Three-year outcome of photodynamic therapy combined with VEGF inhibitor for pachychoroid neovasculopathy.

BACKGROUND: Long-term results of photodynamic therapy (PDT) combined with vascular endothelial growth factor (VEGF) inhibitors for pachychoroid neovasculopathy (PNV) are not yet clear. METHODS: This study is a retrospective, observational case series. We retrospectively examined untreated PNV cases (22 cases, 22 eyes, mean age of 71.0 years) who underwent PDT therapy in combination with VEGF inhibitors followed by additional treatments with pro re nata protocol. Visual acuity, number of treatments, and time to recurrence were examined. In addition, foveal choroidal thickness and choroidal vascularity index (CVI) were evaluated in 13 of 22 patients who were followed up with SpectralisOCTR from baseline. RESULTS: Fifteen (68%) cases had polyps at baseline. LogMAR visual acuity averaged 0.24 ± 0.20 (range, - 0.079 to 0.82) at baseline and significantly improved after 1, 2, and 3 years (p = 0. 004, 0.0003, 0.002, respectively). Fourteen patients (64%) recurred, with an average time to recurrence of 1.8 ± 0.9 years. Foveal choroidal thickness decreased significantly after 1 year (average from 326 µm to 263 µm) and remained unchanged up to 3 years (255 µm). CVI also decreased after 1 year (average from 0.62 to 0.61) and remained unchanged until 3 years later (0.60). CONCLUSIONS: We examined the 3-year course of PDT in combination with the VEGF inhibitor for untreated PNV. Visual acuity was improved, foveal choroidal thickness and CVI were decreased after 3 years.

Perioperative Management of Spinal Arteriovenous Malformation Embolization: Delayed Venous Thrombosis and Implications for Severe Back Pain.

BACKGROUND AND PURPOSE: The prognosis of untreated spinal arteriovenous malformations (SAVMs) is poor. Embolization plays an important role in the management of intramedullary SAVMs. Delayed aggravation due to spinal venous thrombosis following successful embolization has been reported; however, perioperative management strategies to prevent thrombosis have not been explored. We present our single-center experience of SAVM embolization and perioperative management, including anticoagulation. MATERIAL AND METHODS: We retrospectively evaluated 18 patients with SAVMs who underwent transarterial embolization. Perioperative anticoagulation therapy was administered to selected patients. We compared the characteristics of the patients, including perioperative management procedures, between those with and without postoperative worsening following embolization. RESULTS: Acute postoperative worsening within 1 week occurred in 4 (22.2%) patients. Of these, immediate worsening was observed in one patient as a procedure-related complication. Delayed worsening after 24 h was observed in 3 patients, caused by delayed venous thrombosis with severe back pain. Rescue anticoagulation for delayed worsening improved symptoms in two patients. A comparison between patients with and without acute postoperative worsening revealed significant differences in age (median 46.5 vs. 26.5 years, p = 0.009) and the presence of postoperative back pain (75.0% vs. 0%, p = 0.005); however, there was no significant difference in use of selective anticoagulation (p = 0.274). CONCLUSION: The results of this study suggest that SAVM embolization can cause acute worsening due to postoperative venous thrombosis with severe back pain, which may be reversed by anticoagulation therapy. Back pain is an important finding that suggests venous thrombosis, and anticoagulation should be urgently administered.

Comparison of efficacy between clazosentan and fasudil hydrochloride-based management of vasospasm after subarachnoid hemorrhage focusing on older and WFNS grade V patients: a single-center experience in Japan.

