Incidence and prognosis of taxane-induced macular edema: a retrospective study from the Japan Clinical REtina Study Group (J-CREST).

Macular edema is a known side effect of taxane-based anticancer drugs. We retrospectively investigated data from 11 centers between January 2016 and December 2021. Among 14,260 patients, 30 (0.21%) developed macular edema; from these, the number of cases associated with nab-paclitaxel was 16 (0.43%), significantly higher than the number of cases associated with paclitaxel or docetaxel (P < 0.01). Visual acuity (VA) and retinal choroidal change were examined in 27 patients, with a follow-up of at least 3 months. The patients' mean age was 67.2 years; 14 (51.3%) were male and four (14.8%) had unilateral onset. The mean interval between anticancer drug initiation and the first ophthalmology visit was 290.1 days. Among the 20 patients who discontinued anticancer drugs, VA and edema significantly improved 2 months after discontinuation (LogMAR VA: 0.50 vs. 0.28, central retinal thickness: 472.7 µm vs. 282.5 µm, both P < 0.01). No significant changes were observed in the central choroidal thickness. A correlation was found between duration of taxane treatment and VA immediately before discontinuation of anticancer drugs (ß = 0.00050; 95% confidence interval: 0.00036-0.00097; P < 0.05). Although taxane-induced macular edema is reversible, slower anticancer drug discontinuation worsened VA, highlighting the need for regular ophthalmologic evaluation during treatments.

Multifunctionality of a low-specificity L-threonine aldolase from the hyperthermophile Thermotoga maritima.

The peptidoglycan of the hyperthermophile Thermotoga maritima contains an unusual D-lysine in addition to the typical D-alanine and D-glutamate. Previously, we identified the D-lysine and D-glutamate biosynthetic pathways of T. maritima. Additionally, we reported some multifunctional enzymes involved in amino acid metabolism. In the present study, we characterized the enzymatic properties of TM1744 (threonine aldolase) to probe both its potential multifunctionality and D-amino acid metabolizing activities. TM1744 displayed aldolase activity toward both L-allo-threonine and L-threonine, and exhibited higher activity toward L-threo-phenylserine. It did not function as an aldolase toward D-allo-threonine or D-threonine. Furthermore, TM1744 had racemase activity toward two amino acids, although its racemase activity was lower than its aldolase activity. TM1744 did not have other amino acid metabolizing activities. Therefore, TM1744 is a low-specificity L-threonine aldolase with limited racemase activity.

Recurrence Rate during 5-Year Period after Suspension of Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration.

Purpose: To determine the recurrence rate of neovascular age-related macular degeneration (nAMD) during a 5-year period after the suspension of anti-vascular endothelial growth factor (anti-VEGF) treatments. Methods: Thirty-four eyes of 34 nAMD patients who met the inclusion criteria and were treated by anti-VEGF drugs were studied. All met the treatment suspension criteria and were followed for 5 years after the suspension of the anti-VEGF treatment. Patients with a recurrence within one year were placed in Group A, and patients with a recurrence between 1 and 5 years were placed in Group B. The rate and time of a recurrence were analyzed using the Kaplan-Meier method. We also examined whether there were differences in the baseline factors of age, sex, subtype, treatment period, and treatment interval between Groups A and B. Results: Twenty-five of 34 eyes (73.5%) had a recurrence within 5 years of stopping the anti-VEGF treatments. Thirteen (52.0%) of the 25 eyes had a recurrence within 1 year, 4 (16.0%) eyes between 1 and 2 years, 4 (16.0%) eyes between 2 and 3 years, 2 (8%) between 3 and 4 years, and 2 eyes (8%) between 4 and 5 years. The baseline factors were not significantly different between Groups A and B. Conclusions: The results showed that the recurrence rate was highest within one year after the suspension of the anti-VEGF treatments, with a number of recurrences one year after the suspension. Clinicians should remember that nAMD may recur several years after the suspension of anti-VEGF treatments.

