An Autopsy Case of Elderly Onset Brainstem Acute Disseminated Encephalomyelitis.

Acute disseminated encephalomyelitis (ADEM), which is a disease that causes multifocal inflammatory demyelination of the central nervous system, occurs predominantly in children and young adults. We report an autopsy case of an elderly man with brainstem ADEM that progressed over a period of about 3 months. An 82-year-old man developed disturbance of consciousness, dysphagia, and ataxic gait over a period of about 3 months. He was admitted to another hospital for aspiration pneumonia and recovered but was transferred to our hospital due to prolonged disturbance of consciousness. The patient was able to follow simple commands but had a tendency to somnolence. In addition to meningeal stimulation signs, the patient had left-dominant upper and lower limb ataxia and right-dominant limb spasticity. Brain FLAIR/T2-weighted imaging showed high-intensity lesions from the brainstem to the middle cerebellar peduncle bilaterally, medulla oblongata and upper cervical spinal cord, and T1-weighted imaging revealed contrast-enhanced lesions in the left middle cerebellar peduncle and cervical spinal cord. Although spinal fluid examination revealed elevated proteins, other laboratory tests indicated no evidence of infection, vasculitis, collagen diseases or tumors, and anti-ganglioside, anti-AQP4 and anti-MOG antibodies were negative. After admission, the patient again developed aspiration pneumonia, which progressed to acute respiratory distress syndrome, and he died on the 15th day of hospitalization. Autopsy findings indicated acute and subacute demyelination mainly in the brainstem and cerebellum, and perivascular lymphocyte and macrophage infiltration in the areas of demyelination. A postmortem diagnosis of ADEM was made based on the generally monophasic course of the disease and the absence of regenerating myelinated sheaths. There are very few reports of elderly patients with brainstem ADEM. ADEM should be considered as a differential diagnosis in patients with brainstem encephalitis.

Linear association between aging and decreased blood thiol antioxidant activity in patients with cataract.

We comprehensively assessed the roles of systemic redox markers by including both prooxidant and antioxidant markers in 121 Japanese subjects (mean ±â€…SD age, 70 ±â€…11 years; 38 men) with no ocular pathology except age-related cataract. Serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured using the diacron reactive oxygen metabolite (dROM), biologic antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free-radical analyzer. Univariate analyses suggested that older age, higher pulse rate, worse best-corrected visual acuity (BCVA), higher intraocular pressure, and higher cataract grade were associated with a lower SH level. Scatterplots revealed virtually linear associations between age and the SH level (estimate, -4.4 µM/year). Multivariate analyses suggested that older age, higher systolic blood pressure, and worse BCVA were associated with a lower SH level. Neither the univariate nor multivariate analyses, except between female sex and higher dROM level, were associated with the dROM or BAP level. A lower serum SH level was the driver of aging itself and age-related decline in VA due to cataract. The serum SH level may be an excellent predictor of aging status in each subject.

Refractive Status in Eyes Implanted with Toric and Nontoric Intraocular Lenses during Combined Cataract Surgery and Microhook Ab Interno Trabeculotomy.

PURPOSE: To compare the refractive status between eyes implanted with toric and nontoric intraocular lenses (IOLs) during combined cataract surgery and microhook ab interno trabeculotomy (µLOT), a minimally invasive glaucoma surgery (MIGS). METHODS: Twenty eyes of 20 patients who had open-angle glaucoma, cataract, and preexisting regular corneal astigmatism exceeding 1.5 diopters (D) and underwent combined µLOT and phacoemulsification were recruited retrospectively. Ten eyes were implanted with a toric IOL and 10 eyes with a nontoric IOL. The primary outcomes were the uncorrected visual acuity (UCVA) and refractive cylinder at 3 months postoperatively. RESULTS: The mean UCVA of the toric IOL group (logarithm of the minimum angle of resolution (logMAR), 0.23 ± 0.25) was significantly better than that of the nontoric IOL group (logMAR, 0.45 ± 0.26) at 3 months postoperatively (p < 0.05). The mean absolute residual refractive cylinder of the nontoric IOL group (2.25 ± 0.62 D) was significantly greater than that of the toric IOL group (1.30 ± 0.68 D) (p < 0.05). Postoperatively, 60% of eyes in the toric IOL group and 10% in the nontoric IOL group had an absolute refractive astigmatism level of 1.5 D or less. Surgically induced astigmatism (0.77 ± 0.43 D for toric group and 0.60 ± 0.32 D for nontoric group) and IOP reduction (33.9 ± 15.6% for toric group and 29.4 ± 11.7% for nontoric group) were not different between groups. CONCLUSIONS: Use of toric IOL during combined cataract surgery and µLOT is possible and better than not, but physician should prevent their patient of persisting residual astigmatism. The study was registered at https://www.umin.ac.jp/, and the clinical trial accession number is https://clinicaltrials.gov/ct2/show/UMIN000043141.

