[The application and usefulness of virtual reality aimed at encouraging an understanding of and reducing and eliminating prejudice towards dementia patients among local residents].

AIM: To demonstrate the usefulness of a virtual reality device that authentically portrays the emotions of dementia patients and their families (VR Dementia Experience) for encouraging an understanding of and reducing and eliminating prejudice towards dementia patients among local residents. METHOD: In Prefecture T, Town N, 85 residents of Neighborhood A were chosen as the intervention group, and 95 residents of Neighborhood B were chosen as the non-intervention group. The VR Dementia Experience was provided only to the residents of Neighborhood A. Residents of both neighborhoods completed a 35-item questionnaire regarding their degree of understanding and prejudice towards dementia patients before and after the intervention. RESULTS: Seventy-seven residents of Neighborhood A and 82 residents of Neighborhood B were analyzed. Their gender, age, and pre-intervention test baseline values were equivalent in the degree of understanding and prejudice. Significant increases were observed in 9 of 35 items for Neighborhood A residents (7 understanding-related, 2 prejudice-related) and 2 items for Neighborhood B residents (1 understanding-related, 1 prejudice-related). To ascertain the usefulness of the VR Dementia Experience, we compared the number of items with a significant increase: 9/35 (25.7%) in Neighborhood A and 2/35 (5.7%) in Neighborhood B. An effect (≥ 20%) was observed among the residents of Neighborhood A. Furthermore, after exposure to the VR Dementia Experience, the connection between understanding, prejudice, and dementia was strengthened among the residents of Neighborhood A compared to the residents of Neighborhood B. CONCLUSION: The VR Dementia Experience is a useful tool for encouraging an understanding of and reducing and eliminating prejudice towards dementia patients among local residents. However, to encourage the widespread usage of the technology, we should compare results with other public awareness campaigns as well as make improvements to the device and its VR content.

Topical betamethasone butyrate propionate exacerbates pressure ulcers after cutaneous ischemia-reperfusion injury.

Ischaemia-reperfusion (I/R) is involved in the development of various organ diseases. There has been increasing evidence that cutaneous I/R injury is associated with the pathogenesis of pressure ulcers (PUs), especially at the early stage presenting as non-blanchable erythema. However, there is no evidence-based treatment for early-stage PUs. Our objective was to assess the effects of topical steroid on the development of PUs after cutaneous I/R injury in mice. Cutaneous I/R was performed by trapping the dorsal skin between two magnetic plates for 12 h, followed by plate removal. Topical application of betamethasone butyrate propionate (BBP) in I/R areas significantly increased the size of PUs after I/R. The number of thromboses was increased, and CD31(+) vessels were decreased in the I/R area treated with topical BBP. The number of oxidative stress-associated DNA-damaged cells and apoptotic cells in the I/R area was increased by topical BBP treatment. In addition, the mRNA level of NADPH oxidase 4 (Nox4), the essential enzyme that produces reactive oxygen species, was significantly increased and that of NF-E2-related factor 2 (Nrf2), a transcription factor that regulates the expression of antioxidant proteins, was inhibited in the I/R area treated by BBP. The number of CD68(+) macrophages and the level of transforming growth factor-beta in lesional skin were also decreased by BBP. These results suggest that a topical steroid might accelerate the formation of PUs induced by cutaneous I/R injury by aggravating oxidative stress-induced tissue damage. Topical steroids might not be recommended for the treatment of acute-phase decubitus ulcers.

Increased susceptibility to oxidative stress- and ultraviolet A-induced apoptosis in fibroblasts in atypical progeroid syndrome/atypical Werner syndrome with LMNA mutation.