Efficacy and Safety of TAS-303 in Female Patients With Stress Urinary Incontinence: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: We aimed to evaluate the therapeutic efficacy and safety of TAS-303, a highly selective noradrenaline reuptake inhibitor, in Japanese women with stress urinary incontinence (SUI). MATERIALS AND METHODS: A double-blind, placebo-controlled, phase 2 study randomized women with SUI symptoms to once-daily oral administration of TAS-303 18 mg or placebo for 12 weeks. The primary endpoint was percent change from baseline to Week 12 in mean SUI episode frequency per 24 hours (SUIEF) in the per-protocol set. The secondary endpoints were the proportion of patients with ≥ 50% reduction in mean SUIEF, incontinence episode frequency, incontinence amount, health-related quality of life, and safety in the full analysis set. RESULTS: In total, 231 patients were randomized to TAS-303 (n = 116) or placebo (n = 115). At Week 12, TAS-303 had superior efficacy to placebo, with a least squares mean percent change in mean SUIEF of -57.7% vs -46.9%, respectively, in the per-protocol set (least squares mean difference -10.8%; P = .036). TAS-303 showed some evidence of improved incontinence episode frequency, incontinence amount, and health-related quality of life (although not statistically significant) at Week 12 vs placebo in the full analysis set. The between-group difference in SUIEF improvement was more clearly confirmed in patients with ≥ 2 SUI episodes daily at baseline. All adverse events (AEs) with TAS-303 were mild or moderate; there were no serious AEs, AEs leading to discontinuation, or nervous system- or gastrointestinal-related (eg, nausea or vomiting) adverse drug reactions. CONCLUSIONS: Once-daily TAS-303 18 mg showed superior efficacy to placebo for the treatment of SUI in Japanese women, with an adequate safety profile. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04512053; Japan Registry of Clinical Trials: jRCT2080225307 (JapicCTI-205403 before site integration).

Function and Circulation of the Retina and Choroid in Case of Indolent Nonprogressive Multifocal Choroidal Lesions.

Indolent nonprogressive multifocal choroidal lesions have been reported to be benign choroidal lymphatic lesions that do not affect the visual function. However, as best known, there are no reports on whether these lesions affect the circulation and function of the retina and choroid. We report a case of indolent nonprogressive multifocal choroidal lesions in which retinal images were available to assess the retinal and choroidal circulation and whether it impacted the retinal function. The patient was a 45-year-old man. Swept-source optical coherence tomography (OCT) showed multiple well-defined, uniform, hyporeflective cavernous lesions in the choroidal layer. Then a diagnosis of indolent nonprogressive multifocal choroidal lesions was made based on the similarity of the features with those reported. OCT angiography showed no blood flow signals in the lesions and reduced blood flow signals in the choroid and choriocapillaris directly above the lesions. Fundus autofluorescence showed retinal pigment epithelial damages that were colocalized with the choroidal lesions. We then performed static visual field testing and multifocal electroretinography (mfERG). The static visual field test showed no decrease in sensitivity in the entire visual field, and mfERG showed no decrease in the amplitudes or implicit times indicating normal retinal function. In indolent nonprogressive multifocal choroidal lesions, the photoreceptor function is preserved but a mild retinal pigment epithelium disorder is present. Thus, the follow-up examinations of indolent nonprogressive multifocal choroidal lesions should include retinal function tests.

Effects of angle of incidence of stimulus light on photopic electroretinograms of zebrafish larvae.

