Treatment Effects of Switching to Faricimab in Eyes with Diabetic Macular Edema Refractory to Aflibercept.

Background and Objectives: Faricimab is a vascular endothelial growth factor A and angiopoietin-2 bispecific antibody. It is a novel therapeutic approach distinct from previous anti-vascular endothelial growth factor agents. This study aimed to evaluate the efficacy of switching from aflibercept to faricimab in the treatment of diabetic macular edema (DME) refractory to aflibercept, with a specific focus on the resolution of macular edema. Materials and Methods: The medical records of 29 eyes of 21 patients with DME that were refractory to intravitreal injections of aflibercept (IVAs) and who had completed the clinical follow-up of at least four intravitreal injections of faricimab (IVFs) were reviewed. The central retinal thickness (CRT), best-corrected visual acuity (BCVA), and the mean period (weeks) until the next injection were measured after the second-to-last IVA, first-to-last IVA, last IVA, and first to fourth IVFs following the transition to IVF. Results: The mean time from the first IVF to the assessment of effectiveness was significantly shorter than the time to the last IVA; however, no significant difference was found in the time from the second, third, and fourth IVFs to the assessment. The mean CRTs after the first and second IVFs were not significantly different from the CRT after the last IVA, but the mean CRT after the third and fourth IVFs was significantly thinner than that after the last IVA (p = 0.0025 and p = 0.0076, respectively). The mean BCVAs after the third and fourth IVFs significantly improved compared with that after the last IVA (p = 0.0050 and p = 0.0052, respectively). Conclusions: When switching the treatment to IVF for eyes with IVA-resistant DME, better treatment outcomes are achieved if IVF is performed three or more times.

Recovery From Central Retinal Artery Occlusion Accompanying Paracentral Acute Middle Maculopathy After COVID-19 Vaccination.

Although ocular complications following COVID-19 vaccination have been reported, particularly retinal vascular occlusion and uveitis, their definitive causal relationships remain uncertain. This report presents a case of central retinal artery occlusion (CRAO) with paracentral acute middle maculopathy (PAMM) developed one day after receiving Pfizer COVID-19 vaccine, with a favorable outcome. The patient experienced sudden vision loss in her left eye, and her vision dropped to hand motion the day after vaccination. The initial examination suggested CRAO, but optical coherence tomography (OCT) revealed PAMM. We administered intravenous d-mannitol and acetazolamide and performed ocular massage. Two days later, her corrected visual acuity improved to 0.4, and further improvement to 1.2 occurred after 16 days. To the best of our knowledge, no reports have documented CRAO with PAMM following mRNA COVID-19 vaccination. The relationship between COVID-19 vaccination and retinal vascular occlusion remains unknown, highlighting the need for further research.

Artificial intelligence-based model for predicting pulmonary arterial hypertension on chest x-ray images.

BACKGROUND: Pulmonary arterial hypertension is a serious medical condition. However, the condition is often misdiagnosed or a rather long delay occurs from symptom onset to diagnosis, associated with decreased 5-year survival. In this study, we developed and tested a deep-learning algorithm to detect pulmonary arterial hypertension using chest X-ray (CXR) images. METHODS: From the image archive of Chiba University Hospital, 259 CXR images from 145 patients with pulmonary arterial hypertension and 260 CXR images from 260 control patients were identified; of which 418 were used for training and 101 were used for testing. Using the testing dataset for each image, the algorithm outputted a numerical value from 0 to 1 (the probability of the pulmonary arterial hypertension score). The training process employed a binary cross-entropy loss function with stochastic gradient descent optimization (learning rate parameter, α = 0.01). In addition, using the same testing dataset, the algorithm's ability to identify pulmonary arterial hypertension was compared with that of experienced doctors. RESULTS: The area under the curve (AUC) of the receiver operating characteristic curve for the detection ability of the algorithm was 0.988. Using an AUC threshold of 0.69, the sensitivity and specificity of the algorithm were 0.933 and 0.982, respectively. The AUC of the algorithm's detection ability was superior to that of the doctors. CONCLUSION: The CXR image-derived deep-learning algorithm had superior pulmonary arterial hypertension detection capability compared with that of experienced doctors.

