MACULAR CHORIORETINAL ATROPHY AND VISUAL OUTCOMES IN RANIBIZUMAB- OR AFLIBERCEPT-TREATED MYOPIC CHOROIDAL NEOVASCULARIZATION.

PURPOSE: To investigate the predictors of macular chorioretinal atrophy, consisting of patchy atrophy (PA) at the macula and choroidal neovascularization (CNV)-related macular atrophy (CNV-MA), during treatment with ranibizumab or aflibercept for myopic CNV (mCNV) and its impact on visual outcomes. METHODS: This retrospective study included 82 eyes with treatment-naïve mCNV who were treated with pro re nata injections of ranibizumab or aflibercept. RESULTS: Nine eyes (11.0%) presented with macular PA at baseline (PA group), and 73 eyes (89.0%) did not (non-PA group). VA improved during the first year in the non-PA group; a similar trend was noted in the PA group until 3 months after initial treatment. This improvement was maintained until 24 months ( P < 0.001) in the non-PA group, but not in the PA group. In the PA group, macular chorioretinal atrophy progressed faster ( P < 0.0001), and CNV-MA was more frequent during the 2 years of treatments ( P = 0.04). Even non-PA group eyes sometimes developed CNV-MA (42% at Month 24) if they had a larger CNV and thinner subfoveal choroidal thickness at baseline, resulting in poorer visual prognosis ( P < 0.01). CONCLUSION: Macular PA at baseline was a risk factor for CNV-MA development and was associated with poor visual outcomes.

Three Cases of Arteritic Anterior Optic Neuropathy Several Months after COVID-19 Vaccination.

Background: Vaccines have been approved worldwide to control the coronavirus disease-19 (COVID-19). However, the postvaccination side effects remain controversial. Here, we describe three Japanese cases of arteritic anterior ischaemic optic neuropathy (AAION) following COVID-19 vaccination. Case presentation. The first case involved an 87-year-old woman who presented with vision loss in the right eye 2 months after her second COVID-19 vaccine and in the left eye 2 days later. The second case involved an 88-year-old woman who presented with vision loss in both eyes 3 months after receiving a second vaccine. The third case involved an 80-year-old man who presented with vision loss in the right eye 5 months after receiving a second vaccine. The C-reactive protein level and erythrocyte sedimentation rate were elevated in all patients. Biopsy of the temporal artery or auricular cartilage showed arteritic occlusion in case 2 and polychondritis in case 3. These patients were referred to a local Japanese hospital in 2021 over a period of no longer than 3 months. Conclusion: We observed three cases of AAION after the affected individuals received their second COVID-19 vaccine. Further long-term investigations of ophthalmological events after COVID-19 vaccination are warranted.

Photodynamic therapy combined with anti-vascular endothelial growth factor therapy for pachychoroid neovasculopathy.

This multicenter retrospective study was conducted to evaluate the 1-year treatment outcome of photodynamic therapy (PDT) combined with anti-vascular endothelial growth factor (VEGF) therapy for pachychoroid neovasculopathy (PNV). A total of 42 eyes of 42 patients with treatment-naïve PNV who were treated with PDT combined with intravitreal injections of an anti-VEGF agent (ranibizumab or aflibercept) for 1 year. All eyes showed exudative and/or hemorrhagic changes that affected the fovea at baseline. After the initial combination therapy, subfoveal choroidal thickness (SCT) and central retinal thickness (CRT) were significantly reduced and were maintained as such for 12 months (P < 0.01 in SCT and CRT). The best-corrected visual acuity (BCVA) (0.19 ± 0.30 at baseline) significantly improved at 3 months (0.15 ± 0.29, P < 0.05) and further improved at 12 months (0.10 ± 0.30, P < 0.01) when compared to that at baseline. After the initial combination therapy, 32 eyes (76.2%) required no additional treatments for 12 months. The mean number of additional PDT and intravitreal injections of anti-VEGF agents was 0.1 ± 0.3 and 0.9 ± 1.9, respectively. Of the 42 eyes included in this study, 22 eyes (52.4%) had polypoidal lesions at baseline. No significant differences in SCT, CRT, or BCVA were observed at any time points between eyes with and without polypoidal lesions. Of 20 eyes without polypoidal lesions, only 1 eye (5.0%) needed additional treatments. PNV, especially without polypoidal lesions, can be treated effectively with PDT combined with anti-VEGF therapy with few sessions.