Subarachnoid hemorrhage often leads to poor outcomes owing to vasospasm, even after successful aneurysm treatment. Clazosentan, an endothelin receptor inhibitor, has been proven to be an effective treatment for vasospasms in a Japanese randomized controlled trial. However, its efficacy in older patients (≥ 75 years old) and those with World Federation of Neurosurgical Societies (WFNS) grade V has not been demonstrated. We retrospectively evaluated the efficacy of clazosentan in older patients and those with WFNS grade V, using real-world data. Patients with subarachnoid hemorrhage treated before and after the introduction of clazosentan were retrospectively evaluated. The patients were categorized into two groups (clazosentan era versus pre-clazosentan era), in which vasospasm management and outcomes were compared. Vasospasms were managed with fasudil hydrochloride-based (pre-clazosentan era) or clazosentan-based treatment (clazosentan era). Seventy-eight patients were included in this study: the clazosentan era (n = 32) and pre-clazosentan era (n = 46). Overall, clazosentan significantly reduced clinical vasospasms (clazosentan era: 31.3% versus pre-clazosentan era: 60.9%, p = 0.01), delayed cerebral ischemia (DCI) (9.4% versus 39.1%, p = 0.004), and vasospasm-related morbidity and mortality (M/M) (3.1% versus 19.6%, p = 0.03). In subgroup analysis of older patients or those with WFNS grade V, no significant difference was observed in clinical outcomes, although both DCI and vasospasm-related M/M were lower in the clazosentan era. Clazosentan was more effective than fasudil-based management in preventing DCI and reducing vasospasm-related M/M. Clazosentan could be used safely in older patients and those with WFNS grade V, although clinical outcomes in these patients were comparable to those of conventional treatment.

Mound-like Epiretinal Material: Its Short-term Changes and Association with Posterior Vitreous Detachment.

PURPOSE: To describe clinical characteristics of a retinal finding termed mound-like epiretinal material (MOLEM), and distinguish it from epiretinal proliferation, a similar epiretinal finding previously described in various pathologies. METHODS: Five eyes from five patients were retrospectively identified from medical records. Clinical findings and images, including fundus photographs and optical coherence tomography (OCT), were reviewed. RESULTS: All eyes displayed mound-like material with uniform and low-to-moderate reflectivity on an otherwise intact retinal surface detected on OCT. No eyes presented with concurrent pathology typically observed in cases of epiretinal proliferation, such as lamellar/full-thickness macular hole, epiretinal membrane, vitreomacular traction, or uveitis. Two eyes exhibited central serous chorioretinopathy, but there was no association of MOLEM with serous retinal detachment. In three out of five eyes, MOLEM appeared simultaneously with posterior vitreous detachment (PVD). Some lesions underwent irregular transformations over months and occasionally disappeared. While all cases were monitored without intervention, no visual decline or complications attributed to MOLEM were detected. CONCLUSION: MOLEM represents a novel clinical finding, characterized by transient morphological changes without symptoms and potential association with PVD. It may occur in eyes lacking macular diseases linked with epiretinal proliferation, a similar yet distinct lesion. The incidence, etiology, and clinical significance of MOLEM warrant further investigation by accumulating comparable cases, although the lesion appears benign and self-limiting.

Dosimetric evaluation in Helical TomoTherapy for lung SBRT using Monte Carlo-based independent dose verification software.

PURPOSE: To elucidate the dosimetric errors caused by a model-based algorithm in lung stereotactic body radiation therapy (SBRT) with Helical TomoTherapy (HT) using Monte Carlo (MC)-based dose verification software. METHODS: For 38 plans of lung SBRT, the dose calculation accuracy of a treatment planning system (TPS) of HT was compared with the results of DoseCHECK, the commercial MC-based independent verification software. The following indices were extracted to evaluate the correlation of dosimetric errors: (1) target volume, (2) average computed tomography (CT) value of the planning target volume (PTV) margin, and (3) average CT value of surrounding 2-mm area of the PTV (PTV ring). Receiver operating characteristic (ROC) analyses determined the threshold for 5% of differences in PTV D95%. Then, the 38 plans were classified into two groups using the cutoff values of ROC analysis for these three indices. Dosimetric differences between groups were statistically compared using the Mann-Whitney U test. RESULTS: TPS of HT overestimated by more than 5% in the PTV D95% in 16 of 38 plans. The PTV ring showed the strongest correlation with dosimetric differences. The cutoff value for the target volume, the PTV margin, and the PTV ring was 14.7 cc, -754 HU, and -708 HU, respectively. The area under the curve (AUC) for the target volume, the PTV margin, and the PTV ring were 0.835, 0.878, and 0.932, respectively. Dosimetric errors more than 5% were observed when the PTV volume was less than 15 cc or when the CT value around the target was less than -700 HU. CONCLUSION: The TPS of HT might overestimate the PTV dose by more than 5% if any the three indices in this study were below threshold. Therefore, independent verification with an MC-based algorithm should be strongly recommended for lung SBRT in HT.