Japan-epiretinal membrane (J-ERM) registry: A prospective cohort study protocol investigating the surgical outcome of epiretinal membrane.

BACKGROUND: Epiretinal membrane (ERM) causes visual impairment such as reduction in visual acuity and metamorphopsia due to retinal traction. With the improvement of optical coherence tomography (OCT) and microincision vitrectomy surgery (MIVS), the surgery of ERM has significantly advanced. However, there have been no large-scale studies on the following: (1) how to evaluate visual impairment in ERM, (2) the relationship between OCT findings and visual function, (3) when is the optimal timing of surgery, and (4) the relationship between the surgical instruments as well as techniques and prognosis. The purpose of this study was to obtain evidence regarding these ERM surgeries. METHODS AND DESIGN: This is a prospective, multicenter cohort study of ERM surgery in Japan from March 1, 2023, to March 31, 2027 (UMIN000048472, R-3468-2). Patients who underwent ERM surgery during the study period and agreed to participate in this study will be included. The goal is to have a total of 5,000 eyes surgically treated for ERM. The following data will be collected: age, gender, medical history, subjective symptoms, visual function before and 6 and 12 months after surgery, clinical findings, OCT data, surgical technique, instruments used in surgery, and complications. DISCUSSION: The results of this study will support the surgical decisions and procedures in ERM practices.

Long-term follow-up of a young male who developed acute macular neuroretinopathy following COVID-19 vaccination.

This report presents the clinical findings and prognosis of a healthy male patient who developed acute macular neuroretinopathy after COVID-19 vaccination. Abnormal findings improved about 1 month after the onset and disappeared 3 months later. The subjective symptoms disappeared in 3 months, and no recurrence was observed for 1 year.

Retinal Pigment Epithelial Tears after Ex-PRESS Filtration Surgery in a Glaucoma Patient with a History of Ischemic Optic Neuropathy.

Background: To describe a case of retinal pigment epithelial tears (RPE tears) and serous retinal detachment (SRD) after Ex-PRESS filtration surgery for primary open-angle glaucoma (POAG) combined with ischemic optic neuropathy. Case Presentation. This case report involved a 69-year-old woman who underwent Ex-PRESS filtration surgery for right POAG. She had a history of systemic arteriosclerotic disease and subacute progressive visual field loss due to suspected ischemic optic neuropathy in her right eye. The right preoperative visual acuity was 0.7, and intraocular pressure (IOP) was 19 mmHg with maximum glaucoma eye drops. RPE detachment was not observed in the fundus. On day 9 after surgery, the IOP was 6 mmHg, and mild choroidal detachment was observed. On day 13, although IOP remained almost unchanged at 7 mmHg, bullous SRD was observed in the inferior retina, including the macula, and RPE tears were observed along the superior arcade vessel. While subretinal fluid gradually decreased with increasing IOP, tractional retinal folds persisted along the superior arcade, accompanied by macular degeneration. Conclusion: We experienced a case of RPE tears after Ex-PRESS filtration surgery. In addition to choroidal detachment in the setting of hypotony, a pathologic condition causing structural fragility of the RPE layer may contribute to the development of RPE tears.

Three-Year Follow-Up of Results of Intraocular Lens Fixation in Patients with Retinitis Pigmentosa.

This is a retrospective, consecutive, noncomparative case series of 6 eyes of 5 retinitis pigmentosa (RP) patients who had undergone pars plana vitrectomy (PPV) and intraocular lens (IOL) implantation. The aim of this case series was to report the long-term outcomes of PPV with IOL implantation in patients with RP). The surgical procedures, visual function, refractive error, corneal endothelial cell density, intraocular pressure, and retinal morphology were evaluated before and 3 years after the surgery. Six eyes of 5 RP patients that had undergone PPV and IOL implantation with or without suturing for lens dislocation were studied. The visual acuity was maintained or improved at 3 years after surgery in all 6 eyes. No intraoperative complications occurred in any of the cases. The mean deviation of the Humphrey Field Analyzer 10-2 program and the retinal morphology evaluated by optical coherence tomography did not show any abnormal changes before and after surgery. In two eyes, the postoperative refractive error was more myopic than the attempted refractive error. In conclusion, PPV with IOL implantation can be performed safely in RP patients, and the long-term visual acuity can be maintained.