Saccharopinuria accompanied by hyperammonemia and hypercitrullinemia presented with elderly-onset epilepsy, progressive cognitive decline, and gait ataxia.

We report a case of saccharopinuria with hyperammonemia and hypercitrullinemia in a Japanese woman who presented with elderly-onset epilepsy, progressive cognitive decline, and gait ataxia. Blood amino acid analysis revealed an increase in citrulline, cystine, and lysine levels, and urine amino acid analysis showed increased citrulline and cystine levels. Urine metabolomics revealed an increased saccharopine level, leading to the definitive diagnosis of saccharopinuria. In western blots of liver biopsy samples, normal citrin levels were observed, suggesting that adult-onset citrullinemia type 2 (CTLN2) was not present. In addition, decreased argininosuccinate synthetase (ASS) levels were observed, and ASS1 gene, a causative gene for citrullinemia type 1 (CTLN1), was analyzed, but no gene mutations were found. Because the causes of hypercitrullinemia were not clear, it might be secondary to saccharopinuria. Muscle biopsy findings of the biceps brachii revealed diminished cytochrome c oxidase (COX) activity, mitochondrial abnormalities on electron microscopy and p62- positive structures in immunohistochemical analyses. Saccharopinuria is generally considered a benign metabolic variant, but our case showed elevated lysine and saccharopine levels causing ornithine circuit damage, mitochondrial dysfunction, and autophagy disorders. This may lead to so far unknown neurological disorders.

Sympathetic ophthalmia after 27-G pars plana vitrectomy.

BACKGROUND: Sympathetic ophthalmia (SO) is a bilateral diffuse uveitis that can arise after ocular trauma or ocular surgery in the inciting eye. Pars plana vitrectomy (PPV) is one of the risk factors for SO. Several reports have described SO developing after 23- and 25-G PPV, but none have described SO occurring after 27-G PPV. We describe herein a case of SO after 27-G PPV for rhegmatogenous retinal detachment. CASE PRESENTATION: A 42-year-old woman presented with visual disturbance in the right eye. Best-corrected visual acuity (BCVA) was 6/200 in the right eye. Fundus examination revealed off-macula retinal detachment with retinal tears at both ends of retinal lattice degeneration at the temporal-oven peripheral retina of the right eye. We therefore performed 27-G sutureless PPV on the right eye. After 12 days, the retina was reattached, and BCVA improved to 6/30 in the right eye. Fifteen days postoperatively, she experienced headache and reduced vision in both eyes. Symptoms gradually worsened, and she visited our hospital 21 days postoperatively. BCVA was 6/30 in the right eye and 6/15 in the left eye. Slit-lamp examination revealed uveitis in the anterior chambers of both eyes, and fundus examination showed papillitis and subretinal detachment at the posterior poles of both eyes. Optical coherence tomography revealed subretinal fluid in the maculae of both eyes and fluorescein angiography showed multiple hyperfluorescent leakage sites in the retinal pigment epithelium. Cerebrospinal fluid examination showed pleocytosis and human leukocyte antigen testing showed expression of the DR04 phenotype; therefore, the patient was diagnosed with SO. She was treated with steroid therapy, and her visual disturbance subsided and the subretinal fluid improved as well. Her BCVA was 6/15 for the right eye and 6/5 for the left eye 93 days after the initial surgery. CONCLUSION: The present case shows that even if the sclerotomy site of 27-G PPV is small, there is still a risk of SO occurring in the eyes of patients who underwent transconjunctival vitrectomy. Ophthalmologists should recognize SO as complication of 27-G PPV and carry out proper management as early as possible.

