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Abstract Aims/Introduction Severe diabetic macular edema (DME) is often resistant to anti‐vascular endothelial growth factor therapy. Steroids are particularly effective at reducing edema by suppressing inflammation; they are also used as an alternative to expensive anti‐vascular endothelial growth factor therapy in some patients. Therefore, the use of steroids in DME reflects an unmet need for anti‐vascular endothelial growth factor therapy. Notably, triamcinolone acetonide (TA) injections are widely used in Japan. Here, we evaluated the frequency of TA as an indicator of the efficacy of sodium–glucose cotransporter 2 inhibitors (SGLT2is) in DME treatment using a health insurance claims database. Materials and Methods In this cohort study, we retrospectively analyzed the health insurance claims data of 11 million Japanese individuals from 2005 to 2019. The frequency and duration of TA injection after the initiation of SGLT2is or other antidiabetic drugs were analyzed. Results Among the 2,412 matched patients with DME, the incidence rate of TA injection was 63.8 times per 1,000 person‐years in SGLT2i users and 94.9 times per 1,000 person‐years in non‐users. SGLT2is reduced the risk for the first (P = 0.0024, hazard ratio 0.66, 95% confidence interval 0.50–0.87), second (P = 0.0019, hazard ratio 0.53, 95% confidence interval 0.35–0.80) and third TA (P = 0.0053, hazard ratio 0.44, 95% confidence interval 0.25–0.80) injections. A subanalysis of each baseline characteristic of the patients showed that SGLT2is were effective regardless of the background factors. Conclusions The use of SGLT2is reduced the frequency of TA injection in patients with DME. Therefore, SGLT2i therapy might be a novel, noninvasive and low‐cost adjunctive therapy for DME.

Abstract 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 .

Vertebral hemangiomas are the most common benign lesion of the spine which are often an asymptomatic incidental finding. However, a few hemangiomas are aggressive and characterized by bone expansion and extraosseous extension into the paraspinal and epidural spaces. We report the case of a patient presenting an aggressive vertebral hemangioma causing back pain and bilateral numbness of the legs. Among various treatment modalities, a minimally invasive percutaneous sclerotherapy procedure using ethanolamine oleate under computed tomography and fluoroscopic guidance was safely and successfully performed with good clinical outcomes.

Abstract 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.

Abstract 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.

PurposeTo evaluate the efficacy and safety of transdermal electrical stimulation (TdES) using skin electrodes in patients with central retinal artery occlusion (CRAO).MethodsFive 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.ResultsThe 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.ConclusionIn 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.

Abstract Background The purpose of this study is to determine the epidemiology of tumors of the ocular adnexa and orbit in Japan. Methods We conducted a retrospective study on the histopathological reports in the medical records of the Chiba University Hospital from April 2009 to March 2019. Three hundred and seventy two records were examined. In addition, we examined the annual changes in the major types of tumors including malignant lymphomas and IgG4-related diseases (IgG4-RDs). Results There were 270 conjunctival or eyelid tumors with 166 benign and 104 malignant. There were 102 orbital tumors with 55 benign, 47 malignant tumors, and 21 cases of IgG4-RDs. Ten cases of adenoma (2.7%), another benign tumor, was also diagnosed. The major malignant tumors were malignant lymphoma in 74 cases, sebaceous gland carcinoma (SGC) in 28 cases, basal cell carcinoma in 15 cases, and squamous cell carcinoma in 8 cases. The SGCs were the most common malignant eyelid tumor at 54%. Among the malignant lymphomas, extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue type, MALT lymphomas, was the most common at 51 cases and the second most common was the diffuse large B-cell lymphoma at 11 cases. The ratio of MALT lymphomas to that of all malignant lymphomas increased significantly with years. The serum IgG4 values were measured more often in the last 5 years (70%) than in the former 5 years (33%). Conclusions We conclude that malignant lymphoma is a major malignant tumor in Japan and pathological biopsies should be done proactively to prevent missing IgG4-positive MALT lymphomas.