Intravitreal anti-vascular endothelial growth factor and combined photodynamic therapy for pachychoroid neovasculopathy: long-term treatment outcomes.

PURPOSE: To examine the long-term visual outcomes after initial treatment with combined photodynamic therapy (PDT) or aflibercept treat-and-extend (TAE) monotherapy in patients with pachychoroid neovasculopathy (PNV). METHODS: Patients diagnosed with PNV, initially treated with PDT combined with anti-vascular endothelial growth factor (VEGF) or intravitreal aflibercept (IVA) monotherapy in the TAE protocol and followed up for at least 6 months, were included in the study. Medical records were retrospectively reviewed. Survival analysis was performed, in which deterioration in logMAR visual acuity by 0.1 or 0.3 is defined as "death." The annual number of treatments was also analyzed. Sub-analysis was performed on 33 patients diagnosed with PNV without polypoidal lesions. RESULTS: This study included 46 patients (23 in the initial combined PDT group and 23 in the IVA TAE group). Mean age, sex, mean baseline logMAR visual acuity, or duration of observation (3.6 ± 3.2 years vs. 3.1 ± 1.9 years) in both groups were comparable. As for visual outcome, no significant differences were found in survival analysis based on worsening of 0.1 or 0.3 logMAR (3-year survival; 26% vs. 26%, 91% vs. 90%, respectively). Meanwhile, the additional number of anti-VEGF injections per year was significantly lower in the initial combined PDT group than in the IVA TAE group (1.0 ± 1.3 vs. 4.1 ± 1.5, p < 0.0001). No significant differences were found in the number of additional PDTs per year (0.07 ± 0.20 vs. 0.02 ± 0.09, p = 0.27). Similar results were found in a sub-analysis of 33 patients without polyps. CONCLUSION: In the treatment of PNV, regardless of the presence of polyps, the long-term visual outcomes were similar between the initial combined PDT and IVA TAE monotherapy. However, the annual number of anti-VEGF injections was lower in the initial combined PDT group than in the aflibercept TAE group, whereas that of PDT was comparable.

Biomechanical properties measured with dynamic Scheimpflug analyzer in central serous chorioretinopathy.

PURPOSE: Recent evidence suggests that venous congestion at the vortex vein significantly contributes to the development of central serous chorioretinopathy (CSCR), and sclera is observed to be thicker in affected eyes. This study aims to investigate whether eyes with CSCR exhibit stiff corneas, measured using Corneal Visualization Scheimflug Technology (Corvis ST), which may serve as an indicator of scleral stiffness. METHODS: This retrospective case-control study comprises 52 eyes from 33 patients diagnosed with CSCR and 52 eyes from 32 normal controls without CSCR. We compared biomechanical parameters measured with Corvis ST and anterior scleral thickness measured using anterior segment swept-source optical coherence tomography between the two groups. RESULTS: Age, sex, axial length, intraocular pressure, and central corneal thickness showed no significant differences between the two groups (p > 0.05, linear mixed model). Three biomechanical parameters-peak distance, maximum deflection amplitude, and integrated inverse radius-indicated less deformability in CSCR eyes compared to control eyes. The stress-strain index (SSI), a measure of stiffness, and anterior scleral thickness (AST) at temporal and nasal points were significantly higher in the CSCR eyes. SSI and AST were not correlated, yet both were significantly and independently associated with CSCR in a multivariate logistic regression model. CONCLUSIONS: Eyes affected by CSCR have stiffer corneas, irrespective of thicker scleral thickness. This suggests that stiffer sclera may play a role in the pathogenesis of CSCR.