Effect of Toric Intraocular Lens Implantation on Visual Acuity and Astigmatism Status in Eyes Treated With Microhook Ab Interno Trabeculotomy.

PRCIS: Use of toric intraocular lenses is a reasonable option for better visual outcomes when a combined minimally invasive glaucoma surgery (MIGS) and cataract surgery is performed in eyes with corneal astigmatism. PURPOSE: To assess the efficacy of toric intraocular lenses (IOLs) in combined cataract and MIGS, visual and refractive outcomes were compared between eyes implanted with nontoric and toric IOLs during microhook ab interno trabeculotomy triple procedures. METHODS: Glaucomatous eyes with preexisting corneal astigmatism exceeding -1.5 D implanted with nontoric (n=10) or toric (n=10) IOLs were evaluated retrospectively. The uncorrected visual acuity (UCVA) and refractive astigmatism preoperatively and 3 months postoperatively were compared. RESULTS: Preoperatively, the groups had similar logarithm of the minimum angle of resolution (logMAR) UCVAs and refractive astigmatism. Postoperatively, the logMAR UCVA (toric, 0.07±0.07; nontoric, 0.33±0.30; P=0.0020) was significantly better and the refractive astigmatism (toric, -0.63±0.56 D; nontoric, -1.53±0.74 D; P=0.0110) significantly less in the toric group. The toric group had postoperative improvements in the logMAR UCVA (-0.58, P=0.0039) and refractive astigmatism (+1.45 D, P=0.0195). Vector analyses showed the postoperative centroid magnitude of refractive astigmatism was less in the toric group (0.23 D at 83 degrees) than the nontoric group (1.03 D at 178 degrees). Postoperatively, 70% of eyes in the toric group had 1.0 D or less refractive astigmatism compared with 10% in the nontoric group. Surgically induced astigmatism (nontoric group, 0.62 D at 10 degrees; toric group, 0.50 D at 113 degrees) and intraocular pressure reduction (22% in both groups) did not differ between groups. CONCLUSIONS: Better visual outcomes may be achieved with toric IOLs when a combined MIGS/cataract surgery is performed in eyes with corneal astigmatism.

Efficacy and Safety of Intravitreal Aflibercept Injection in Japanese Patients with Neovascular Glaucoma: Outcomes from the VENERA Study.

INTRODUCTION: Neovascular glaucoma is characterized by neovascularization of the iris and anterior angle chamber. Intravitreal anti-vascular endothelial growth factor agents may decrease intraocular pressure (IOP) and improve neovascularization. The VENERA study assessed the efficacy and safety of intravitreal aflibercept (IVT-AFL) in patients with neovascular glaucoma. METHODS: This was a 5-week, single-arm, nonrandomized, open-label, phase 3 study performed at 7 study sites in Japan that enrolled Japanese patients with anterior segment neovascularization and IOP > 25 mmHg who had not undergone (within 30 days prior), nor were imminently scheduled to undergo (within 8 days following) intraocular surgeries, including panretinal photocoagulation (PRP). Patients received background therapy plus 2 mg IVT-AFL at baseline. Background therapy with systemic IOP-lowering drugs was prohibited for 3 days before day 1 and until IOP evaluation at week 1. The primary endpoint was the change in IOP from baseline to week 1 and the secondary endpoint was the proportion of patients with an improvement of ≥ 1 grade of neovascularization of the angle (NVA) from baseline to week 1. RESULTS: Sixteen patients received treatment (full analysis set); the per-protocol set comprised 15 patients. The mean IOP decreased from 34.1 mmHg at baseline to 25.8 mmHg at week 1 (mean change, -8.3 mmHg [95% confidence interval; CI -12.2 to -4.4; P = 0.0004]). At week 1, 81.3% of patients had an improvement in the grade of neovascularization of the iris (NVI) and 50.0% of patients had an improvement in NVA grade. The proportion of patients with controlled IOP (≤ 21 mmHg) was 43.8% (95% CI 19.8-70.1) at week 1, and increased to 56.3% at week 2 and 86.7% at week 5. The most common ocular treatment-emergent adverse event was eye pain, which occurred in 4 patients (25.0%). CONCLUSIONS: IVT-AFL was associated with statistically significant and clinically meaningful IOP reductions, without concomitant use of systemic IOP-lowering drugs or PRP. The safety profile was consistent with the known safety profile of IVT-AFL. These findings supplement those from the previous VEGA study, and suggest that IVT-AFL may be a potential treatment option for patients with neovascular glaucoma. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT03639675.

