age. Preoperatively, fluorescein angiography images showed all eyes had tractional retinal detachment from regrowth of fibrovascular proliferation 3 months to 5 months after the intravitreal bevacizumab injection and abnormal retinal vasculature; four eyes had a broad ischemic retina. Postoperatively, four eyes had retinal attachment and three eyes a total retinal detachment. Neovascular glaucoma developed in five of the seven eyes during the clinical course. CONCLUSION: Severe fibrovascular proliferation may recur due to widespread retinal ischemia with capillary dropout and abnormal vasculature after failed combined intravitreal bevacizumab and laser photocoagulation therapy as the initial treatment for aggressive posterior retinopathy of prematurity. Careful follow-up is important especially after anti-vascular endothelial growth factor treatment, with recognition that severe reactivation is possible.

Structure of the Retinal Margin and Presumed Mechanism of Retinal Detachment in Choroidal Coloboma.

PURPOSE: To describe the vitreoretinal structure at the margin of the choroidal coloboma in infants and older patients using swept-source (SS) OCT. DESIGN: Retrospective case series. PARTICIPANTS: Nineteen eyes of 16 patients with choroidal coloboma (7 males, 9 females; average age, 12.3 ± 7.1 years). METHODS: The patients were classified into 2 groups: infants 1 year of age or younger (3 eyes) and older patients (16 eyes). Each finding on SS OCT was documented according to previously defined histopathologic findings. MAIN OUTCOME MEASURES: Description of the SS OCT features of choroidal colobomas. RESULTS: Swept-source OCT showed that the extracolobomatous retina centrally traversed the margin to continue as the marginal intercalary membrane (MICM), whereas the outer layers of the MICM were reversed at the point (point of reversal [POR]). The expected duplication was seen in all infant eyes, but in none of the older eyes whose outer layers of the MICM were ambiguous. However, at the boundary between the layered MICM and monolayered central intercalary membrane (CICM), the POR was detectable in all patients. Further SS OCT analysis showed that the MICM schisis and CICM schisis occurred simultaneously with vitreous traction. Retinal detachments (RDs) seen in 4 eyes were connected to the only MICM schisis, and a MICM break was identified in 1 eye. Swept-source OCT showed that retinal pigment epithelial hyperplasia adhered tightly to the retina and that the glial triangle was adhered tightly to the sclera, indicating barriers to the development of RD after MICM schisis. CONCLUSIONS: Swept-source OCT first visualized the POR in infant eyes and showed that the POR was identifiable despite the atrophic changes in the outer layer of the MICM in the older eyes. Based on the POR location, we confirmed that the intercalary membranes reported in previous OCT studies were clearly differentiated between the MICM and CICM. We also showed that the presence of MICM and CICM schisis resulted from vitreous traction at the coloboma margin and that MICM breaks induced RD only if the barrier that prevented the development of RD was broken.

Progress of macular atrophy during 30 months' follow-up in a patient with spinocerebellar ataxia type1 (SCA1).

PURPOSE: To report the 30-months' course of macular dystrophy in a patient with genetically confirmed spinocerebellar ataxia type1 (SCA1). METHODS: Detailed ophthalmological examinations including best-corrected visual acuity (BCVA), perimetry, multimodal fundus imaging, and electrophysiological recordings were performed on a 52-year-old woman with SCA1. The number of CAG sequence repeats of the candidate gene was verified. RESULTS: The baseline decimal BCVA was 0.2 OD and 0.3 OS. Goldman perimetry showed relative central scotomas and slight enlargements of Mariotte blind spot bilaterally. Ophthalmoscopy revealed no abnormalities in the macula and optic disk. Fundus autofluorescence (FAF) showed a circular hyperautofluorescence and round-shaped hypoautofluorescence in the macula. Optical coherence tomography (OCT) showed a loss of the interdigitation zone and ellipsoid zone (EZ) in the macula. Full-field scotopic and photopic Full-field electroretinograms (ERGs) were normal, and multifocal ERGs were decreased in the central area. After 30 months, the BCVA had not changed, but the FAF showed a spark-like hypoautofluorescence in the macula. The abnormal area of the EZ had expanded toward the periphery, and the rate of EZ loss was 199.7%/year OD and 206.8%/year OS. Genetic examinations revealed an increase in the number of heterozygous CAG repeats in the ATXN1 gene, and the CAG repeat number of the mutant allele ranged from 43 to 48. CONCLUSIONS: The full-field scotopic and photopic ERGs were normal. The mfERGs were significantly smaller in the central region. OCT demonstrated bilateral photoreceptor atrophy in the macula, and the rate of EZ loss was more rapid than in other macular dystrophies. Spark-like hypoautofluorescence appeared during the course of the disease process which might be a specific feature of SCA1-related retinopathy.