Atypical progeroid syndrome (APS), including atypical Werner syndrome (AWS), is a disorder of premature ageing caused by mutation of the lamin A gene, the same causal gene involved in Hutchinson-Gilford syndrome (HGS). We previously reported the first Japanese case of APS/AWS with a LMNA mutation (p.D300N). Recently, it has been reported that UVA induced abnormal truncated form of lamin A, called progerin, as well as HGS-like abnormal nuclear structures in normal human fibroblasts, being more frequent in the elderly, suggesting that lamin A may be involved in the regulation of photoageing. The objective of this study was to elucidate the sensitivity to cell damage induced by oxidative stress or UVA in fibroblasts from APS/AWS patient. Using immunofluorescence staining and flow cytometry analysis, the amount of early apoptotic cells and degree of intra-cellular reactive oxygen species (ROS) generation were higher in H2 02 - or UVA-treated APS/AWS fibroblasts than in normal fibroblasts, suggesting that repeated UV exposure may induce premature ageing of the skin in APS/AWS patients and that protecting against sunlight is possibly important for delaying the emergence of APS/AWS symptoms. In addition, we demonstrated that H2 O2 -, or UVA-induced apoptosis and necrosis in normal and APS/AWS fibroblasts were enhanced by farnesyltransferase inhibitor (FTI) treatment, indicating that FTI might not be useful for treating our APS/AWS patient.

Genome-wide variation in the pinewood nematode Bursaphelenchus xylophilus and its relationship with pathogenic traits.

BACKGROUND: Bursaphelenchus xylophilus is an emerging pathogenic nematode that is responsible for a devastating epidemic of pine wilt disease across Asia and Europe. In this study, we report the first genome-wide variation analysis of the nematode with an aim to obtain a full picture of its diversity. METHODS: We sequenced six key B. xylophilus strains using Illumina HiSeq sequencer. All the strains were isolated in Japan and have been widely used in previous studies. Detection of genomic variations were done by mapping the reads to the reference genome. RESULTS: Over 3 Mb of genetic variations, accounting for 4.1 % of the total genome, were detected as single nucleotide polymorphisms or small indels, suggesting multiple introductions of this invaded species from its native area into the country. The high level of genetic diversity of the pine wood nematode was related to its pathogenicity and ecological trait differences. Moreover, we identified a gene set affected by genomic variation, and functional annotation of those genes indicated that some of them had potential roles in pathogenesis. CONCLUSIONS: This study provides an important resource for understanding the population structure, pathogenicity and evolutionary ecology of the nematode, and further analysis based on this study with geographically diverse B. xylophilus populations will greatly accelerate our understanding of the complex evolutionary/epidemic history of this emerging pathogen.

MFG-E8 regulates angiogenesis in cutaneous wound healing.

Our research group recently demonstrated that pericytes are major sources of the secreted glycoprotein and integrin ligand lactadherin (MFG-E8) in B16 melanoma tumors, and that MFG-E8 promotes angiogenesis via enhanced PDGF-PDGFRß signaling mediated by integrin-growth factor receptor crosstalk. However, sources of MFG-E8 and its possible roles in skin physiology are not well characterized. The objective of this study was to characterize the involvement of MFG-E8 in skin wound healing. In the dermis of normal murine and human skin, accumulations of MFG-E8 were found around CD31(+) blood vessels, and MFG-E8 colocalized with PDGFRß(+), αSMA(+), and NG2(+) pericytes. MFG-E8 protein and mRNA levels were elevated in the dermis during full-thickness wound healing in mice. MFG-E8 was diffusely present in granulation tissue and was localized around blood vessels. Wound healing was delayed in MFG-E8 knockout mice, compared with the wild type, and myofibroblast and vessel numbers in wound areas were significantly reduced in knockout mice. Inhibition of MFG-E8 production with siRNA attenuated the formation of capillary-like structures in vitro. Expression of MFG-E8 in fibrous human granulation tissue with scant blood vessels was less than that in granulation tissue with many blood vessels. These findings suggest that MFG-E8 promotes cutaneous wound healing by enhancing angiogenesis.

Pathogenesis of multiple lentigines in LEOPARD syndrome with PTPN11 gene mutation.

LEOPARD syndrome (LS) is an autosomal dominant condition with multiple anomalies, including multiple lentigines. LS is caused by mutations in PTPN11, encoding the protein tyrosine phosphatase, SHP-2. We report here 2 unrelated Japanese cases of LS with different PTPN11 mutations (p.Y279C and p.T468P). To elucidate the pathogenesis of multiple lentigines in LS, ultrastructural and immunohistochemical analyses of lentigines and non-lesional skin were performed. Numerous mature giant melanosomes in melanocytes and keratinocytes were observed in lentigines. In addition, the levels of expression of endothelin-1 (ET-1), phosphorylated Akt, mTOR and STAT3 in the epidermis in lentigines were significantly elevated compared with non-lesional skin. In in vitro assays, melanin synthesis in human melanoma cells expressing SHP-2 with LS-associated mutations was higher than in cells expressing normal SHP-2, suggesting that LS-associated SHP-2 mutations might enhance melanin synthesis in melanocytes, and that the activation of Akt/mTOR signalling may contribute to this process.