Usefulness of Denoising Process to Depict Myopic Choroidal Neovascularisation Using a Single Optical Coherence Tomography Angiography Image.

Quality of single optical coherence tomography angiography (OCTA) images of myopic choroidal neovascularisation (mCNV) is poorer than in averaged images, although obtaining averaged images takes much time. This study evaluated the clinical usefulness of novel denoising process for depicting mCNV. This study included 20 eyes of 20 patients with mCNV. Ten en face images taken in a 3 × 3 mm macular cube were obtained from outer-retina-to-choriocapillaris layer. Three image types were prepared for analysis; single images before and after the denoising process accomplished deep learning (single and denoising groups, respectively) and up to 10 images were averaged (averaging group). Pairwise comparisons showed vessel density, vessel length density, and fractal dimension (FD) were higher; whereas, vessel density index (VDI) was lower in single group than in denoising and averaging groups. Detectable CNV indices, contrast-to-nose ratio, and CNV diagnostic scores were higher in denoising and averaging groups than in single group. No significant differences were detected in VDI, FD, or CNV diagnostic scores between denoising and averaging groups. The denoising process can utilise single OCTA images to provide results comparable to averaged OCTA images, which is clinically useful for shortening examination times with quality similar to averaging.

Efficacy of Photodynamic Therapy for Polypoidal Choroidal Vasculopathy Associated with and without Pachychoroid Phenotypes.

PURPOSE: To compare the efficacy of photodynamic therapy (PDT) in eyes with polypoidal choroidal vasculopathy (PCV) associated with and without pachychoroid phenotypes (pachychoroid PCV and nonpachychoroid PCV, respectively). DESIGN: Retrospective chart review. PARTICIPANTS: Patients previously diagnosed with PCV and initially treated with PDT. METHODS: Patients were classified as having pachychoroid- or nonpachychoroid-driven conditions. The long-term visual outcome and its associated factors were investigated. MAIN OUTCOME MEASURES: Visual acuity (VA) outcomes at 1, 2, 3, 4, and 5 years after initial PDT in pachychoroid and nonpachychoroid PCV. RESULTS: Of the 158 eyes, 88 (55.7%) met the criteria for pachychoroid PCV; 70 (44.3%) did not (nonpachychoroid PCV). In cases of pachychoroid PCV, VA improved significantly at 1 year (P = 0.042) and maintained baseline level at 5 years (P = 0.38). By contrast, VA continued to deteriorate in the nonpachychoroid PCV group during the follow-up period and had already declined significantly by the second year (P = 0.022, compared with baseline). Despite no difference in baseline VA between pachychoroid and nonpachychoroid PCV groups (P = 0.11), the VA at 5 years was significantly better in the pachychoroid PCV group compared with the nonpachychoroid PCV group (0.54±0.47 vs. 0.93±0.63, respectively; P = 0.23 × 10-3). The incidence of massive submacular hemorrhage (SMH) or vitreous hemorrhage (VH) was not different between groups at 5 years (P = 0.67), and their occurrence was associated with decreased VA in both the nonpachychoroid and pachychoroid PCV groups (coefficient ß, 0.361 and 0.481; P = 0.59 × 10-3 and P < 1.0 × 10-5, respectively). CONCLUSIONS: Five years after PDT treatment, VA was maintained at the baseline level in the pachychoroid PCV group but not in the nonpachychoroid PCV group. Massive SMH or VH during the follow-up period affected the final visual outcomes in both conditions.

Four-Year Outcome of Aflibercept for Neovascular Age-Related Macular Degeneration and polypoidal choroidal vasculopathy.