Efficacy and safety of transdermal electrical stimulation in patients with nonarteritic anterior ischemic optic neuropathy.

BACKGROUND: No effective treatment for NAION with strong evidence has been established till date. The aim of this investigator-led, prospective, non-randomized, open-label, uncontrolled multi-center exploratory clinical trial is to evaluate the efficacy and safety of transdermal electrical stimulation (TdES) using skin electrodes in patients with NAION. METHODS: Five patients with monocular NAION underwent TdES (10-ms biphasic pulses, 1.0 mA, 20 Hz, 30 min) of the affected eye six times at 2-week intervals. The primary endpoint was the logarithm of the mini-mum angle of resolution (logMAR) visual acuity at 12 weeks compared with 0 weeks. The secondary endpoints were changes in the best-corrected logMAR visual acuity, Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity, and mean deviation (MD) of the Humphrey field analyzer (HFA) 10-2 and HFA Esterman test scores. Additionally, the safety of TdES was evaluated. RESULTS: LogMAR visual acuity improved by ≥ 0.1 in two eyes, and ETDRS visual acu-ity improved by ≥ 5 characters in one eye. The mean change in logMAR visual acuity from week 0 showed an increasing trend. The mean MD of HFA 10-2 showed no obvious change, while HFA Esterman score improved in four eyes. All patients completed the study according to the protocol, and no treatment-related adverse events were observed. CONCLUSIONS: TdES treatment may have improved visual acuity and visual field in some patients. Further sham-controlled study in larger cohort is needed on its effectiveness. TRIAL REGISTRATION: UMIN, UMIN000036220. Registered 15 March, 2019, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000041261 .

Effect of the First-Line Therapy with Osimertinib for a Metastatic Choroidal Tumor in Advanced-Stage Lung Cancer: A Case Report.

Although the advent of molecular-targeted drugs has improved the prognosis of various cancers, the long-term prognosis and side effects as the first-line therapy for metastatic choroidal tumors remain unclear. We describe a case in which the first-line therapy of osimertinib has shown long-term successful and minimum side effect responses for metastatic choroidal tumors in a patient with advanced-stage lung cancer. The patient was a 62-year-old man who complained of foggy vision and visual field defects in his left eye for 1 month. When he visited his local doctor, a serous retinal detachment was noted in the left eye, and he was referred to our hospital for further examination. The patient had no history of systemic disease. A fundus examination of his left eye showed a slightly elevated choroidal lesion along with the superior retinal vascular arcade. Optical coherence tomography showed a serous retinal detachment around the lesion. Fluorescein angiography showed that the site of the lesion had spotty and mottled hyperfluorescence in the early phase and ring hypofluorescence in the late phase. We suspected a metastatic choroidal tumor and performed a whole-body computed tomography scan, which indicated lung cancer and metastasis to the left iliac bone. The patient was referred to the department of respiratory medicine of our hospital, and after a thorough examination, a diagnosis of lung adenocarcinoma (stage IV-B, epidermal growth factor receptor [EGFR] gene mutation positive) was made. Treatment with osimertinib was initiated, and shrinkage of the primary tumor was observed. The elevated choroidal lesion and serous retinal detachment resolved after 2 months of treatment, and no recurrence was observed during the 20 months of treatment. The use of osimertinib as primary treatment for EGFR mutation-positive lung cancer was found to significantly reduce the size of metastatic choroidal tumors and to have a relatively long-lasting antitumor effect without serious ocular complications.

Alterations in choroidal vascular structures due to serum levels of vascular endothelial growth factor in patients with POEMS syndrome.