Comparison of anterior chamber flare among different glaucoma surgeries.

PURPOSE: To compare postsurgical anterior chamber flare (ACF) among conventional (trabeculectomy, LEC) and novel (EX-PRESS Shunt, EXP) filtration surgeries and microhook ab interno trabeculotomy (µLOT), a novel minimally invasive glaucoma surgery (MIGS). SUBJECTS AND METHODS: This retrospective study included 125 primary open angle glaucoma eyes (89 consecutive subjects) treated with µLOT (n=38), LEC (n=12), or EXP (n=75). The intraocular pressure (IOP), numbers of antiglaucoma medication, and ACF at preoperatively and 2 weeks; 1, 3, and 6 months postoperatively were compared among the surgical groups using a mixed-effects regression model. RESULTS: The postoperative IOP (p<0.0001) and medication use were significantly (p<0.0001) lower in the LEC and EXP groups than with µLOT for up to 6 months postoperatively. The ACF differed significantly (p=0.0004) among groups; the ACF was significantly higher (p=0.0097, post-hoc Student's t-test) with µLOT (33.6±52.8 pc/msec) than the EXP (15.7±19.9 pc/msec) at 2 weeks and was significantly (p=0.0111, post-hoc t-test) lower with µLOT (7.9±2.0 pc/msec) than LEC (12.0±6.1 pc/msec) at 6 months. CONCLUSION: Considering our observation, although its clinical significance is unclear, not all MIGS are minimally invasive regarding early postsurgical inflammation.

The Role of Single-Layered Flap in Temporal Inverted Internal Limiting Membrane Flap Technique for Macular Holes: Pros and Cons.

PURPOSE: To assess the safety and effectiveness of the single-layered inverted internal limiting membrane (ILM) flap technique for treating chronic, large, or highly myopic macular holes (MHs). METHODS: The medical records of 20 eyes of 20 consecutive Japanese patients with large MHs (n=6) (minimal diameter, >400 µm), chronic MHs (n=2) (symptom duration, >24 months), MHs in high myopia (n=11) (axial length, >26 mm), and MHs in a patient unable to maintain prone positioning postoperatively (n=1) were reviewed retrospectively. All patients underwent 25-gauge pars plana vitrectomy and the temporal inverted ILM flap technique. A semicircular ILM notch was made temporally two disc diameters from the MH using a 25-gauge knife, and the ILM was peeled temporally to create a semicircular ILM flap using a 25-gauge forceps. The single-layered ILM flap was inverted in a nasal direction to cover the MH. When an epiretinal membrane (ERM) was present, it was peeled before the ILM flap was inverted. RESULTS: The MHs closed successfully in all (100%) eyes postoperatively. In the MHs associated with an ERM, after hole closure, gradual foveal deformation occurred in both the area from which the ILM was not peeled and the ILM flap inverted side. CONCLUSIONS: The single-layered inverted ILM flap technique, a simple surgery to treat MHs, provides scaffolding for retinal gliosis and may facilitate bridge formation between the walls of the MH under the flap. Considering the 100% success rate of MH closure, this technique seems to be effective and safe for treating chronic, large, or highly myopic MHs and MHs in patients unable to maintain postoperative prone positioning. In the MHs associated with ERMs, gradual foveal deformation was observed after ERM peeling. Further studies are needed to minimize surgical complications and understand the mechanism of this technique. This trial is registered with UMIN000035091.

TEMPORAL INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE FOR A MACULAR HOLE PATIENT UNABLE TO MAINTAIN POSTOPERATIVE PRONE POSITIONING.