Current status of collaborative relationships between dialysis facilities and dental facilities in Japan: results of a nationwide survey.

BACKGROUND: Recent studies have reported an association between periodontal disease and mortality among dialysis patients. Therefore, preventive dental care should be considered very important for this population. In Japan, no systematic education has been undertaken regarding the importance of preventive dental care for hemodialysis patients--even though these individuals tend to have oral and dental problems. The aim of this study was to investigate the current state of collaborative relationships between hemodialysis facilities and dental services in Japan and also to identify strategies to encourage preventive dental visits among hemodialysis outpatients. METHODS: A nationwide questionnaire on the collaborative relationship between dialysis facilities and dental facilities was sent by mail to all medical facilities in Japan offering outpatient hemodialysis treatment. RESULTS: Responses were obtained from 1414 of 4014 facilities (35.2%). Among the 1414 facilities, 272 (19.2%) had a dental service department. Approximately 100,000 dialysis outpatients were receiving treatment at these participating facilities, which amounts to one-third of all dialysis patients in Japan. Of those patients, 82.9% received hemodialysis at medical facilities without dental departments. Only 87 of 454 small clinics without in-house dental departments (19.2%) had collaborative registered dental clinics. Medical facilities with registered dental clinics demonstrated a significantly more proactive attitude to routine collaboration on dental matters than facilities lacking such clinics. CONCLUSIONS: Our nationwide survey revealed that most dialysis facilities in Japan have neither an in-house dental department nor a collaborative relationship with a registered dental clinic. Registration of dental clinics appears to promote collaboration with dental facilities on a routine basis, which would be beneficial for oral health management in hemodialysis patients.

Role of endothelin-1/endothelin receptor signaling in fibrosis and calcification in nephrogenic systemic fibrosis.

Nephrogenic systemic fibrosis (NSF) is characterized by systemic fibrosis and abnormal calcification in patients with severe renal dysfunction. It is considered that gadolinium (Gd)-containing contrast agents used for magnetic resonance imaging trigger the development of NSF. However, the causative role of Gd and the mechanism of Gd-induced fibrosis and calcification in NSF are unknown. Recently, it has been known that endothelin-1 (ET-1)/ET receptor (ETR) signalling regulates fibrosis and calcification. The objective was to elucidate the role of ET-1/ETR signalling in Gd-induced fibrosis and calcification in NSF. First, we demonstrated that Gd enhanced proliferation and calcification of human adipose tissue-derived mesenchymal stem cells (hMSC) in vitro. Next, we examined the expression of ET-1 and ETR-A in hMSC using proliferation or calcification assay. ET-1 and ETR-A expression in hMSC treated with Gd were elevated. ET-1/ETR signalling inhibitor, bosentan, inhibited Gd-induced proliferation and calcification of hMSC. In addition, bosentan inhibited Gd-induced phosphorylation of ERK and Akt in hMSC. Plasma ET-1 levels of the patients were significantly higher than these of normal individuals and systemic sclerosis patients. In immunofluorescence staining, the expression of ETR-A in fibroblasts in dermal fibrosis lesion of NSF was increased. We conclude that Gd induces proliferation and calcification of hMSC via enhancement of ET-1/ETR signalling. Our results contribute to understand the pathogenesis of NSF.

Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs.

A series of 1-aryl-3,4-substituted-1H-pyrazol-5-ol derivatives was synthesized and evaluated as prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors to obtain a novel anti-prostate cancer drug. After modifying 1-(1H-benzimidazol-2-yl)-3,4-dimethyl-1H-pyrazol-5-ol (1), a hit compound found during random screening using a recombinant PCA-1/ALKBH3, 1-(1H-5-methylbenzimidazol-2-yl)-4-benzyl-3-methyl-1H-pyrazol-5-ol (35, HUHS015), was obtained as a potent PCA-1/ALKBH3 inhibitor both in vitro and in vivo. The bioavailability (BA) of 35 was 7.2% in rats after oral administration. As expected, continuously administering 35 significantly suppressed the growth of DU145 cells, which are human hormone-independent prostate cancer cells, in a mouse xenograft model without untoward effects.