A higher serum vascular endothelial growth factor (VEGF) level can cause choroidal thickening in the choroid of patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. We aimed to determine whether fluctuations in serum VEGF levels affect choroidal vascular structures in patients with POEMS syndrome. This retrospective observational case series examined 17 left eyes of 17 patients with POEMS syndrome. Enhanced depth imaging optical coherence tomography (EDI-OCT) images were obtained, and serum VEGF levels were measured at baseline and 6 months after transplantation with dexamethasone (n = 6), thalidomide (n = 8), or lenalidomide (n = 3). EDI-OCT images were binarized using ImageJ software, and we calculated the areas of the whole choroid and the luminal and stromal areas. Subsequently, we determined whether the choroidal vascular structure had changed significantly between baseline and 6 months after treatment. Six months after treatment, serum VEGF levels and the whole choroid, luminal, and stromal areas had decreased significantly compared to the baseline values (all, P < 0.001). The mean luminal area to the whole choroidal area ratio at 6 months after treatment was 0.70 ± 0.03, which was significantly smaller than the ratio at baseline (0.72 ± 0.03; P < 0.001). Whole choroid and luminal area fluctuations were significantly positively correlated with fluctuations in serum VEGF levels (r = 0.626, P = 0.007 and r = 0.585, P = 0.014, respectively). Choroidal thickening induced by VEGF might be caused by increases in the choroidal vessel lumen area. These results may offer insights into the pathogenesis of POEMS syndrome and the role of serum VEGF in choroidal vascular structure, which may apply to other ocular diseases.

Exploratory clinical trial to evaluate the efficacy and safety of transdermal electrical stimulation in patients with central retinal artery occlusion.

PURPOSE: To evaluate the efficacy and safety of transdermal electrical stimulation (TdES) using skin electrodes in patients with central retinal artery occlusion (CRAO). METHODS: Five eyes of five patients with CRAO underwent TdES (10-ms biphasic pulses, 20 Hz, 30 min) six times at 2-week intervals. Only the affected eye was stimulated with 1.0-mA pulses in all patients. The primary endpoint was the best-corrected logMAR visual acuity. The secondary endpoints were changes in the best-corrected logMAR visual acuity, Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity, mean deviation of the Humphrey field analyzer (HFA) 10-2, and HFA Esterman test score. We also evaluated its safety. RESULTS: The logMAR visual acuity at 12 weeks was improved by 0.1 or more in two patients and was maintained in two patients compared to the baseline. No obvious changes in the mean logMAR visual acuity, ETDRS visual acuity, mean deviation, and HFA Esterman score were observed at 12 weeks compared to the baseline. All five enrolled patients completed the study according to the protocol. No treatment-related adverse events were observed during this study. CONCLUSION: In this study, logMAR visual acuity was slightly improved in two patients, confirming the safety of TdES. Since CRAO has no established treatment method, further research into the effects of TdES treatment in CRAO patients may be beneficial.

A novel Menin-MLL1 inhibitor, DS-1594a, prevents the progression of acute leukemia with rearranged MLL1 or mutated NPM1.

BACKGROUND: Mixed lineage leukemia 1-rearranged (MLL1-r) acute leukemia patients respond poorly to currently available treatments and there is a need to develop more effective therapies directly disrupting the Menin‒MLL1 complex. Small-molecule-mediated inhibition of the protein‒protein interaction between Menin and MLL1 fusion proteins is a potential therapeutic strategy for patients with MLL1-r or mutated-nucleophosmin 1 (NPM1c) acute leukemia. In this study, we preclinically evaluated the new compound DS-1594a and its salts. METHODS: We evaluated the preclinical efficacy of DS-1594a as well as DS-1594a·HCl (the HCl salt of DS-1594a) and DS-1594a·succinate (the succinic acid salt of DS-1594a, DS-1594b) in vitro and in vivo using acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) models. RESULTS: Our results showed that MLL1-r or NPM1c human leukemic cell lines were selectively and highly sensitive to DS-1594a·HCl, with 50% growth inhibition values < 30 nM. Compared with cytrabine, the standard chemotherapy drug as AML therapy, both DS-1594a·HCl and DS-1594a·succinate mediated the eradication of potential leukemia-initiating cells by enhancing differentiation and reducing serial colony-forming potential in MLL1-r AML cells in vitro. The results were confirmed by flow cytometry, RNA sequencing, RT‒qPCR and chromatin immunoprecipitation sequencing analyses. DS-1594a·HCl and DS-1594a·succinate exhibited significant antitumor efficacy and survival benefit in MOLM-13 cell and patient-derived xenograft models of MLL1-r or NPM1c acute leukemia in vivo. CONCLUSION: We have generated a novel, potent, orally available small-molecule inhibitor of the Menin-MLL1 interaction, DS-1594a. Our results suggest that DS-1594a has medicinal properties distinct from those of cytarabine and that DS-1594a has the potential to be a new anticancer therapy and support oral dosing regimen for clinical studies (NCT04752163).