Functional characterization of variants found in Japanese patients with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant form of vascular dysplasia. Genetic diagnosis is made by identifying loss-of-function variants in genes, such as ENG and ACVRL1. However, the causal mechanisms of various variants of unknown significance remains unclear. In this study, we analyzed 12 Japanese patients from 11 families who were clinically diagnosed with HHT. Sequencing analysis identified 11 distinct variants in ACVRL1 and ENG. Three of the 11 were truncating variants, leading to a definitive diagnosis, whereas the remaining eight were splice-site and missense variants that required functional analyses. In silico splicing analyses demonstrated that three variants, c.526-3C > G and c.598C > G in ACVRL1, and c.690-1G > A in ENG, caused aberrant splicing, as confirmed by a minigene assay. The five remaining missense variants were p.Arg67Gln, p.Ile256Asn, p.Leu285Pro, and p.Pro424Leu in ACVRL and p.Pro165His in ENG. Nanoluciferase-based bioluminescence analyses demonstrated that these ACVRL1 variants impaired cell membrane trafficking, resulting in the loss of bone morphogenetic protein 9 (BMP9) signal transduction. In contrast, the ENG mutation impaired BMP9 signaling despite normal cell membrane expression. The updated functional analysis methods performed in this study will facilitate effective genetic testing and appropriate medical care for patients with HHT.

Peripapillary vessel density in eyes with cone-rod dystrophy.

PURPOSE: To compared the vessel density (VD) around the optic nerve head (ONH) in eyes with cone-rod dystrophy (CORD) and healthy control eyes in a sector-wise manner and to investigate the relationship between VD around the ONH and visual function in CORD eyes. METHODS: Twenty-six eyes in 14 CORD patients and 25 eyes in 25 healthy control subjects were examined. Using OCT angiography images, the VDs in the superficial and deep capillary plexus at the macula (sVDm and dVDm) and those around the ONH in the superior, temporal, inferior and nasal region (VDnh_s, VDnh_t, VDnh_i, and VDnh_n, respectively) were measured for each eye. Patient age, visual acuity (VA) and VDs were then compared between two groups. Moreover, the relationships between VA and the VDs were analyzed using a linear mixed model and AICc model selection. RESULTS: No significant difference in age was seen between the CORD and control groups (p = 0.87, Wilcoxon rank sum test), but the VA was significantly lower in the CORD group (p<0.0001). Both sVDm and dVDm were significantly lower in the CORD eyes than in the control eyes (both p<0.0001). Among VDnh_s, VDnh_t, VDnh_i, and VDnh_n, however, only VDnh_t differed significantly between the CORD and control groups (p = 0.035). Among age, VDnh_t, dVDm, and sVDm, the optimal model for VA included only VDnh_t and dVDm. CONCLUSIONS: In addition to the VD in the deep capillary plexus at the macula, the measurement of temporal VD around the ONH might be useful for predicting visual function in eyes with CORD.

Dosimetric comparison of four-dimensional computed tomography based internal target volume against variations in respiratory motion during treatment between volumetric modulated arc therapy and three-dimensional conformal radiotherapy in lung stereotactic body radiotherapy.

This study focused on the dosimetric impact of variations in respiratory motion during lung stereotactic body radiotherapy (SBRT). Dosimetric comparisons between volumetric modulated arc therapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) were performed using four-dimensional computed tomography (4DCT)-based internal target volumes (ITV). We created retrospective plans for ten patients with lung cancer who underwent SBRT using 3DCRT and VMAT techniques. A Delta4 Phantom + (ScandiDos, Uppsala, Sweden) was used to evaluate the dosimetric robustness of 4DCT-based ITV against variations in respiratory motion during treatment. We analyzed respiratory motion during treatment. Dose-volume histogram parameters were evaluated for the 95% dose (D95%) to the planning target volume (PTV) contoured on CT images obtained under free breathing. The correlations between patient respiratory parameters and dosimetric errors were also evaluated. In the phantom study, the average PTV D95% dose differences for all fractions were - 2.9 ± 4.4% (- 16.0 - 1.2%) and - 2.0 ± 2.8% (- 11.2 - 0.7%) for 3DCRT and VMAT, respectively. The average dose difference was < 3% for both 3DCRT and VMAT; however, in 5 out of 42 fractions in 3DCRT, the difference in PTV D95% was > 10%. Dosimetric errors were correlated with respiratory amplitude and velocity, and differences in respiratory amplitude between 4DCT and treatment days were the main factors causing dosimetric errors. The overall average dose error of the PTV D95% was small; however, both 3DCRT and VMAT cases exceeding 10% error were observed. Larger errors occurred with amplitude variation or baseline drift, indicating limited robustness of 4DCT-based ITV.