In electroretinographic (ERG) recordings of zebrafish, the light stimulus is usually delivered by a fiber optic cable. The purpose of this study was to determine whether the angle of incidence of the stimulus light from the fiber optic cable will affect the amplitudes and implicit times of the ERGs of zebrafish larvae. The larvae were positioned on their side with the right eye pointed upward. The light stimuli were delivered by a fiber optic cable from three directions of the larvae: frontal 0° (F0°), dorsal 30°(D30°), and ventral 30°(V30°). Photopic ERGs were recorded from 16 larvae at age 5-6 days post-fertilization. Our results showed that the mean amplitude of the b-wave elicited at D30° and V30° stimulation was significantly smaller than that elicited at F0° stimulation (P = 0.014 and P = 0.019, respectively). In addition, the mean amplitude of the d-wave elicited at D30° and V30° stimulation was significantly smaller than that elicited at F0° stimulation (P < 0.0001 and P = 0.015, respectively). However, the difference between the b-wave amplitudes elicited at D30° and V30° stimuli were not significant (P = 0.98), and the d-wave amplitudes were also not significantly different (P = 0.20). The average b-wave amplitudes elicited at D30° stimulation was 84.6 ± 15.7% and V30° stimulation was 84.8 ± 17.4% relative to that of F0° stimulation. The average d-wave amplitudes elicited by D30° stimulation was 85.5 ± 15.2% and by V30° stimulation was 79.0 ± 11.0% relative to that of F0° stimulation. The differences in the implicit times of the b- and d-wave elicited by the different directions of stimulation were not significant (P = 0.52 and P = 0.14, respectively). We conclude that the amplitude of the photopic ERGs is affected by the angle of the incident light. Thus, it would be better to use ganzfeld stimuli to elicit maximum b- and d-wave amplitudes of the photopic ERGs of zebrafish larvae.

Choroidal Osteoma With Choroidal Excavation Due to Decalcification Five Years After Photodynamic Therapy: A Case Report.

A choroidal osteoma (CO) is a relatively rare, benign tumor with ossification that develops in the choroid and undergoes enlargement and decalcification in its natural course. Photodynamic therapy (PDT) is used to induce decalcification, but there are few reports on individual cases treated with PDT. A 47-year-old Japanese man who had reduced decimal visual acuity (VA) of the right eye to 0.7 due to a CO away from the fovea was treated with PDT. The PDT resulted in a partial decalcification of CO, and the visual acuity improved to 1.0. However, the tumor slowly expanded, eventually reaching the central fovea. Decalcification and focal choroidal excavation occurred during this natural course of the disease. Although his metamorphopsia worsened, his VA was maintained at 1.0. This case highlights that a CO partially decalcified after PDT can still enlarge and decalcify over several years. These findings indicate the need for careful and continuous monitoring of eyes with a CO.

Case of acute retinal necrosis with rapid progression to proliferative vitreoretinopathy: A case report.

RATIONALE: Acute retinal necrosis (ARN) was first reported in 1971 by Urayama et al as an acute uveitis accompanied by retinal arteritis and white retinal lesions in the peripheral retina that can progress to a rhegmatogenous retinal detachment (RRD). We have experienced a case of ARN that, unlike the common developmental course to an RRD associated with ARN, progressed to proliferative vitreoretinopathy (PVR) involving the entire retina in 2 days. The purpose of this report is to present our findings in the case of ARN with an atypical rapid time course. PATIENT CONCERNS: The patient was a 56-year-old woman who was treated for uveitis of unknown origin by her primary care physician. She was referred to our hospital because of a worsening of the fundus findings. DIAGNOSIS: Fundus examination in our hospital revealed vitreous opacities in the right eye, yellowish-white lesions extending around the retina, and some retinal hemorrhages. Because the retinal changes suggested ARN, we performed a polymerase chain reaction of the anterior atrial fluid and detected varicella-zoster virus. Then, the diagnosis of ARN was confirmed, and treatment was begun. At 1 month and a half after beginning the treatment, focal retinal traction was observed in the right fundus. Two days later, a circumferential PVR and a total retinal detachment were detected. INTERVENTIONS: We then performed vitrectomy with an encircling buckle and a silicone oil tamponade. OUTCOMES: Our examination 6 months postoperatively showed that the retina was attached and the BCVA was 20/200. LESSONS: Our findings of a case of ARN showed that the progression from a local vitreous traction to a full circumferential PVR can develop in 2 days.

Rapid Onset of De Novo Rectal Prolapse Following Colpocleisis.