Progress of iPS cell-based transplantation therapy for retinal diseases.

The discovery of induced Pluripotent Stem) (iPS) cells has instigated innovation in various fields, including ophthalmology. Cell therapy has shown tremendous progress in translational research on retinal diseases, including the first-in-human transplantation of autologous iPS cell-derived retinal pigment epithelium (RPE) cells for patients with age-related macular degeneration (AMD). Cell therapy for retinitis pigmentosa (RP) has also been developed. Retinal organoid and photoreceptor cell transplantation has been shown to incorporate into the degenerated host retina, forming synapses with host neurons and resulting in functional recovery. Based on preclinical data, first-in-human transplantation of iPS cell-derived retinal sheets has been conducted. In this review, we summarize the current progress in iPS cell-based retinal cell transplantation research for retinal diseases, addressing some remaining challenges and future prospects.

Optical coherence tomography findings in three patients with Werner syndrome.

BACKGROUND: Werner syndrome is a rare, autosomal recessive disorder characterised by premature aging. It is a typical hereditary progeroid syndrome that can be difficult to diagnose owing to its rarity and the similarity of some of its symptoms, such as juvenile cataracts, to other common ophthalmologic conditions. Early onset of bilateral cataracts is currently used as the ophthalmological feature for Werner syndrome; however, ophthalmologists often find performing a detailed examination of the medical history and genetic testing for Werner syndrome at the time of an ophthalmologic consultation challenging. If a unique ocular finding was observed on ocular examinations in cases of juvenile bilateral cataracts, we could consider Werner syndrome as a differential diagnosis.  CASE PRESENTATION: We documented the cases of three patients with Werner syndrome in whom thinning of the retina in the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) were observed using optical coherence tomography (OCT). Visual field tests revealed the loss of visual field mainly owing to glaucoma. The thinnig of the choroidal thickness (CT) in three patients was also observed using enhanced depth imaging (EDI)-OCT. CONCLUSIONS: Three patients have thinning of the RNFL, GCC, and choroidal thickness and the loss of visual field. These findings suggest the need for including Werner syndrome in the differential diagnosis when patients presenting with juvenile cataracts of unknown cause also show abnormal retinal and choroidal thinning in the OCT images.

Progression Rate of Visual Function and Affecting Factors at Different Stages of Retinitis Pigmentosa.

We reviewed medical records of 121 patients/235 eyes of typical retinitis pigmentosa (RP) patients who could be followed up for at least 5 years with the aim of investigating the long-term course of visual function progression at each RP stage and appropriate assessment methods. Patients were classified into three groups: mild RP (baseline mean deviation (MD) ≥ -5), moderate RP (-25 < baseline MD < -5), and late RP (baseline MD ≤ -25). Linear mixed-effect models were used to follow MD, the average retinal sensitivity of the central four points of the Humphrey field analyzer 10-2 program (S4), and visual acuity (VA) with increasing time. The associations among factors (baseline MD group, sex, hereditary form) and the interaction between each factor and time were also investigated. The mean reduction of the MD, S4, and VA for all patients was -0.37 dB/year, -0.25 dB/year, and 0.018/year, respectively. The moderate RP group had a faster progression than other groups in MD (-0.43 dB/year, p < 0.05). The moderate (-0.31 dB/year, p = 0.01) and late RP groups (-0.25 dB/year, p < 0.01) had faster progression than the mild RP group in S4. The late RP group had faster progression in VA than the other groups (0.03/year, p < 0.05). Females had a slower progression of the S4 (-0.15 dB/year, p = 0.02) and VA (0.01/year, p < 0.001) than males. The autosomal dominant group had a slower progression than the sporadic group in MD (-0.22 dB/year, p = 0.02); the autosomal dominant and autosomal recessive groups had a slower VA decline than the sporadic group (0.01/year, p = 0.03; 0.01/year, p = 0.04). Because the progression rates of VA and visual field test differed as per the RP stage, S4 and VA can also be useful assessment methods depending on the stage. Inheritance form and sex may affect the progression rate.