Comparison of functional and morphologic changes between brolucizumab and faricimab in neovascular age-related macular degeneration.

PURPOSE: This study aimed to compare functional and morphologic changes in the loading phase between patients with treatment-naïve macular neovascularization (MNV) due to neovascular age-related macular degeneration (nAMD) treated with either intravitreal brolucizumab (IVBr) or intravitreal faricimab (IVF) injections in a clinical setting. METHODS: We retrospectively studied 92 consecutive eyes of 90 patients with neovascular nAMD who were scheduled to receive IVBr (42 eyes of 41 patients) or IVF (50 eyes of 49 patients) injections between October 2021 and December 2022. All patients received three consecutive monthly injections of 6.0 mg/0.05 mL brolucizumab or 6.0 mg/0.05 mL faricimab. The best-corrected visual acuity (BCVA), central foveal thickness (CFT), and central choroidal thickness (CCT) at baseline and 1, 2, and 4 months after the initial treatment were measured and compared between the groups. RESULTS: Thirty-seven eyes in IVBr group and forty-seven eyes in IVF group who finished treatments in the loading phase were assessed at the follow-up examination. The BCVA, CFT, and CCT changed significantly after loading phase in both groups (P < 0.05 for both comparisons). The IVBr group had more rapid improvement of the BCVA (P = 0.037) at 1 month than the IVF group, but there was no difference at 4 months (P = 0.367). The CFT and CCT decreases tended to be greater in the IVBr group than in the IVF group throughout the follow-up period. Of the five eyes excluded from the IVBr group, one eye (2.4%) each had intraocular inflammation (IOI) and was a non-responder, and two eyes (4.8%) had retinal pigment epithelial tears after treatment. Of the three eyes excluded from the IVF group, two eyes (4.0%) did not respond to the treatment. CONCLUSIONS: Both IVBr and IVF injections were well-tolerated and improved the VA in treatment-naïve patients with MNV due to nAMD after a loading phase, although IVBr caused a trend toward faster visual improvements in the BCVA. The IVBr group also had greater reductions of the CFT and CCT than the IVF group. However, the potential for adverse events and no response to treatment with each drug are considerations.

Comparing Efficacy Between Robust and PTV Margin-based Optimizations for Interfractional Anatomical Variations in Prostate Tomotherapy.

BACKGROUND/AIM: Interfractional anatomical variations cause considerable differences between planned and actual radiotherapy doses. This study aimed to investigate the efficacy of robust and planning target volume (PTV) margin-based optimizations for the anatomical variations in helical tomotherapy for prostate cancer. PATIENTS AND METHODS: Ten patients underwent treatment-planning kilovolt computed tomography (kVCT) and daily megavolt computed tomography (MVCT). Two types of nominal plans, with a prescription of 60 Gy/20 fractions, were created using robust and PTV margin-based optimizations on kVCT for each patient. Subsequently, the daily estimated doses were recalculated using nominal plans, and all available MVCTs modified the daily patient-setup errors. Due to the difference in dose calculation accuracy between kVCT and MVCT, three scenarios with dose corrections of 1, 2, and 3% were considered in the recalculation process. The dosimetric metrics, including target coverage with the prescription dose, Paddick's conformity index, homogeneity index, and mean dose to the rectum, were analyzed. RESULTS: A dosimetric comparison of the nominal plans demonstrated that the robust plans had better dose conformity, lower target coverage, and dose homogeneity than the PTV plans. In the daily estimated doses of any dose-corrected scenario, the target coverage and dose sparing to the rectum in the robust plans were significantly higher than those in the PTV plans, whereas dose conformity and homogeneity were identical to those of the nominal case. CONCLUSION: Robust optimization is recommended as it accounts for anatomical variations during treatment regarding target coverage in helical tomotherapy plans for prostate cancer.