[Two cases of cerebral amyloid angiopathy in which white matter lesions appearing after brain biopsy got improvement without immunotherapy].

The first case was a 75-year-old woman with intermittent sensory impairment of the left hand. FLAIR of the head MRI revealed hyperintensity along the pia mater in the right parieto-temporal lobe with few microbleeds. Our second case was a 78-year-old man who presented with motor aphasia. His MRI showed swollen cortex on FLAIR and cortical hemosiderosis on T2* weighted imaging of the right cerebral hemisphere. Pathological findings indicated the first case as cerebral amyloid angiopathy (CAA)-related inflammation and the second case as CAA. Additionally, after brain biopsy, widespread white matter lesions were detected in the area surrounding the biopsy site. However, both patients showed improvement without immunotherapy. Therefore, it is important to consider whether immunotherapy is required when white matter lesions appear in the area surrounding the biopsy site.

Efficacy of steroid therapy in the acute stage of anti-NMDAR and anti-MOG antibody overlapping encephalitis: a case report and literature review.

Background: Recently, cases of overlapping encephalitis caused by anti-N-methyl-D-aspartate receptor (anti-NMDAR) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies have been reported, and their clinical characteristics are gradually becoming clear. Acute-phase treatment typically involves the use of steroids, and although some studies have suggested that steroids can be effective, the extent of their efficacy has not yet been fully explored. Case presentation: We present the case of a 25-year-old man with anti-NMDAR and anti-MOG antibody overlapping encephalitis who showed considerable improvement after steroid treatment. To gain a deeper understanding of the efficacy of steroids in managing this condition, we conducted a literature review of cases of anti-NMDAR and anti-MOG antibody double-positive encephalitis that were treated with steroids during the acute phase. Thirteen cases were analyzed, including a new case diagnosed at our hospital. All patients showed improvement after receiving steroid treatment in the acute phase. Ten patients did not have any sequelae, and nine of them showed a rapid or major response during the acute phase. In contrast, three patients experienced sequelae (mild cognitive decline, visual impairment, and memory impairment, respectively), with their response to steroids in the acute phase being slow or limited. Relapses occurred in five patients, in one patient during steroid tapering, and in another two patients after cessation of steroids. Conclusion: Steroid therapy can be effective in the acute stage of anti-NMDAR and anti-MOG antibody overlapping encephalitis. A positive prognosis may be expected in patients who experience substantial improvement with steroid therapy during the acute phase.

[A case of multiple small cerebral infarcts in the cerebellum and bilateral cerebrum, diagnosed with amyloid angiopathy by brain biopsy].

An 82-year-old woman had been suffering from progressive forgetfulness and abnormal speech and behavior for One month. Findings of the MRI of the head indicated scattered small cerebral infarcts in the cerebellum and in bilateral cerebral cortex/subcortical white matter. After admission, she experienced a subcortical hemorrhage, and the percentage of small cerebral infarcts increased over time. Based on the suspicion of central primary vasculitis or malignant lymphoma, we performed a brain biopsy targeting the right temporal lobe hemorrhage site, and the patient was diagnosed with cerebral amyloid angiopathy (CAA). We conclude that CAA can cause multiple small progressive cerebral infarcts.

Happiness Detected by the Emotion Cognition System Is Associated with Burnout in an Information Technology Products and Services Trading Company.

(1) Background: Although many previous studies have found an association between burnout and emotions, none have examined the association between emotions detected by an emotion cognition system and burnout. The purpose of this study is to examine the relationship between the emotions detected by the emotion cognition system and burnout among workers. We hypothesized that burnout survivors are less likely to express their emotions as facial expressions. (2) Methods: One hundred and forty-one workers at an Information Technology (IT) products and services trading company were asked to take facial images for three months when they started and left work and responded to a burnout questionnaire once a month. Microsoft Azure was used to detect their emotions. (3) Results: Hierarchical multiple regression analyses revealed that happiness in Period 1 was significantly and negatively associated with burnout at Time 2. This association was also observed after the various covariates were included. However, burnout at Time 3 was not significantly related to any emotions in Period 1. (4) Conclusions: Happiness, as detected by the emotion cognition system, was associated with burnout immediately afterward.