Case report: Partial visual recovery from incomplete traumatic optic nerve avulsion caused by a badminton shuttle.

Purpose: Blunt ocular trauma rarely results in optic nerve avulsion. Here, we report a case of incomplete optic nerve avulsion caused by the impact of a badminton shuttlecock. Observations: The patient was a 16-year-old healthy male. A badminton shuttlecock hit his right eye from a short distance. On his first visit to the local eye clinic, his visual acuity in the right eye was hand motion. About 4-mm hyphema in height was observed in the right eye. Three days after the injury, visual acuity improved to 20/50, but the intraocular pressure increased to 40 mmHg; hence, intraocular pressure (IOP)-lowering medication was initiated. Five days after the injury, although hyphema had decreased gradually, he noticed a worsening of vision and was referred to our department. In his right eye, visual acuity was reduced to finger-counting, IOP was 38 mmHg. Slit-lamp examination of the right eye revealed a dilated pupil, hyphema, and angle recession. Fundus examination revealed dilation of the central retinal vein and edematous changes around the optic nerve head. Optical coherence tomography showed a very deep depression of the optic nerve head and partial rupture of the optic nerve axons. B-mode ultrasonography showed hypolucency just posterior to the optic nerve head. Goldmann perimetry revealed a central visual field defect in the right eye. Computed tomography showed no signs of optic canal fracture. These findings suggest that incomplete optic nerve avulsion had occurred. We performed IOP-lowering and anti-inflammatory therapy. After treatment, visual acuity was restored to 20/50, and the deep depression of the optic nerve head recovered to an almost normal range. Conclusion and Importance: It was assumed that the impact of the badminton shuttlecock caused irreversible changes in the optic nerve head, but the visual function partially improved with IOP-lowering and anti-inflammatory therapy. Because eye injury in badminton can cause severe damage to visual function, every badminton player needs to wear an appropriate eye shield, and rules or guidelines to prevent untoward accidents are needed in badminton.

Randomized clinical trial comparing intravitreal aflibercept combined with subthreshold laser to intravitreal aflibercept monotherapy for diabetic macular edema.

To compare the efficacy and safety of intravitreal aflibercept with three loading doses + pro re nata regimen combined with subthreshold laser application to that of IVA monotherapy on eyes with diabetic macular edema. This was a phase 4 clinical trial with a prospective, randomized, and parallel investigator-driven protocol. Patients with DME were randomly assigned to the IVA monotherapy group (n = 25) or the IVA + SL combination therapy group (n = 26). The main outcome measures were the number of IVA injections and the changes in the best-corrected visual acuity (BCVA) and the central retinal thickness (CRT) at the final evaluation at 96 weeks. The mean number of IVA injections in the monotherapy group was 5.86 ± 2.43 and it was 6.05 ± 2.73 in the IVA + SL group at 96 weeks, and this difference was not significant (P = 0.83). The differences in the mean changes of the CRT (P = 0.17) and the BCVA (P = 0.31) were also not significant between the two groups throughout the follow-up period. We conclude that adjunct of SL to anti-VEGF therapy does not reduce the number of necessary intravitreal injections.

Long-term follow-up of retinal morphology and physiology after 2000 mg sildenafil overdose as a means of attempted suicide: a case report.

BACKGROUND: Few case reports have described sildenafil overdose, particularly ingestion of > 1000 mg, and overdose-induced changes in visual function remain unclear. We report retinal morphology, retinal sensitivity, and findings of electrophysiological evaluation over long-term follow-up in a case of sildenafil overdose (2000 mg). CASE PRESENTATION: Our patient developed visual abnormalities in the paracentral visual field accompanied by photophobia, decreased contrast sensitivity, and difficulty distinguishing colors in both eyes, 8 hours after the sildenafil overdose. These symptoms did not improve throughout the course, and although abnormalities of retinal morphology and sensitivity, as well as the electroretinogram findings showed slight improvement, the patient did not recover completely at 6-month follow-up. CONCLUSIONS: We observed that high-dose sildenafil ingestion leads to retinal toxicity; the ocular abnormalities may persist for at least 6 months. Optical coherence tomography, Humphrey perimetry, microperimetry, and multifocal electroretinography are useful to quantitatively monitor temporal changes.