A case of renal abscess mimicking metastatic lesion in a patient with lung carcinosarcoma.

Renal abscesses require prompt diagnosis and appropriate intervention, as they can be life-threatening. However, diagnosis based solely on clinical findings is often challenging. We present the case of a 69-year-old woman with left renal masses on follow-up computed tomography (CT) after surgery for pT2aN0M0 lung carcinosarcoma. The masses were localized only in the left kidney without suspected metastatic lesions at other sites. The patient was referred to our department for further evaluation and treatment under a diagnosis of suspected metastatic lung carcinosarcoma of the left kidney. On enhanced CT, the left renal masses, the largest of which had a diameter of 40×36 mm had thick irregular walls gradually enhanced by the contrast media and an internal low-attenuation area. The masses showed heterogeneous signal intensity with a pseudocapsule on T2-weighted magnetic resonance imaging. Clinical symptoms such as fever or costovertebral angle tenderness were absent, and blood and urine tests were not sufficiently inflammatory to suggest a renal abscess. Histopathological findings on CT-guided renal biopsy revealed only inflammatory tissue and no tumor cells. However, because lung carcinosarcoma metastatic nodules could not be ruled out, laparoscopic left nephrectomy was performed for a definitive diagnosis and curative intent. The pathological diagnosis was renal abscess without malignant lesions. Here, we present a case of renal abscess mimicking metastatic lesions in a patient with lung carcinosarcoma. Accurately differentiating renal abscesses from metastatic renal tumors before treatment is often difficult. Renal abscess diagnosis should be considered through a comprehensive evaluation of the clinical findings of individual cases.

Long-term visual outcomes in pachychoroid spectrum diseases and its associating factors of eyes with chronic central serous chorioretinopathy.

To analyze the long-term visual outcomes of pachychoroid spectrum diseases (PSD). Retrospective study. We reviewed the medical charts of consecutive patients with PSD, including focal choroidal excavation (FCE), pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), and pachychoroid neovasculopathy (PNV). The patients initially visited the Tokyo University Hospital from January 2008 to March 2021. Survival analyses were performed, in which loss of vision was defined as visual acuity (VA) of 0.2 logarithm of minimal angle of resolution (logMAR) or worse, 0.5 logMAR or worse, or VA worsening by 0.3 logMAR or greater. Moreover, we further investigated factors associated with visual prognosis, particularly in the CSC group. A total of 741 eyes of 638 patients were included in this analysis. The CSC or PNV group showed significantly worse visual prognosis than the FCE&PPE group for VA to 0.2 logMAR or worse (P = 0.0117 or 0.0001, respectively) and for VA worsening by 0.3 logMAR or greater (P = 0.0283 or 0.0037, respectively). In the CSC group, unlike age, sex, or treatment history, the accumulative duration of subfoveal fluid existence ≥ 12 months (continuous or intermittent) was significantly associated with visual prognosis (P < 0.0001). Among PSD, CSC and PNV were associated with a higher risk of vision loss in the long term than FCE and PPE. The duration of subretinal fluid existence was identified as a significant factor affecting long-term visual outcomes in CSC.

Retinal sensitivity and fundus autofluorescence in adult-onset foveomacular vitelliform dystrophy.

The present study aimed to compare retinal sensitivity (RS) at each stage and to evaluate the relationship between RS and fundus autofluorescence (FAF) pattern in adult-onset foveomacular vitelliform dystrophy (AOFVD). We retrospectively reviewed 17 eyes of 13 patients with AOFVD. In addition to best-corrected visual acuity (VA), RS within the affected lesion and optical coherence tomography (OCT) measurements were carried out in each participant. All the examined eyes were classified into 4 stages and 3 FAF patterns. RS was superimposed on OCT fundus image and RS within the affected lesion was calculated in each eye. The relationships between visual functions (VA and RS within the affected lesion) and stages and also FAF patterns were analyzed using the linear mixed model. As a result, RS within the affected lesion was significantly associated with FAF pattern, but not with stage. In contrast, VA was correlated with neither stages nor FAF patterns. Our current result suggested that RS within the affected lesion was related to FAF patterns but this was not the case with VA in eyes with AOFVD, demonstrating the usefulness of measuring RS, not only VA, to comprehend the disease status in AOFVD.