We report a case of ocular toxoplasmosis that developed a full-thickness macular hole (FTMH) which was successfully treated by pars plana vitrectomy combined with an inverted internal limiting membrane (ILM) flap. A 49-years-old Japanese man was aware of blurred vision in his right eye. Slit-lamp biomicroscopy, ophthalmoscopy, and optical coherence tomography (OCT) of the right eye showed that there was a grayish-white subretinal lesion at the macula accompanied by retinal exudation and mild vitreous flare and iritis. An increase in the level of serum IgM for toxoplasma led to a diagnosis of ocular toxoplasmosis. He developed a FTMH adjacent to the lesion 2 weeks after administering sulfamethoxazole/trimethoprim, and his decimal visual acuity was 0.15. Because the FTMH remained 3 months after the resolution of inflammation and his metamorphopsia persisted, vitrectomy with an inverted ILM flap was performed. After the surgery, the visual acuity improved to 0.2 with the closure of the FTMH confirmed by OCT. A FTMH in an eye with ocular toxoplasmosis was successfully closed by vitrectomy with an inverted ILM flap.

Purpose: The purpose of this report was to present our findings in 4 cases of rhegmatogenous retinal detachment (RRD) that recurred 10, 11, 12, and 17 years after a reattachment surgery by pars plana vitrectomy (PPV). Methods: Four cases of a recurrent RRD had undergone scleral buckling surgery and vitrectomy. Patients: The recurrence of the RRD was observed 10–17 years after the successful attachment by PPV. The macula was detached in all cases, and none of the eyes had severe proliferative vitreoretinopathy. The cause of the recurrence was a new retinal break in 3 eyes and a reopening of an old retinal break in the other eye. The new breaks had a punched-out shape and had neither a horseshoe tear nor an atrophic hole associated with lattice degeneration. PPV combined with scleral buckling was performed, and a reattachment was achieved in all cases. The best-corrected visual acuity (BCVA) at the last visit ranged from 20/30 to 20/25, but the BCVA in 1 eye was 20/200 because of amblyopia. Conclusions: We experienced 4 rare cases of a recurrent retinal detachment 10–17 years after the primary RRD. PPV and scleral buckling were effective and the anatomical and the functional outcomes were good.

Retinitis pigmentosa (RP) is the second leading cause of visual impairment in Japan and causes progressive vision loss in affected patients. Caregiving for patients with RP is associated with socioeconomic impacts; however, data on the magnitude and scope of these impacts are lacking. This cross-sectional study surveyed informal caregivers of patients with RP in Japan. The questionnaire assessed the socioeconomic status of participants; work impacts through the Work Productivity and Activity Impairment Questionnaire adapted for caregivers; and quality of life impacts through the Japanese version of the Caregiver Reaction Assessment (CRA) and the 5-level EQ-5D version (EQ-5D-5L). Of the 37 participating caregivers, 28 (75.7%) were employed. Among those, the average annual income was 2,722,080 yen (n = 20) and the mean loss of work productivity was 6.6%. The mean EQ-5D-5L index score was 0.882, and the mean CRA total score was 2.1. A mild to very severe impact on family life, leisure and hobbies, social life, and mental health was experienced by 83.8%, 78.4%, 75.7%, and 70.3%, respectively. These results suggest that caregivers of patients with RP may be disadvantaged in terms of employment and income and may experience wide-ranging impacts on their quality of daily life.

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.