Intravitreal injections of anti-vascular endothelial growth factor agents such as ranibizumab and aflibercept are the first-line treatment for neovascular age-related macular degeneration (AMD). However, data about long-term outcome in real-world clinical practice is scarce. We recruited 98 AMD patients and investigated four-year visual outcome. During the four years, 25 patients dropped out. The survivors received 7.0 ± 0.1 injections during the first year and 8.0 ± 7.4 injections in the following three years. The logarithm of minimum angle of resolution (logMAR) at baseline, year one, and year four was 0.28, 0.14 (P = 0.033), and 0.22 (P = 0.697), respectively. The gain of vision was not different among AMD subtypes (typical AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation; P = 0.513) Among the investigated factors, the presence of external limiting membrane (ELM), the absence of vitreoretinal adhesion, and thicker choroid at baseline were associated with better logMAR values at year four (coefficient beta = -0.388, 0.201, and -0.001; P = 7.34 × 10-6; 0.01, and 0.028, respectively). In the present study, vision was retained at baseline level after the four-year treatment with aflibercept. The status of ELM, vitreoretinal adhesion, and choroidal thickness were predictive factors for final vision.

Association of handgrip strength with hospitalization, cardiovascular events, and mortality in Japanese patients with type 2 diabetes.

Handgrip strength is useful for the diagnosis of sarcopenia. We examined the associations of handgrip strength with all-cause mortality, cardiovascular events, and hospitalization in patients with type 2 diabetes. From April 2013 to December 2015, we conducted a retrospective cohort study to examine patients with type 2 diabetes whose handgrip strength was measured at our hospital. All patients were followed up until May 2016. A total of 1,282 patients (63.8 ± 13.9 years) were enrolled and followed up for 2.36 ± 0.73 years. During the follow-up period, 20 patients (1.6%) died, 14 (1.1%) experienced cardiovascular events, and 556 (43.4%) were admitted to our hospital for any diseases. Multiple regression analyses revealed that handgrip strength was favorably associated with abdominal obesity and renal function. Moreover, Cox proportional hazard analyses with adjustment for potential confounding variables revealed that handgrip strength was significantly associated with occurrence of CVD events and hospitalization in all subjects. In addition, handgrip strength was significantly associated with mortality and hospitalization in men and with hospitalization in women. Handgrip strength could be a prognostic indicator for health as well as a diagnostic marker of skeletal muscle mass loss in Japanese patients with type 2 diabetes.

Association of Vascular Versus Avascular Subretinal Hyperreflective Material With Aflibercept Response in Age-related Macular Degeneration.

PURPOSE: To investigate flow signal within subretinal hyperreflective material (SHRM) using optical coherence tomography angiography (OCTA) and its association with aflibercept treatment responses in treatment-naïve neovascular age-related macular degeneration (nAMD). DESIGN: Prospective consecutive interventional case series. METHODS: Forty-four eyes of 44 patients with treatment-naïve nAMD manifesting SHRM on OCT were studied. All patients underwent OCTA and received 3 monthly aflibercept injections. The intrinsic flow signals within SHRM were quantitatively analyzed using OCTA, and eyes were classified into the vascular and avascular SHRM groups. RESULTS: Of 44 eyes, 21 (47.7%) and 23 (52.3%) showed vascular SHRM and avascular SHRM, respectively. Compared with eyes with avascular SHRM, eyes with vascular SHRM showed higher rates of external limiting membrane (ELM) disruption owing to SHRM (P = .015), classic choroidal neovascularization (CNV) (85.7% vs 26.1%, P = .87 × 10-4), and intraretinal fluid (P = .008) at baseline. After 3 aflibercept injections, 38 eyes (86.4%) showed dry macula despite persistent SHRM in 24 eyes (54.5%). Compared with the eyes with resolved SHRM, those with persistent SHRM showed higher rate of vascular SHRM (75.0% vs 15.0%, P = .86 × 10-4), classic CNV (P = .032), absence of polypoidal lesion (P = .020), ELM disruption owing to SHRM (P = .042), and intraretinal fluid (P = .008). Dry macula after loading injections was significantly associated with SHRM resolution (P = .025). CONCLUSIONS: In nAMD, SHRM can be categorized as vascular and avascular by quantitative OCTA analysis. Vascular SHRM persisted after treatment and was associated with failure to achieve dry macula, suggesting that vascular SHRM is predictive of lower response to anti-VEGF therapy.

Serum Zn/Cu Ratio Is Associated with Renal Function, Glycemic Control, and Metabolic Parameters in Japanese Patients with and without Type 2 Diabetes: A Cross-sectional Study.