PURPOSE: To report the surgical technique and efficacy of the temporal inverted internal limiting membrane (ILM) flap technique for a patient with an idiopathic macular hole (MH) who is unable to maintain postoperative prone positioning. METHODS: Case report. RESULTS: A 73-year-old man with a Stage III MH in his left eye was scheduled to undergo surgery. Owing to his inability to maintain postoperative prone positioning for continuous placement of a transdermal bladder catheter after radical cystoprostatectomy to treat urinary bladder cancer, he underwent pars plana vitrectomy combined with the temporal inverted ILM flap technique and intraocular sulfur hexafluoride gas tamponade. The technique included ILM peeling at a temporal area of the macula to create one 2-disk-diameter semicircular ILM flap and inversion of the ILM flap nasally to cover the MH. Optical coherence tomography showed that MH closure started from the top of the MH just beneath the covered ILM flap; the closure process gradually extended toward the bottom of the MH. The well-aligned fovea recovered in 5 weeks postoperatively. The visual acuity was 20/200 preoperatively and improved to 20/50 postoperatively. CONCLUSION: The temporal inverted ILM flap technique, a simple surgery to treat MHs, provides scaffolding for retinal gliosis and may facilitate bridge formation between the walls of the MH beneath the flap. The procedure may be a good option to achieve MH closure without postoperative prone positioning.

Lack of association of LOXL1 gene variants in Japanese patients with central retinal vein occlusion without clinically detectable pseudoexfoliation material deposits.

PURPOSE: A possible association has been reported between exfoliation syndrome (EX) and various ocular and systemic vascular disorders; however, it is unclear if there is an association between EX and central retinal vein occlusion (CRVO). Because latent deposits of exfoliation materials might not be recognized during slit-lamp examination, an ocular biopsy is required to establish a precise diagnosis. We evaluated a possible association between EX and CRVO using lysyl oxidase-like 1 (LOXL1) gene variants as alternative markers for EX. METHODS: The allelic and genotypic frequencies of three LOXL1 variants (rs1048661, rs3825942, and rs2165241) were determined in 68 consecutive Japanese patients with CRVO [15 with exfoliation syndrome (EX+) and 53 without exfoliation syndrome (EX-)] and 90 control patients with cataract without EX (CT). RESULTS: The frequencies of the rs1048661 and rs3825942 variants showed borderline difference between the CRVO and CT groups (p = 0.04085 and p = 0.06088, respectively, for allelic frequencies, and p = 0.06838 and p = 0.03482, respectively, for genotypic frequencies). Compared with the CT group, subgroup analysis showed that the CRVO EX+ group had significant differences in the allelic and genotypic frequencies of rs1048661 (p = 0.0006447 and p = 0.0001392, respectively) and had borderline differences in the allelic and genotypic frequencies of rs3825942 (p = 0.03403 and p = 0.07341, respectively), while the CRVO EX- group did not (p = 0.1324-0.6306). Subgroup analysis showed that the frequencies of rs2165241 did not differ between the CRVO and CT groups. CONCLUSIONS: When the LOXL1 variants were used as disease markers for clinically undetectable EX, there was no association between CRVO and EX. The results suggested that the LOXL1 variants, which are well-established markers for EX, are not likely genetic markers for CRVO in Japanese subjects.

Visual function and vision-related quality of life after vitrectomy for epiretinal membranes: a 12-month follow-up study.

PURPOSE: Toevaluate the effect of removing epiretinal membranes (ERMs) on visual function and vision-related quality of life (VR-QOL) for 12 months postoperatively. METHODS: Idiopathic ERMs were removed during vitrectomy in 26 eyes. The VR-QOL was evaluated using a self-administered 25-item National Eye Institute Visual Function Questionnaire before (baseline) and 3 and 12 months postoperatively. During the same periods, the best-corrected visual acuity (BCVA), central macular thickness (CMT), and metamorphopsia score were recorded. RESULTS: At baseline and months 3 and 12, the logMAR BCVAs (mean ± SEM) were 0.41 ± 0.05, 0.17 ± 0.04 (P = 0.0001 versus baseline), and 0.10 ± 0.03 (P < 0.0001 versus baseline, P = 0.0016 versus month 3), respectively; the CMTs (µm) were 402 ± 18, 312 ± 9 (P < 0.0001 versus baseline), and 300 ± 7 (P < 0.0001 versus baseline, P = 0.0544 versus month 3); and the metamorphopsia scores were 202 ± 29, 137 ± 27 (P = 0.0186 versus baseline), and 108 ± 26 (P = 0.0005 versus baseline, P = 0.0218 versus month 3). In 23 (88%) of 26 eyes, the BCVA improved more than 0.1 logMAR unit at month 12. The improved BCVA was correlated with improvements in two subscales (r = -0.405 to -0.574, P = 0.0041-0.0427) at month 3; the improved metamorphopsia score was correlated with the improved composite score (r = -0.552, P = 0.0058) and three subscales (r = -0.458 to -0.507, P = 0.0113-0.0219) at month 12. CONCLUSIONS: Removing ERMs improved visual function, anatomy, and the VR-QOL. Three months postoperatively, the improved BCVA was the most important factor related to the improved VR-QOL, although the simultaneous cataract surgery might have had a confounding effect. The improved metamorphopsia was the important factor associated with improved VR-QOL 12 months postoperatively.(www.umin.ac.jp/ctr number, UMIN000000617).