INTRODUCTION: The aim of this video case series is to demonstrate our experience of the clinical findings and the surgical management of the rapid onset de novo rectal prolapse (RP) following colpocleisis METHODS: This is a case series of three patients who developed de novo RP within 1 month after colpocleisis, which was repaired by laparoscopic ventral mesh rectopexy (LVMR). The video shows the physical, radiological, and intraoperative findings of these patients. A retrospective review of our surgical cases of RP was also performed to analyze the onset timing of de novo RP after various pelvic organ prolapse (POP) procedures. RESULTS: The pathological condition of all three patients' RP was evacuation enterocele, and LVMR was feasible without postoperative complications or recurrences. In the retrospective case review of 158 RP surgeries in our institution (June 2015 to September 2023), 18 cases (11.4%) occurred following POP surgery. De novo RP following colpocleisis developed significantly earlier than those following other procedures (average: 6.1 vs 66.4 months, p = 0.010). CONCLUSIONS: Although de novo RP following colpocleisis is relatively rare, this complication could have a detrimental effect on patients' quality of life. Preoperative informed consent may be advisable before planning colpocleisis.

A 31-year follow-up of those with occult spinal dysraphism, who underwent spinal cord untethering: Lower urinary tract function, skin stigmata, fertility, and work participation.

OBJECTIVES: This study evaluated patients with occult spinal dysraphism who underwent spinal cord untethering. METHODS: Twenty-four patients who visited us between 1983 and 2000 were followed-up for a mean duration of 31 years. We studied their lower urinary tract function, skin stigmata, fertility, and work participation. RESULTS: Questionnaires sent in 2022 revealed that 5 patients had normal voiding (Group A) and 19 patients had abnormal voiding (Group B). Groups A and B underwent spinal cord untethering at a mean age of 5.7 and 13.0 years, respectively, showing a significant statistical difference (p = 0.036). After spinal cord untethering, the number of patients with detrusor normoactivity increased from 0 to 5, i.e., 3 of 6 with detrusor overactivity (50%), 1 of 2 not examined, and 1 of 5 not known. Patients with detrusor underactivity also increased from 11 to 19. Severity of incontinence in the International Consultation on Incontinence Questionnaire-Short Form resulted in a mean value of 2.4 in Group A, which was significantly superior to the mean value of 9.1 in Group B (p = 0.004). Fourteen patients (58.3%) were married and had 21 healthy children. A majority of patients have had full-time jobs. A variety of skin stigmata were present in the lumbosacral region, and changes in vesico-urethral configurations were observed during a video-urodynamic study. CONCLUSIONS: Our study identified that the early timing of spinal cord untethering performed in neonates or infants and detrusor overactivity prior to untethering surgery are important factors in achieving normal bladder function.

Development of acute hydrops in eye with infectious keratitis: A case report.

Purpose: To determine the characteristics of an eye that developed acute hydrops while being treated for infectious keratitis. Observation: A 35-year-old man presented with pain and blurred vision in his left eye. He had undergone cataract surgery seven years earlier and was being treated for poorly controlled atopic dermatitis. The decimal best-corrected visual acuity (BCVA) of the left eye was 0.01. Slit-lamp microscopy showed conjunctival injection, corneal opacification, and a corneal ulcer. The patient was diagnosed with infectious keratitis and was treated with topical and systemic antibiotics. During the hospitalization, the patient was noted to rub his eyes frequently and vigorously. Five days after the first visit, the cornea protruded markedly, and the stroma surrounding the ulcerated area was edematous. These findings led to a diagnosis of acute hydrops.Penetrating keratoplasty was performed to prevent corneal perforation. Histopathological study of the excised cornea showed stromal edema, infiltration of leukocytes, and a tear in Descemet's membrane. Unfortunately, the patient developed endophthalmitis the day after the surgery. The anterior chamber was irrigated with antibiotics, and antibiotics were also injected into the vitreous. The endophthalmitis gradually subsided, and two years after the surgery, the patient's decimal BCVA had improved to 0.6. Conclusion and importance: Vigorous eye rubbing in cases of infectious keratitis can induce acute hydrops, and timely surgical intervention is recommended.