Abstract We present our findings in an atypical case of ocular syphilis with optic disc neovascularization that was treated with intravitreal bevacizumab and followed by multimodal imaging and electroretinography. A 29-year-old man presented with a chief complaint of night blindness of one-year duration. Our initial examination showed that an optic disc neovascularization was present, and the optical coherence tomographic (OCT) images showed a reduction in the length of the ellipsoid zone of both eyes. Fluorescein angiography showed leakage from the optic disc neovascular tissue, and the presence of nonperfused areas in the peripheral retina. Blood test was strongly positive for syphilis. He was administered oral amoxicillin and prednisolone. He was also treated with an intravitreal injection of bevacizumab which led to a rapid suppression of the neovascularization. However, panretinal photocoagulation had to be performed because OCT angiography and fluorescein angiography detected residual neovascularization. Although these treatments suppressed the activity of the ocular syphilis, electrophysiological improvements were not seen even 1 year after the initial treatment. OCT angiography and electroretinogram are useful techniques for monitoring the effectiveness of the treatments.

We report two cases of chronic rhegmatogenous retinal detachment with a nonperfused peripheral retinal area. Case 1 was an 84-year-old woman who presented with a bullous retinal detachment of the inferior retina and a best-corrected visual acuity of 20/500. A small horseshoe tear was detected in the peripheral superior retina. Fluorescein angiography showed a wide area of nonperfused retina in the inferior retina. The retina was successfully reattached by scleral buckling surgery. Case 2 was a 40-year-old woman who presented with a shallow retinal detachment involving the macula. There were multiple retinal breaks at the pars plana that were secondary to blunt trauma. Fluorescein angiography revealed a wide area of nonperfused retina in the inferior peripheral retina. She underwent scleral buckling surgery, and the retina was successfully reattached. Our findings indicate that clinicians should examine the peripheral retina carefully especially with fluorescein angiography to search for nonperfused areas in eyes with chronic rhegmatogenous retinal detachment.

Abstract Background Evidence-based criteria for the treatment of autoimmune retinopathy (AIR) have not been established. The pathology and clinical features of each antibody causing AIR, and its long-term course are still undetermined. We report our findings in a case of non-paraneoplastic AIR (npAIR) that developed in the fellow eye 10 years after the onset in the first eye. Case presentation Our patient had photophobia in both eyes and a rapidly progressing visual field defect in his right eye at the initial examination. He was diagnosed with non-paraneoplastic AIR based on the clinical findings and immunoblot analyses for anti-retinal antibodies, and he was treated with steroids. Ten years later, a visual field defect developed in the fellow eye, and a diagnosis of npAIR was made. Immunoblot analyses were positive for anti-α-enolase antibodies. He was treated with steroids, immunosuppressants, and plasma exchange. However, the response to the treatment was poor and both eyes eventually became blind. Conclusions As best we know, this is the first case report of npAIR that developed in the fellow eye over 10 years after the development in the first eye. Long-term follow-up and a search for tumor lesions are necessary in cases of npAIR. Further understanding of the long-term course of AIR can contribute to an understanding of the pathology and treatment of npAIR.

Purpose: To report a case in which an internal limiting membrane (ILM) flap that was used to cover an idiopathic macular hole (MH) during pars plana vitrectomy (PPV) with the inverted internal limiting membrane flap technique partially detached from the retina. Most interestingly, the flap fell back spontaneously to re-cover the MH. Observations: A 70-year-old woman presented with a full-thickness MH, and her vision was 20/400. She underwent PPV with an inverted ILM flap and air tamponade. When the intraocular gas was absorbed, the ILM flap detached but was held to the retina where it had not been peeled and the MH was open. Her visual acuity at this time was 20/400. The patient did not want further treatment and was followed by observation alone. At three months after the initial surgery, the ILM flap was noted to have spontaneously re-covered the MH, and her visual acuity improved to 20/200. At 6 months after the re-covering, the flap remained over the MH and the visual acuity remained at 20/200. Conclusions and Importance: Surgeons should be aware that it is possible for an ILM flap created by the inverted ILM flap technique to partially detach from the retina after the tamponade gas is resorbed. Most importantly, the flap can return to re-cover the MH spontaneously.