Sodium-Glucose Co-Transporter 2 Inhibitors Reduce Macular Edema in Patients with Diabetes mellitus.

PURPOSE: To determine the efficacy of systemic sodium-glucose co-transporter 2 inhibitors (SGLT2i) on diabetic macular edema (DME). METHODS: The medical records of patients with DME with a central retinal thickness (CRT) ≥320 µm in men and 305 µm in women, more than 6 months after the initiation of diabetes mellitus treatment, were reviewed. The CRT and best-corrected visual acuity (BCVA) were evaluated before and after the initiation of systemic SGLT2i and non-SGLT2i treatments. RESULTS: There were 24 eyes of 19 patients with DME that were treatment naïve or had not received treatments for the DME within four months before the initiation of SGLT2i. In these patients, the BCVA had a 0.31 ± 0.39 logarithm of the minimum angle of resolution (logMAR) units at the baseline, and it did not improve significantly at 0.26 ± 0.29 logMAR units after the initiation of SGLT2i (p = 0.56). However, the SGLT2i treatment significantly reduced the CRT from 423.3 ± 79.8 µm to 379.6 ± 69.5 µm (p = 0.0001). In the same evaluation of 19 eyes of 14 patients with DME that were initiated with non-SGLT2i agents, there was no significant difference between the baseline BCVA and the BCVA after the initiation of non-SGLT2i (p = 0.47). The CRT increased significantly after the initiation of non-SGLT2i (p = 0.0011). In three eyes in which the SGLT2i treatments were administered at the time of anti-vascular endothelial growth factor (VEGF) treatments, the anti-VEGF treatment alone had only a limited effect on the DME, but the reduction in the DME was enhanced after the addition of SGLT2i. CONCLUSIONS: These findings indicate that systemic SGLT2i can reduce DMEs, and they suggest that SGLT2i may be an additional treatment option to anti-VEGF treatments for eyes with DMEs.

Evaluating the efficacy and safety of transdermal electrical stimulation on the visual functions of patients with retinitis pigmentosa: a clinical trial protocol for a prospective, multicentre, randomised, double-masked and sham-controlled design (ePICO trial).

INTRODUCTION: Previously, we conducted a clinical trial to evaluate the safety and efficacy of transdermal electrical stimulation (TdES) with skin electrodes to improve the visual functions in patients with retinitis pigmentosa (RP). No adverse events were related to the treatment during follow-up examinations, and TdES significantly improved the mean visual acuity and visual field sensitivity. METHODS AND ANALYSIS: We developed a study protocol for a prospective, multicentre, randomised, double-masked and sham-controlled clinical trial, planned to commence on June 2021. We intend to compare the maintenance or improvement in best-corrected visual acuity, and safety of TdES using skin electrodes between patients with RP and the sham group. The primary endpoint comprises the superiority of the logarithm of the minimum angle of resolution (logMAR) visual acuity change at week 24 from baseline in the treatment and sham groups. Secondary endpoints involve the comparison of the treatment and sham groups at week 24 for the logMAR visual acuity, early treatment diabetic retinopathy study visual acuity, the mean deviation value of Humphrey field analyser 10-2, monocular Humphrey Esterman visual field test score, ellipsoid zone length, central foveal thickness and 25-item National Eye Institute Visual Function Questionnaire score. We intend to enrol 50 patients from three Japanese institutions within 1 year and follow them up for 1 years. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review board at the Chiba University Hospital and two other institutions, and was registered with the Japan Registry of Clinical Trials on 17 May 2021. The trial will be conducted in accordance with the principles of the Declaration of Helsinki, and is in accordance with Good Clinical Practice standards. The findings will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: JRCT2032210094.