[Primary central nervous system post-transplant lymphoproliferative disorder with few specific abnormal findings observed on MRI and in the cerebrospinal fluid].

A 60-year-old woman, who had a kidney transplant 16 years ago, was admitted to our hospital owing to cognitive decline and gait disturbances. She developed ataxia, consciousness disturbances, and myoclonus, and died two years after the onset of symptoms. No specific findings were observed on MRI or in the cerebrospinal fluid and blood analyses. The patient was diagnosed with post-transplant lymphoproliferative disorder (PTLD) based on the results of the autopsy. Pathological findings revealed proliferating monoclonal B cells in the perivascular space that was confined to the central nervous system. PTLD is a serious complication of transplantation. Furthermore, PTLD of the central nervous system usually presents as nodular lesions on MRI. When neurological symptoms appear after transplantation, it is necessary to consider PTLD as a differential diagnosis even if abnormal findings cannot be pointed out on MRI.

Rearrangements in the KcsA cytoplasmic domain underlie its gating.

A change of cytosolic pH 7 to 4 opens the bacterial potassium channel KcsA. However, the overall gating mechanism leading to channel opening, especially the contribution of the cytoplasmic domain, remains unsolved. Here we report that deletion of the cytoplasmic domain resulted in changes in channel conductance and gating behavior at pH 4 without channel opening at pH 7. To probe for rearrangements in the cytoplasmic domain during channel opening, amino acid residues were substituted with cysteines and labeled with a fluorophore (tetramethylrhodamine maleimide) that exhibits increased fluorescence intensity upon transfer from a hydrophilic to hydrophobic environment. In all cases channel open probability (P(o)) was approximately 1 at pH 4 and approximately 0 at pH 7. Major increases in fluorescence intensity were observed for tetramethylrhodamine maleimide-labeled residues in the cytoplasmic domain as pH changed from 7 to 4, which suggests the fluorophores shifted from a hydrophilic to hydrophobic environment. Dipicrylamide, a lipid soluble quencher, reduced the fluorescence intensities of labeled residues in the cytosolic domain at pH 4. These results reveal that a decrease in pH introduces major conformational rearrangements associated with channel opening in the KcsA cytoplasmic domain.

Channels formed by amphotericin B covalent dimers exhibit rectification.

Amphotericin B (AmB) is a widely used antifungal antibiotic with high specificity for fungi. We previously synthesized several covalently conjugated AmB dimers to clarify the AmB channel structure. Among these dimers, that with an aminoalkyl linker was found to exhibit potent hemolytic activity. We continue this work by investigating the channel activity of the dimer, finding that all channels comprised of AmB dimers show rectification. The direction of the dimer channel in the membrane depended on the electric potential at which the dimer channel was formed. On the other hand, only about half the monomer channels showed rectification. In addition, these channels were easily switched from a rectified to a nonrectified state following voltage stimulation, indicating instability. We propose a model to describe the AmB channel structure that explains why AmB dimer channels necessarily show rectification.

Fungus symbionts colonizing the galleries of the ambrosia beetle Platypus quercivorus.

Isolations were made to determine the fungal symbionts colonizing Platypus quercivorus beetle galleries of dead or dying Quercus laurifolia, Castanopsis cuspidata, Quercus serrata, Quercus crispula, and Quercus robur. For these studies, logs from oak wilt-killed trees were collected from Kyoto Prefecture, Japan. Fungi were isolated from the: (1) entrances of beetle galleries, (2) vertical galleries, (3) lateral galleries, and (4) the larval cradle of P. quercivorus in each host tree. Among the fungus colonies which appeared on YM agar plates, 1,219 were isolated as the representative isolates for fungus species inhabiting in the galleries based on their cultural characteristics. The validity of the visual classification of the fungus colonies was checked and if necessary properly corrected using microsatellite-primed PCR fingerprints. The nucleotide sequence of the D1/D2 region of the large subunit nuclear rRNA gene detected 38 fungus species (104 strains) of which three species, i.e., Candida sp. 3, Candida kashinagacola (both yeasts), and the filamentous fungus Raffaelea quercivora were isolated from all the tree species. The two yeasts were most prevalent in the interior of galleries, regardless of host tree species, suggesting their close association with the beetle. A culture-independent method, terminal restriction fragment length polymorphism (T-RFLP) analysis was also used to characterize the fungus flora of beetle galleries. T-RFLP patterns showed that yeast species belonging to the genus Ambrosiozyma frequently occurred on the gallery walls along with the two Candida species. Ours is the first report showing the specific fungi inhabiting the galleries of a platypodid ambrosia beetle.