Purpose. To report a case of persistent fetal vasculature (PFV) with a retinal detachment that worsened after cataract surgery. Pars plana vitrectomy (PPV) was performed which reduced the vitreous traction and reattached the retina. Observations. A 20-year-old Myanmarese woman presented with a mature cataract, and her vision was light perception. She underwent uneventful cataract surgery with implantation of an intraocular lens. Her visual acuity improved to 20/200 immediately after the surgery. However, fibrotic tissue was observed between the optic nerve head and the posterior capsule. She was diagnosed with PFV, and she was followed without any intervention. One and a half years after the cataract surgery, she had an advanced retinal detachment which extended over the inferior two quadrants. Her vision deteriorated to 20/400. She underwent PPV, and the PFV tissue was removed which resulted in the reattachment of the retina. The visual acuity improved to 20/60. Conclusions. Surgeons should be aware that it is possible to worsen a retinal detachment after cataract surgery in the eyes with PFV. A simple technique to release the anterior-posterior traction by the PPV was sufficient to achieve the reattachment of the retina.

The purpose of this study was to compare the efficacies of one initial intravitreal injection of aflibercept followed by a pro re nata (PRN; 1+PRN) regimen to those of three consecutive monthly injections followed by the PRN (3+PRN) regimen for diabetic macular edema (DME) with practical protocols. The medical records of 95 eyes of 71 cases that were diagnosed with DME and had received intravitreal aflibercept (IVA) injections were reviewed. Fifty-seven eyes had received IVA with the 1+PRN regimen, and 38 eyes had received IVA with the 3+PRN regimen. The best-corrected visual acuity (BCVA) and the central macular thickness (CMT) were measured at the baseline and at 1, 3, 6, and 12 months after the IVA. The mean number of injections of the 1+PRN group was 2.9±1.7, which was significantly fewer than that of the 3+PRN group at 4.6±1.4 (P

Purpose. To determine the effects of cataract surgery on contrast visual acuity and retinal sensitivity in patients with retinitis pigmentosa. Methods. Retinal sensitivity and contrast visual acuity were determined by microperimetry (MAIA) and contrast sensitivity acuity tester (CAT-CP), respectively, before and after cataract surgery. The significance of the correlations between visual acuity, retinal sensitivity, contrast visual acuity, improvements after surgery, and macular structure before and after cataract surgery was determined. Results. Retinal sensitivity and contrast visual acuity were significantly improved after cataract surgery. The correlations among postoperative visual acuity, postoperative retinal sensitivities, and preoperative ellipsoid zone length were significant. The postoperative retinal sensitivity of the central 10° and the ellipsoid zone length was particularly significantly correlated. Preoperative contrast visual acuity and the amount of improvement and preoperative retinal sensitivity and the amount of improvement were significantly negatively correlated. The contrast visual acuity under both the 100% and 10% photopic and mesopic conditions improved significantly after cataract surgery. Conclusions. Cataract surgery in retinitis pigmentosa patients with preserved ellipsoid zones significantly improved retinal sensitivity and contrast visual acuity. Cataract surgery can be expected to improve retinal sensitivity and contrast visual acuity under various conditions, even if preoperative visual parameters are low, as long as the ellipsoid zone is preserved.

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.

Purpose: To report two cases with retinitis pigmentosa (RP) who underwent vitreo-retinal surgery and developed severe retinal atrophy. Observations: Case 1 was a 36-year old man who underwent 20-gauge pars plana vitrectomy (PPV) for a macular hole (MH), and Case 2 was a 71-year-old man who also underwent 20-gauge PPV for an epiretinal membrane (ERM). During 13 years follow-up period, severe retinal atrophy developed near the macula that progressed rapidly and the best-corrected visual acuity (BCVA) was reduced to 1.1 logarithm of the minimum angle of resolution (logMAR) units in the MH case and to no light perception in the ERM case. Conclusions and importance: An unexpected severe retinal atrophy can develop long after vitreo-retinal surgery in RP patients.