Multiplex cytokine analysis of aqueous humor in eyes with primary open-angle glaucoma, exfoliation glaucoma, and cataract.

PURPOSE: To measure levels of various inflammatory cytokines in the aqueous humor of patients with primary open-angle glaucoma (POAG), exfoliation glaucoma (EXG), and senile cataract. METHODS: Aqueous humor samples were obtained from 64 eyes of 64 Japanese subjects (POAG, 20 eyes; EXG, 23 eyes; and cataract, 21 control eyes). The levels of eight cytokines including interleukin (IL)1-ß, IL-6, IL-8, transforming growth factor (TGF)-ß1, tumor necrosis factor (TNF)-α, serum amyloid A (SAA), migration inhibitory factor (MIF), and vascular endothelial growth factor (VEGF)-A were estimated using the multiplex bead immunoassay technique. RESULTS: Compared with the cataract group, the levels of TGF-ß1, IL-8, and SAA were significantly higher in aqueous humor samples from the POAG (5.0-fold, 2.3-fold, and 11.9-fold, respectively) and EXG (12.5-fold, 4.0-fold, and 18.3-fold, respectively) groups. Except for a significant decrease in the IL-6 level in the POAG (0.23-fold) group, no other cytokine levels differed in the POAG and EXG groups compared with the cataract group. The levels of TGF-ß1, IL-8, and SAA were positively correlated with each other (ρ = 0.723-0.786; P < 0.0001), the intraocular pressure (IOP) (ρ = 0.392-0.662; P < 0.0001-0.0019), and the number of glaucoma medications (ρ = 0.478-0.659; P < 0.0001-0.0001). CONCLUSIONS: Cytokine networks including TGF-ß1, IL-8, and SAA in aqueous humor may have critical roles in IOP elevations in patients with open-angle glaucoma.

Topical dexamethasone-cyclodextrin microparticle eye drops for diabetic macular edema.

PURPOSE: To test the safety and efficacy of topical 1.5% dexamethasone aqueous eye drops with cyclodextrin microparticles for diabetic macular edema (DME). METHODS: Nineteen eyes of 19 consecutive patients with DME were administered dexamethasone-cyclodextrin eye drops three or six times a day for 4 weeks and then observed for 4 weeks without treatment. Visual acuity, intraocular pressure, and spectral domain optical coherent tomography-measured central macular thickness recordings at weeks 0 (baseline), 4, and 8. These parameters were compared using Bonferroni-corrected paired t-tests. RESULTS: At weeks 0, 4, and 8, logMAR visual acuity (mean ± SD) was 0.52 ± 0.41, 0.37 ± 0.40 (P = 0.0025 vs. baseline), and 0.45 ± 0.41, respectively; central macular thickness (µm) was 512 ± 164, 399 ± 154 (P = 0.0016 vs. baseline), and 488 ± 172 (P = 0.0116 versus week 4), respectively; and intraocular pressure (mm Hg) was 15.2 ± 3.1, 17.4 ± 4.2 (P = 0.0015 vs. baseline) and 15.8 ± 4.0, respectively. At week 4, in 12 (63%) of 19 eyes, central macular thickness had decreased more than 10%, and the mean change was -20% (-65% to +10%). In 14 of 19 eyes (74%) visual acuity (logMAR) had improved more than 0.1 at week 4. No subjects showed severe adverse effects related to the eye drops. CONCLUSIONS: Based on this short pilot study, topical dexamethasone-cyclodextrin eye drops are well tolerated, decrease central macular thickness, and improve visual acuity in DME. The results encourage comparative studies between dexamethasone cyclodextrin microparticle eye drops and other treatments for DME. (http://www.umin.ac.jp/ctr number, UMIN000001790.).