BACKGROUND: Zinc (Zn) and copper (Cu) may play a pivotal role in the pathogenesis of diabetes and diabetic complications by mediating oxidative stress. Both Zn deficiency and excess of Cu are associated with an increased risk of type 2 diabetes and cardiovascular disease. We aimed to investigate the relationships between serum Zn/Cu ratio and glycemic status, renal function, and metabolic parameters in patients with and without type 2 diabetes. METHODS: We conducted a cross-sectional study on 355 subjects (149 type 2 diabetic and 206 non-diabetic) in whom serum Zn and Cu levels were measured at the same time. Associations between serum Zn/Cu ratio and clinical data were evaluated using multiple regression analysis. We also evaluated associations between serum Zn/Cu ratio and the prevalence of type 2 diabetes and glycemic control by multivariate logistic regression analysis. RESULTS: Serum Zn/Cu ratio was positively associated with estimated glomerular filtration rate after adjustment for body mass index (BMI) (ß = 0.137, p = 0.014). Plasma B-type natriuretic peptide levels were negatively associated with serum Zn/Cu ratio after adjustment for age, sex, and BMI (ß = -0.258, p = 0.032). In patients with type 2 diabetes, serum Zn/Cu ratio was negatively associated with plasma HbA1c levels after adjustment for age, sex, and BMI (ß = -0.239, p = 0.003). In addition, multivariate logistic regression analysis revealed that the highest quartile of serum Zn/Cu ratio was associated with a reduced risk of poor (HbA1c ≥ 7%) glycemic control (odds ratio = 0.382; 95% confidence interval, 0.165-0.884; p = 0.025) in patients with type 2 diabetes. CONCLUSION: Serum Zn/Cu ratio was favorably associated with renal function in all subjects and glycemic control in patients with type 2 diabetes. The Zn/Cu ratio, in addition to the individual serum levels of trace elements, is important for metabolism in humans.

Association Between Insufficient Photoreceptor Layer Plugging and Postoperative Visual Outcome in the Surgically Closed Macular Hole.

PURPOSE: To investigate whether the photoreceptor layer status of the detached retina, which has the potential to plug the macular hole (MH), can predict postoperative visual acuity (VA). DESIGN: Retrospective, consecutive, observational case series. METHODS: A consecutive series of 48 eyes in 48 patients with surgically closed MHs were recruited into the study. Spectral-domain optical coherence tomography (SD OCT) images were obtained preoperatively and postoperatively. Length gaps between photoreceptor layers and the preoperative diameter of the basal MH in the detached part of the retina was calculated for the photoreceptor outer segment (OS) and the external limiting membrane (ELM). The postoperative photoreceptor layer status at the fovea, including continuity of the ELM line, inner segment ellipsoid line (ISe), and cone outer segment tip (COST) line, was categorized by graders. RESULTS: The preoperative OS gap length and ELM gap length correlated significantly with postoperative VA. A larger OS or ELM gap length was associated with a more severe postoperative photoreceptor layer status. Eyes with a moderately reflective lesion had a significantly longer OS gap length and ELM gap length, significantly worse postoperative VA, and more severe photoreceptor layer status than did eyes without such a moderately reflective lesion. Eyes with a better postoperative COST status had significantly better postoperative VA (P = .0465). CONCLUSIONS: OS and ELM gap length, which represent the degree of insufficiency of MH plugging, was strongly correlated with postoperative VA; moreover, these preoperative parameters were associated with the postoperative photoreceptor layer status, including glial cell proliferation.

Associations between lower extremity muscle mass and metabolic parameters related to obesity in Japanese obese patients with type 2 diabetes.