Characterization of the visually impaired patients with diabetes mellitus in Japan.

AIMS/INTRODUCTION: To conduct a multicenter survey of visually impaired patients with diabetes mellitus (DM) and to identify the physical and ocular characteristics that lead to blindness in Japan. MATERIALS AND METHODS: Visually impaired patients with diabetes mellitus in Japan were divided into blind and low-vision groups according to the World Health Organization classification. Data on parameters related to diabetes mellitus and ocular complications in the right and left eyes were collected from 19 highly advanced medical facilities and compared between the two groups. RESULTS: Among 408 visually impaired persons (blind group: 257, low-vision group: 151), 72.1% were under 70 years of age. The rates of neovascular glaucoma (NVG) (right eye, P = 0.041; left eye, P = 0.0031) or proliferative diabetic retinopathy (PDR) (right eye: P = 0.014, left eye: P = 0.0047) and the rate of proliferative membrane beyond half of the retinal area (right eye: P = 0.0263, left eye: P = 0.037) were significantly higher in the blind group. The direct cause of visual impairment was retinal atrophy, common in both groups. Neovascular glaucoma and diabetic macular edema were equally prevalent in the blind and low-vision groups, respectively. CONCLUSIONS: In Japan, blind patients with diabetes mellitus are characterized by severe conditions such as neovascular glaucoma and progressive proliferative diabetic retinopathy upon their initial visit to an advanced care facility. These results highlight the importance of monitoring retinopathy through regular ophthalmological examinations, internal medicine, and appropriate therapeutic intervention.

Effects of Bifidobacterium longum BB536 and Bifidobacterium breve MCC1274 on Body Composition in Normal and Overweight Adults in Randomized Placebo-Controlled Study.

Visceral fat accumulation is considered to be associated with a higher risk of chronic diseases. We investigated the effects of Bifidobacterium longum subsp. longum (B. longum) BB536 and Bifidobacterium breve (B. breve) MCC1274 on body composition, including visceral fat, in a randomized, parallel-group, placebo-controlled study. Participants were between 29 and 64 years of age and had a body mass index (BMI) of greater than 23 and less than 30. One hundred participants were randomly assigned to the probiotics group or placebo group. Participants were administered probiotic capsules containing 1 × 1010 colony-forming units (CFUs) of B. longum BB536 and 5 × 109 CFU of B. breve MCC1274 or placebo capsules without bifidobacteria for 16 weeks. In the probiotics group, abdominal visceral fat area, total abdominal fat area, and serum triglyceride levels were significantly decreased compared to those in the placebo group. Additionally, the increase in BMI observed in the placebo group was significantly suppressed in the probiotics group. This study showed that B. longum BB536 and B. breve MCC1274 reduced abdominal visceral fat and total fat levels in healthy normal and overweight adults, suggesting their beneficial effects on body composition.

Quantitative lipid composition characterization of intact liposomes via 31P nuclear magnetic resonance spectroscopy.

Drug delivery systems (DDS) are important methods to maximize drug efficacy by enabling in vivo accumulation at the target site. Liposomes, which are nanoscale vesicles consisting of lipid bilayers, are widely used for clinical DDS. The lipid composition of an intact liposome is a significant factor that directly affects its characteristics and functions. Thus, it is important to develop quantitative or qualitative analytical methods to characterize the lipid composition. Nuclear magnetic resonance (NMR) of phosphorus (31P) is a particularly sensitive and non-destructive approach because phospholipid components have one 31P nucleus per molecule. Here, we demonstrate quantitative observations of individual phospholipids in intact liposomes via solution 31P-NMR. In addition, the 31P linewidths became narrower if the liposomes contained > 10 mol% of polyethylene glycol-(PEGylated) phospholipids, which also contributed to liposome down-sizing. Down-sizing and PEGylation are important strategies for efficient drug delivery. Hence, 31P-NMR can be used to analyze phospholipids in liposomes and related pharmaceutical preparations for quality control.