[A case of central nervous system primary lymphomatoid granulomatosis with multiple vascular lesions in the spinal cord and brain].

A 71-year-old man was hospitalized because of low back pain and weakness in both lower limbs. He presented with fever and stiff neck, and his cerebrospinal fluid sample contained blood. MRI revealed intramedullary and epidural hemorrhages in the spinal cord. Microhemorrhages occurred frequently in the central nervous system over a short period. A brain biopsy was performed. The diagnosis was primary lymphomatoid granulomatosis (LYG) of the central nervous system (grade 2). As a result of lymphocytic infiltration to the vascular walls in LYG, hemorrhages occurred in multiple sites in the central nervous system. The biopsy of samples from the sites of microhemorrhages proved useful for diagnosis even in the absence of mass lesions.

Effect of Jersey cow defatted dry milk on salivary volume and composition in elderly persons†:†a pilot study.

The administration of Leu57-Leu58-His59-Lys60 (LLHK), Leu58-His59-Lys60 (LHK), and His59-Lys60 (HK) from ß-lactoglobulin C variant, which is specific to Jersey cow milk, has been shown to prevent and/or restore the age-dependent atrophy and functional decline of salivary glands by affecting gene expression in elderly rats. In this study, we investigated the effect of Jersey cow defatted milk on salivary volume and composition in elderly persons. Participants (aged 85 to 98, n = 8) were administered defatted dry milk from Jersey cows twice a day for 4 weeks. Before and after 4 weeks from the start of drinking, saliva was collected and weighed. Salivary cystatin S and amylase levels were analyzed by Western blotting. To assess the effect of Jersey cow defatted milk on taste perception, questionnaires were used. Salivary volume after oral administration of 40 g of Jersey cow defatted dry milk daily for 4 weeks was 1.8 times higher than that before administration. Salivary cystatin S and amylase levels significantly increased after administration of Jersey cow defatted dry milk. Moreover, all participants who had taste impairment reported improved taste perception after administration. The administration of Jersey cow defatted dry milk increased salivary volume and changed the composition of saliva in elderly persons. Furthermore, it improved taste perception. J. Med. Invest. 68 : 280-285, August, 2021.

Comparison of the intraocular pressure following an intravitreal triamcinolone acetonide injection for diabetic macula oedema in vitrectomised and non-vitrectomised eyes.

PURPOSE: To compare the intraocular pressure (IOP) after an intravitreal triamcinolone acetonide (IVTA) between vitrectomised and non-vitrectomised eyes in patients with diabetes and diabetic macular oedema (DME). DESIGN: Retrospective comparative study. METHODS: Medical records of 157 patients (157 eyes) with type 2 diabetes who received IVTA for DME were reviewed, and the best-corrected visual acuity, IOP and optical central retinal thickness (CRT) were compared preoperatively, at 1, 4, 12 and 24 weeks after IVTA between the vitrectomised and non-vitrectomised groups. RESULTS: IOP significantly increased at 1 (p<0.0001), 4 (p<0.0001), 8 (p<0.0001), 12 (p=0.0019), 16 (p=0.0006) and 20 weeks (p=0.0191) in the non-vitrectomised group, whereas a significant increase was only observed at 1 (p=0.0003) and 4 weeks (p=0.0006) in the vitrectomised group. ΔIOP, IOP changes from baseline, in the non-vitrectomised group was significantly higher than that in the vitrectomised group at 4 (p=0.0014), 8 (p=0.0081), 12 (p=0.0032) and 16 weeks (p=0.0038). No significant difference was observed in logMAR and CRT at any time point after IVTA between the two groups. CONCLUSIONS: After an initial IVTA, increased IOP and ΔIOP from the baseline IOP were significantly more frequently observed in the non-vitrectomised than that in the vitrectomised group. IVTA is a safer and more effective treatment option for DME in vitrectomised than that in non-vitrectomised eyes.