Background. Age-related loss of muscle mass (sarcopenia) increases the incidence of obesity in the elderly by reducing physical activity. This sarcopenic obesity may become self-perpetuating, increasing the risks for metabolic syndrome, disability, and mortality. We investigated the associations of two sarcopenic indices, the ratio of lower extremity muscle mass to body weight (L/W ratio) and the ratio of lower extremity muscle mass to upper extremity muscle mass (L/U ratio), with metabolic parameters related to obesity in patients with type 2 diabetes and obesity. Methods. Of 148 inpatients with type 2 diabetes treated between October 2013 and April 2014, we recruited 26 with obesity but no physical disability. Daily physical activity was measured by a triaxial accelerometer during a period of hospitalization, and which was also evaluated by our previously reported non-exercise activity thermogenesis questionnaire. We measured body composition by bioelectrical impedance and investigated the correlations of L/W and L/U ratios with body weight, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), visceral fat area, subcutaneous fat area, serum lipid profile, and daily physical activity. Results. The L/W ratio was significantly and negatively correlated with BMI, WC, WHR, body fat mass, body fat percentage, subcutaneous fat area, and serum free fatty acid concentration, was positively correlated with daily physical activity: the locomotive non-exercise activity thermogenesis score, but was not correlated with visceral fat area. The L/U ratio was significantly and positively correlated with serum high-density lipoprotein cholesterol. Conclusions. High L/W and L/U ratios, indicative of relatively preserved lower extremity muscle mass, were predictive of improved metabolic parameters related to obesity. Preserved muscle fitness in obesity, especially of the lower extremities, may prevent sarcopenic obesity and lower associated risks for metabolic syndrome and early mortality.

Associations of Low-Intensity Resistance Training with Body Composition and Lipid Profile in Obese Patients with Type 2 Diabetes.

Resistance training to increase muscle mass and functional capacity is an integral part of diet and exercise programs for the management of obesity and type 2 diabetes. Low-intensity resistance training with slow movement and tonic force generation (LST) may be a practical and safe regimen for elderly obese individuals but the health benefits are uncertain. This study investigated the effects of LST on body composition and metabolic parameters in obese patients with type 2 diabetes. Twenty-six obese patients with type 2 diabetes engaged in LST training during hospitalization and were advised to maintain this regimen for 12 weeks after discharge. We compared lipid profile, arterial stiffness, and body composition before and after LST training. After 12 weeks of LST training, the ratio of lower extremity muscle mass to body weight increased significantly (0.176 ± 0.028 to 0.184 ± 0.023, mean ± SD), while body fat mass and body fat percentage decreased significantly (36.2 ± 10.9 kg to 34.3 ± 9.4 kg and 41.2 ± 8.6% to 40.1 ± 7.7%, respectively). Moreover, high-density lipoprotein cholesterol was significantly increased (42.2 ± 14 mg/dl to 46.3 ± 12.4 mg/dl) and both free fatty acids and lipoprotein(a) were decreased (665.2 ± 212.1 µEq/l to 525.4 ± 231.3 µEq/l and 15.4 ± 18 mg/dl to 13.8 ± 18 mg/dl, respectively). No significant change was observed in arterial stiffness. Although this study was a non-controlled investigation and some confounding factors including dietary intake, medication and compliance with training might affect the study result, a brief (12-week) LST training program may be a safe and effective strategy for the management of obesity and type 2 diabetes.

Effects of aflibercept for ranibizumab-resistant neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: To evaluate visual and anatomic outcomes in response to the conversion of treatment in patients with neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) refractory to previous treatment. We also investigated the effect of genetic factors. METHODS: We recruited patients with AMD or PCV refractory to ranibizumab and initiated aflibercept treatment. Changes in the logarithm of minimum angle of resolution (logMAR) and central retinal thickness (CRT) measured using optical coherence tomography (OCT) 6 months after the conversion were compared between the AMD and PCV groups. We also genotyped each patient for the ARMS2 A69S, CFH Y402H, and I62V alleles, and investigated the association between genotype and treatment response. RESULTS: Mean age of the participants was 75.6 ± 8.0 years. There were 15 patients with AMD and 26 patients with PCV. While PCV patients gained about 1 line of vision (0.40 ± 0.37 to 0.31 ± 0.40, P = 0.003), AMD patients did not show significant improvement (0.41 ± 0.37 to 0.42 ± 0.39, P = 0.699) despite the decrease in CRT (202.1 ± 113.7 to 131.2 ± 55.7 µm, P = 0.003). The prevalence of dry retina after treatment was higher among PCV patients (80.8 vs 46.7 %, P = 0.024). There was no significant difference between patients with risk and non-risk alleles for ARMS2 A69S, CFH Y402H, and I62V. CONCLUSION: In AMD or PCV patients refractory to ranibizumab, switching to aflibercept is generally effective regardless of patient genotype. PCV patients may benefit more significantly than AMD patients.