Effect of Lipid Composition on the Interaction of Liposomes with THP-1-Derived Macrophages.

Recently, liposomal formulations that target macrophages have been used to treat lung diseases. However, the detailed mechanism of the cellular uptake must be elucidated to identify a formulation with excellent cellular uptake efficiency to treat non-tuberculous mycobacterial lung disease. We studied the effect of lipid composition on the cellular uptake of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/cholesterol (Chol) liposomes with a size of approximately 200 nm into THP-1-derived macrophages. The amount of DPPC/Chol liposomes (80/20 mol%) was greater than that of DPPC/Chol (60/40 mol%) and DPPC/Chol (67/33 mol%) liposomes. The anisotropy of 1,6-diphenyl-1,3,5-hexatriene indicated that the membrane fluidity of the DPPC/Chol (80/20 mol%) liposomes was higher than that of the other two liposomes. DPPC/Chol (80/20 mol%) and DPPC/Chol (67/33 mol%) liposomes were taken up via clathrin- and caveolae-mediated endocytosis and phagocytosis. However, proteins involved in cellular uptake through ligand-receptor interactions were adsorbed to a greater extent on DPPC/Chol (80/20 mol%) liposomes than on DPPC/Chol (67/33 mol%) liposomes. Pretreatment of cells with antibodies against the low-density lipoprotein receptor and scavenger receptor type B1 largely inhibited the uptake efficiency of DPPC/Chol (80/20 mol%) liposomes. Our results indicate that the membrane fluidity of DPPC/Chol liposomes, which is controlled by the Chol ratio, is an important factor in controlling protein adsorption and the subsequent uptake efficiency of liposomes.

Reliability of Binocular Esterman Visual Field Test in Patients with Glaucoma and Other Ocular Conditions.

The binocular Esterman visual field test (EVFT) of 120 points was the first method to quantify the defects in the binocular visual field. It is used in many parts of the world as a standard test to determine whether an individual has the visual capabilities to drive safely. In Japan, it is required for the grading and issuance of visual disability certificates. The purpose of this study was to determine the reliability of the EVFT results. We studied 104 patients who had undergone the binocular EVFT at Mie University Hospital. Their mean age was 68.0 ± 11.4 years, and the best-corrected visual acuity of the better eye was 0.18 ± 0.38 logMAR units. The EVFT was performed twice on the same day, and the results of the first and second tests were compared. The mean Esterman scores for the first and second test were 89.3 ± 30.5 and 89.1 ± 30.2, respectively, and the test times were 338.9 ± 86.8 and 336.7 ± 76.4 s, respectively. The differences were not significant (p = 0.69 and p = 0.33). In the Bland-Altman analyses (second-first test) of the Esterman scores, the mean difference was 0.38 without significant fixed errors (p = 0.20) or proportional errors (p = 0.27). The limits of agreement within the 1.96 standard deviation were -8.96 to +9.45 points. The agreement rate for the most peripheral 24 test points was significantly lower than the agreement rate for the other 96 test points (p < 0.01). The agreement rate of the upper visual field was significantly lower than that of the lower field (p < 0.01). The overall reliability rate of the EVFT is acceptable, but the peripheral and upper test points have relatively low reliability rates. These findings are important for interpretations of the EVFT results.

Effects of Heat-Killed Lacticaseibacillus paracasei MCC1849 on Immune Parameters in Healthy Adults-A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.