Early hemodynamics of hepatocellular carcinoma using contrast-enhanced ultrasound with Sonazoid: focus on the pure arterial and early portal phases.

To clarify the early hemodynamics of hepatocellular carcinoma (HCC), we defined the early portal phase of contrast-enhanced ultrasound (CEUS) and examined the reliability of this modality for determining HCC differentiation. Starting in 2007, we performed Sonazoid CEUS in 146 pathologically confirmed hepatic nodules; 118 HCC (8 poorly [Pd], 73 moderately [Md] and 37 well-differentiated [Wd]) and 28 benign nodules. We focused on the pure arterial and early portal phases up to 45 seconds after Sonazoid injection, and then the subsequent phase up to 30 minutes. We calculated covariance-adjusted sensitivities for nodule enhancement combinations of these three phases. Nodule enhancements were divided into hypo, iso and hyper. A positive predictive value of 100% was obtained for the following patterns: iso-iso-hypo, hypo-iso-iso, and hypo-hypo-hypo for Wd, hyper-iso-hypo and hyper-hypo-hypo for Md, hypo-hyper-hypo for Pd, and hyper-hyper-hyper for benign nodules. In Wd HCC (early HCC), there were seven enhancement patterns, thought to be characterized by various hemodynamic changes from early to advanced HCC. Two patterns allowing a diagnosis of Wd HCC were hypo in the pure arterial phase. Subsequent iso-enhancement in the early portal phase indicated a portal blood supply. Decreased enhancement in the early portal phase allows a diagnosis of Md HCC. However, gradual enhancement observed from the pure arterial to the early portal phase allows a diagnosis of Pd HCC. Therefore, even in the early portal phase, hemodynamic changes were visible not only in Wd but also in Md and Pd HCC. In conclusion, with division of the early phase hemodynamics into pure arterial and early portal phases, CEUS can provide information useful for determining the likely degree of HCC differentiation and for distinguishing early stage HCC from benign nodules.

Unique and progressive retinal degeneration in a patient with cancer associated retinopathy.

PURPOSE: To report clinical course of a patient with cancer-associated retinopathy (CAR) medicated by steroid therapy, focusing on retinal degeneration progression. OBSERVATIONS: A 67 years-old female patient, who had a surgical history of endometrial carcinoma with adjuvant chemotherapy, was referred to our hospitals for the complaints of sudden reduced visual acuity and visual field constriction in the right eye. Best corrected visual acuity (BCVA) was 0.4 and 1.0 in right and left eyes, respectively. Funduscopy showed almost normal appearance in both eyes. Fluorescein angiography showed slight fluorescein leakage from the optic disc in both eyes and an inferior arcade vessel in the right eye. Optical coherence tomography (OCT) images showed loss of ellipsoid zone (EZ) and thinning of outer retinal layers at the nasal area of the fovea in both eyes. Goldmann perimetry (GP) demonstrated several paracentral absolute scotomas with peripheral visual field constriction in the right eye, and a paracentral relative scotoma with preserved peripheral visual field in the left eye. Ten months after the first visit, retinopathy progressed in both eyes. Funduscopy indicated mild retinal degeneration along with arcade veins with white sheathing of retinal arteries. Slightly visible EZ at the fovea and loss of EZ and interdigitation zone and thinning of outer retinal layers at other areas were observed in OCT images from both eyes. GP showed no response in both eyes. Oral prednisolone therapy was started and gradually tapered over a 3-month period. Twelve and fifteen months after the first visit, BCVA, EZ at the fovea in OCT images, and visual field gradually improved, whereas retinal degeneration along arcade veins became apparent. CONCLUSIONS AND IMPORTANCE: We reported a patient with CAR who exhibited progressive retinal degeneration and good response to oral prednisolone therapy. This case expands the clinical spectrum of CAR.