Predictive factors for postoperative visual function in eyes with epiretinal membrane.

Our current study aimed to investigate the association of preoperative OCT parameters with visual function after vitrectomy surgery in eyes with epiretinal membrane (ERM). This study enrolled 33 eyes with ERM that underwent vitrectomy surgery. In addition to visual acuity (VA), metamorphopsia was measured pre- and postoperatively for each eye. Using the preoperative horizontal and vertical OCT images, SUKIMA (the gap area between the ERM and retinal surface) was measured respectively and the average of horizontal SUKIMA and vertical SUKIMA was used for the analysis. The associations of baseline parameters (age, axial length, preoperative central retinal thickness [CRT], inner nuclear layer [INL] thickness, ectopic inner foveal layer [EIFL] and SUKIMA) with postoperative VA, the change in VA, postoperative metamorphopsia and the improvement in metamorphopsia were investigated using multivariate regression analysis followed by the model selection. The result suggested that age and INL thickness were related to the postoperative VA, whereas age and preoperative CRT were significantly associated with the change in VA. In contrast, only SUKIMA was correlated with the postoperative metamorphopsia, whilst age, EIFL and SUKIMA were associated with the improvement in metamorphopsia. Measuring SUKIMA might be useful for predicting postoperative metamorphopsia and the improvement in metamorphopsia in ERM eyes.

Longitudinal anatomical and visual outcome of macular telangiectasia type 2 in Asian patients.

Limited information regarding the anatomical and visual prognosis of macular telangiectasia (MacTel) type 2 in the Asian population is currently available. Herein, we conducted a retrospective longitudinal analysis of Japanese patients diagnosed with MacTel type 2. Disease progression was evaluated using the Simple MacTel Classification developed by Chew EY et al. in 2023, and its association with visual changes was analyzed. Sixteen eyes of eight Japanese patients were included in the study, with an average follow-up period of 8.2 ± 3.9 years (range, 2.2-14.0). At the initial visit, 7 (44%) and 5 (31%) eyes were classified as Grade 2 (central ellipsoid zone break) and Grade 3 (noncentral pigment), respectively. The proportion of eyes that progressed by 1 or 2-steps in grade after 1, 3, 5, 8, and 12 years was 0%, 14%, 43%, 70%, and 100%, or 0%, 7%, 7%, 30%, and 75%, respectively. The visual acuity significantly deteriorated during the follow-up period, particularly in the two eyes with full-thickness macular holes (FTMH). Three out of 7 patients exhibited low serum serine concentrations, although no apparent correlation with anatomical or visual outcomes was observed. Overall, this cohort demonstrated chronic disease progression, both anatomically and functionally, in eyes with MacTel type 2, with FTMH potentially associated with greater visual loss.

Macular vessel density in central retinal artery occlusion with retinal arterial cannulation.

To characterize and compare macular vessel density in central retinal artery occlusion (CRAO) eyes with retinal arterial cannulation and CRAO eyes with standard treatment. This study was Cross-sectional, observational study. Twenty-two eyes with nonarteric CRAO which underwent retinal arterial cannulation and 19 eyes with nonarteric CRAO with standard treatment were included. Optical coherent tomography angiography (OCTA)-based macular vessel density and visual acuity were examined. The dynamic ranged-based normalized rates of vessel density was compared within each group at the first visit to the clinic and 7 days after the onset. Macular vessel density in cannulation group was significantly better at 7 days after the onset than that at the first visit (3.73 ± 3.02 mm-1 vs. 7.89 ± 1.02 mm-1, P = 0.0001), while there wasn't significant improvement of macular vessel density in standard treatment group at 7 days after the onset (2.13 ± 1.62 mm-1 vs. 2.89 ± 0.22 mm-1, P = 0.067). At one month after the onset, mean LogMAR visual acuity in CRAO eyes with cannulation significantly improved compared with that at the first visit after the onset (1.678 vs. 0.979, P = 0.00012). Macular vessel density loss in CRAO eyes was improved by retinal arterial cannulation. Early intervention of retinal arterial cannulation is useful for minimizing visual impairment in CRAO eyes.

Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3-Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3-Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial.

PURPOSE: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in breast cancer; high expression is associated with an adverse prognosis. Patritumab deruxtecan (HER3-DXd) is an investigational HER3-targeted antibody-drug conjugate that is being evaluated as a novel treatment in HER3-expressing advanced breast cancer in the U31402-A-J101 study. METHODS: Adults with disease progression on previous therapies were eligible. Patients in the dose-escalation, dose-finding, and dose-expansion parts received HER3-DXd 1.6-8.0 mg/kg intravenously once every 3 weeks or one of two alternative dosing regimens. In the dose-escalation part, the primary objectives were to determine the maximum tolerated dose and recommended dose for expansion (RDE). The safety and efficacy of the RDE were assessed during dose expansion. RESULTS: One hundred eighty-two enrolled patients received ≥1 dose of HER3-DXd. Patients had a median of five previous therapies for advanced disease. Efficacy results are reported across clinical subtypes: hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-negative) breast cancer (n = 113; objective response rate [ORR], 30.1%; median progression-free survival [mPFS], 7.4 months), triple-negative breast cancer (n = 53; ORR, 22.6%; mPFS, 5.5 months), and HER2-positive breast cancer (n = 14; ORR, 42.9%; mPFS, 11.0 months). Objective responses were observed in cancers with HER3-high and HER3-low membrane expression. Dose-limiting toxicities observed during dose selection were decreased platelet count and elevated aminotransferases. In dose expansion, GI and hematologic toxicities were the most common treatment-emergent adverse events (TEAEs) observed. Grade ≥3 TEAEs were observed in 71.4% of patients, and 9.9% discontinued treatment because of TEAEs. Three grade 3 and one grade 5 treatment-related interstitial lung disease events occurred. CONCLUSION: HER3-DXd demonstrated a manageable safety profile and durable efficacy in heavily pretreated patients across clinical subtypes. These data warrant further evaluation of HER3-DXd in patients with HER3-expressing metastatic breast cancer.

Investigating the clinical validity of the guided progression analysis definition with 10-2 visual field in retinitis pigmentosa.

PURPOSE: To investigate the clinical validity of the Guided Progression Analysis definition (GPAD) and cluster-based definition (CBD) with the Humphrey Field Analyzer (HFA) 10-2 test in retinitis pigmentosa (RP). METHODS: Ten non-progressive RP visual fields (VFs) (HFA 10-2 test) were simulated for each of 10 VFs of 111 eyes (10 simulations × 10 VF sequencies × 111 eyes = 111,000 VFs; Dataset 1). Using these simulated VFs, the specificity of GPAD for the detection of progression was determined. Using this dataset, similar analyses were conducted for the CBD, in which the HFA 10-2 test was divided into four quadrants. Subsequently, the Hybrid Definition was designed by combining the GPAD and CBD; various conditions of the GPAD and CBD were altered to approach a specificity of 95.0%. Subsequently, actual HFA 10-2 tests of 116 RP eyes (10 VFs each) were collected (Dataset 2), and true positive rate, true negative rate, false positive rate, and the time required to detect VF progression were evaluated and compared across the GPAD, CBD, and Hybrid Definition. RESULTS: Specificity values were 95.4% and 98.5% for GPAD and CBD, respectively. There were no significant differences in true positive rate, true negative rate, and false positive rate between the GPAD, CBD, and Hybrid Definition. The GPAD and Hybrid Definition detected progression significantly earlier than the CBD (at 4.5, 5.0, and 4.5 years, respectively). CONCLUSIONS: The GPAD and the optimized Hybrid Definition exhibited similar ability for the detection of progression, with the specificity reaching 95.4%.