Previous clinical studies have shown that heat-killed Lacticaseibacillus paracasei MCC1849 suppresses subjective symptoms among healthy adults. However, the mechanism underlying this beneficial effect remains unclear. This clinical study aimed to investigate the effects of MCC1849 on immune functions in humans. In this randomized, double-blind, placebo-controlled, parallel-group study, 100 healthy adults were randomly divided into MCC1849 or placebo groups. Participants ingested test powder with 5 × 1010 MCC1849 cells or placebo powder for 4 weeks. Immune functions were evaluated using expression levels of CD86 and HLA-DR on dendritic cells (DCs), neutrophils, and natural killer cells. The expression levels of interferon (IFN)-α, -ß, and -γ in peripheral blood mononuclear cells incubated with Cpg2216 in vitro were quantified. Efficacy analysis was performed on participants in the per-protocol set (placebo group; n = 47, MCC1849 group; n = 49). The expression level of CD86 on pDCs and the gene expression levels of IFN-α, -ß, and -γ upon TLR9 agonist stimulation were significantly higher in the MCC1849 group at 4 weeks. No side effects were observed. This is the first report to show the positive effects of MCC1849 on human immune cells. These findings reveal one possible mechanism of how MCC1849 suppresses subjective symptoms.

Case of persistent corneal epithelial damage after cataract surgery leading to diagnosis of vitamin A deficiency.

PURPOSE: To report our findings of reduced full-field electroretinograms (ff-ERGs) and abnormal optical coherence tomographic (OCT) images in a patient with poor visual acuity after cataract surgery who was eventually diagnosed with vitamin A deficiency (VAD). METHODS: This was a clinical study of a patient who complained of blurred vision after cataract surgery. To determine the cause of the reduced vision, we recorded full-field electroretinograms (ff-ERGs) to determine the scotopic and photopic status of the retina. We also performed optical coherence tomography to assess the changes in the retinal structure. Serological tests were performed. RESULTS: A 74-year-old man presented with persistent corneal epithelial damages and reduced vision that developed after conventional cataract surgery. OCT showed an interrupted ellipsoid zone, and fundus autofluorescence (FAF) showed a severe hypofluorescence in the retina of the left eye. The scotopic ff-ERGs were severely reduced, and the photopic ff-ERGs were mildly reduced. Serological examinations revealed a vitamin A concentration < 7 IU/dL (normal, 97-316 IU/dL). Based on these findings, we diagnosed the patient with VAD and started treatment with oral vitamin A supplements. After three months, his visual acuity, ff-ERGs, and OCT findings recovered to normal levels. The amplitudes and implicit times of the RETeval flicker ERGs increased to be within the normal range, and the hypofluorescence of the left eye disappeared. The length of the photoreceptor outer segments increased after the vitamin A supplementation. CONCLUSION: Our findings indicate that the ERGs are helpful for diagnosing patients with VAD associated with persistent corneal epithelial damages.

Novel tetrahydrofolate-dependent d-serine dehydratase activity of serine hydroxymethyltransferases.

d-Serine plays vital physiological roles in the functional regulation of the mammalian brain, where it is produced from l-serine by serine racemase and degraded by d-amino acid oxidase. In the present study, we identified a new d-serine metabolizing activity of serine hydroxymethyltransferase (SHMT) in bacteria as well as mammals. SHMT is known to catalyze the conversion of l-serine and tetrahydrofolate (THF) to glycine and 5,10-methylenetetrahydrofolate, respectively. In addition, we found that human and Escherichia coli SHMTs have d-serine dehydratase activity, which degrades d-serine to pyruvate and ammonia. We characterized this enzymatic activity along with canonical SHMT activity. Intriguingly, SHMT required THF to catalyze d-serine dehydration and did not exhibit dehydratase activity toward l-serine. Furthermore, SHMT did not use d-serine as a substrate in the canonical hydroxymethyltransferase reaction. The d-serine dehydratase activities of two isozymes of human SHMT were inhibited in the presence of a high concentration of THF, whereas that of E. coli SHMT was increased. The pH and temperature profiles of d-serine dehydratase and serine hydroxymethyltransferase activities of these three SHMTs were partially distinct. The catalytic efficiency (kcat /Km ) of dehydratase activity was lower than that of hydroxymethyltransferase activity. Nevertheless, the d-serine dehydratase activity of SHMT was physiologically important because d-serine inhibited the growth of an SHMT deletion mutant of E. coli, ∆glyA, more than that of the wild-type strain. Collectively, these results suggest that SHMT is involved not only in l- but also in d-serine metabolism through the degradation of d-serine.