Clinical and genetic characteristics of 10 Japanese patients with PROM1-associated retinal disorder: A report of the phenotype spectrum and a literature review in the Japanese population.

Variants in the PROM1 gene are associated with cone (-rod) dystrophy, macular dystrophy, and other phenotypes. We describe the clinical and genetic characteristics of 10 patients from eight Japanese families with PROM1-associated retinal disorder (PROM1-RD) in a nationwide cohort. A literature review of PROM1-RD in the Japanese population was also performed. The median age at onset/examination of 10 patients was 31.0 (range, 10-45)/44.5 (22-73) years. All 10 patients showed atrophic macular changes. Seven patients (70.0%) had spared fovea to various degrees, approximately half of whom had maintained visual acuity. Generalized cone (-rod) dysfunction was demonstrated in all nine subjects with available electrophysiological data. Three PROM1 variants were identified in this study: one recurrent disease-causing variant (p.Arg373Cys), one novel putative disease-causing variant (p.Cys112Arg), and one novel variant of uncertain significance (VUS; p.Gly53Asp). Characteristic features of macular atrophy with generalized cone-dominated retinal dysfunction were shared among all 10 subjects with PROM1-RD, and the presence of foveal sparing was crucial in maintaining visual acuity. Together with the three previously reported variants [p.R373C, c.1551+1G>A (pathogenic), p.Asn580His (likely benign)] in the literature of Japanese patients, one prevalent missense variant (p.Arg373Cys, 6/9 families, 66.7%) detected in multiple studies was determined in the Japanese population, which was also frequently detected in the European population.

Clinical and Genetic Characteristics of 15 Affected Patients From 12 Japanese Families with GUCY2D-Associated Retinal Disorder.

Purpose: To determine the clinical and genetic characteristics of patients with GUCY2D-associated retinal disorder (GUCY2D-RD). Methods: Fifteen patients from 12 families with inherited retinal disorder (IRD) and harboring GUCY2D variants were ascertained from 730 Japanese families with IRD. Comprehensive ophthalmological examinations, including visual acuity (VA) measurement, retinal imaging, and electrophysiological assessment were performed to classify patients into three phenotype subgroups; macular dystrophy (MD), cone-rod dystrophy (CORD), and Leber congenital amaurosis (LCA). In silico analysis was performed for the detected variants, and the molecularly confirmed inheritance pattern was determined (autosomal dominant/recessive [AD/AR]). Results: The median age of onset/examination was 22.0/38.0 years (ranges, 0-55 and 1-73) with a median VA of 0.80/0.70 LogMAR units (ranges, 0.00-1.52 and 0.10-1.52) in the right/left eye, respectively. Macular atrophy was identified in seven patients (46.7%), and two had diffuse fundus disturbance (13.3%), and six had an essentially normal fundus (40.0%). There were 11 patients with generalized cone-rod dysfunction (78.6%), two with entire functional loss (14.3%), and one with confined macular dysfunction (7.1%). There were nine families with ADCORD, one with ARCORD, one with ADMD, and one with ARLCA. Ten GUCY2D variants were identified, including four novel variants (p.Val56GlyfsTer262, p.Met246Ile, p.Arg761Trp, p.Glu874Lys). Conclusions: This large cohort study delineates the disease spectrum of GUCY2D-RD. Diverse clinical presentations with various severities of ADCORD and the early-onset severe phenotype of ARLCA are illustrated. A relatively lower prevalence of GUCY2D-RD for ADCORD and ARLCA in the Japanese population was revealed. Translational Relevance: The obtained data help to monitor and counsel patients, especially in East Asia, as well as to design future therapeutic approaches.