Age-related effects of fasting on ketone body production during lipolysis in rats.

OBJECTIVE: The age-related effects of fasting on lipolysis, the production of ketone bodies, and plasma insulin levels were studied in male 3-, 8-, and 32-week-old Sprague-Dawley rats. METHODS: The rats were divided into fasting and control groups. The 3-, 8- and 32-week-old rats tolerated fasting for 2, 5, and 12 days, respectively. RESULTS: Fasting markedly reduced the weights of perirenal and periepididymal white adipose tissues in rats in the three age groups. The mean rates of reduction in both these adipose tissue weights during fasting periods were higher in the order of 3 > 8 > 32-week-old rats. Fasting transiently increased plasma free fatty acid (FFA), total ketone body, ß-hydroxybutyrate, and acetoacetate concentrations in the rats in the three age groups. However, plasma FFA, total ketone body, ß-hydroxybutyrate, and acetoacetate concentrations in the 3-week-old rats reached maximal peak within 2 days after the onset of fasting, although these concentrations in the 8- and 32-week-old rats took more than 2 days to reach the maximal peak. By contrast, the augmentation of plasma FFA, total ketone body, ß-hydroxybutyrate, and acetoacetate concentrations in the rats in the three age groups had declined at the end of each experimental period. Thus, the capacity for fat mobilization was associated with tolerance to fasting. Plasma insulin concentrations in the rats in the three age groups were dramatically reduced during fasting periods, although basal levels of insulin were higher in the order of 32 > 8 > 3 week-old rats. CONCLUSION: These results suggest that differences in fat metabolism patterns among rats in the three age groups during prolonged fasting were partly reflected the metabolic turnover rates, plasma insulin levels, and amounts of fat storage.

Dietary zinc-deficiency and its recovery responses in the thermogenesis of rats.

The aim of this study was to elucidate whether dietary zinc-deficiency and its recovery play a role in controlling autonomic thermoregulation. We investigated the effects of dietary zinc-deficiency and its recovery on autonomic thermoregulation by measuring the rectal temperature, an index of deep body temperature. The weaned male Sprague Dawley rats were randomly divided into the dietary zinc-deficient diet (0.6 mg zinc/kg diet) group and the control diet (35.2 mg zinc/kg diet) group, and were fed for 4 weeks. In the recovery period, the rats of two groups were fed with the control diet for 3 weeks. The rectal temperature was significantly decreased throughout the period of zinc-deficiency and the hypothermic responses during the experimental period were recovered to the control group levels at least within 1 week in the recovery process from dietary zinc-deficiency. These results suggest that the deep temperature in rats was clearly associated with the dietary zinc intake levels.

Different recovery responses from dietary zinc-deficiency in the distribution of rat granulocytes.

The purpose of this study was to elucidate the effects of the recovery from dietary zinc-deficiency on the number of total white blood cells (WBCs), neutrophils, eosinophils and basophils, and plasma zinc and corticosterone concentrations in weanling male Sprague Dawley rats. Rats (n=34) of the zinc-deficient diet (0.6 mg zinc/kg diet) and control diet (35.2 mg zinc/kg diet) groups were fed for 4 wk, and then rats of both groups were fed with the control diet for 3 wk. Zinc-deficiency increased duration-dependently and clearly the number of total WBCs, neutrophils and eosinophils, and the increased numbers of these cells recovered to the control levels in week 2 of the recovery. On the other hand, the number of basophils increased by the zinc-deficiency recovered to the control levels in week 1 of the recovery. Zinc-deficiency significantly decreased plasma zinc concentrations by 85%, and markedly increased plasma corticosterone concentrations by 317%, as compared with the control group. In the recovery period, plasma zinc and corticosterone concentrations recovered to the control levels in week 2 of the recovery. These results suggest that zinc-deficiency and its recovery responses in the number of granulocytes and total WBCs are reversible, and their recovery rates depend on the subsets of granulocytes in rats.