A 37-year-old Japanese man had his right eye hit by a fist. His right eye developed hypotony maculopathy and secondary cataract, and his visual acuity decreased to 20/200 with an intraocular pressure of 4 mmHg. He underwent phacoemulsification and aspiration, implantation of the intraocular lens, and encircling with a silicone tire. His visual acuity improved to 20/20 and stable for more than one year postoperatively. The intraocular pressure in his right eye increased to 12 mmHg, and maculopathy was resolved entirely. It was suggested that an encircling buckle obstructed the uveoscleral outflow through the cyclodialysis and increased intraocular pressure. Concurrent cataract surgery and encircling was sufficient to improve the vision.

A 61-year-old Japanese woman presented with impairment of her left vision due to macular schisis secondary to branch retinal vein occlusion. Her left vision was 20/50, and schisis was observed inferotemporally. She underwent phacoemulsification and aspiration, implantation of the intraocular lens, and removal of the epiretinal membrane and internal limiting membrane. Her visual acuity stabilized ~20/50 for two and a half years after the initial surgery. However, she developed macula-involving retinal detachment, and her visual acuity declined to counting fingers. She underwent pars plana vitrectomy and removal of the residual vitreous cortex together with the inner retina within the area of vein occlusion. After the removal of silicone oil and the addition of an encircling buckle, the retina remained attached and visual acuity improved to 20/60 at one year after the final surgery. The combination of rhegmatogenous and tractional detachment in the area of schisis was suspected, and vitrectomy with inner retinectomy was effective.

Purpose. Diabetic macular edema (DME) is a vision-threatening condition that develops in diabetic patients. The first-line therapy for DME is intravitreal injections of antivascular endothelial growth factor (anti-VEGF) agents; however, the high frequency of repeat injections, invasiveness of the procedure, and high cost are drawbacks for this treatment. The purpose of this report is to present our findings in 3 patients with chronic DME whose edema was resolved soon after oral doses of sodium-glucose cotransporter-2 (SGLT2) inhibitors were used. Case Presentation. Case 1 was a 66-year-old woman diagnosed with moderate nonproliferative diabetic retinopathy (DR) with DME that had developed a decade earlier. The DME persisted for 4 years in the left eye. The addition of oral empagliflozin, a SGLT2 inhibitor, led to a marked improvement of the DME after one month, and this improvement continued over two years. Case 2 was a 68-year-old woman who was diagnosed with preproliferative DR with bilateral DME. The addition of oral dapagliflozin led to the improvement of the DME after two months, and this improvement continued over one year. Case 3 was a 61-year-old woman who was diagnosed with moderate nonproliferative DR with DME. Oral luseogliflozin was given which led to better glycemic control, and her left central retinal thickness (CRT) was markedly reduced after only two weeks. This reduction was maintained in her left eye for six months without any additional ophthalmic procedures. Conclusions. Although this study involved only three cases, our findings indicate that SGLT2 inhibitors might have possible efficacy for chronic DME.

Purpose. To investigate the outcomes of pars plana vitrectomy (PPV) combined with scleral buckling (SB) in treating eyes with an early recurrent rhegmatogenous retinal detachment (rRRD). Methods. This was a retrospective, interventional case series of 21 eyes with an early rRRD treated by PPV combined with SB. The significance of the associations between the variants before the surgeries and the final best-corrected visual acuity (BCVA) was determined. Results. The average age of the patients was 61.0 ± 9.6 years. A retinal reattachment was observed in 20 of 21 eyes (95.2%) after a single reoperation. The BCVA was 0.91 ± 0.90 logMAR units before the initial surgery and 0.94 ± 0.94 logMAR units before the reoperations, and it improved significantly to 0.49 ± 0.50 logMAR units after the reoperation (P = 0.016, P = 0.002, respectively). The preoperative BCVA was significantly correlated with the final BCVA (P = 0.043, r = 0.445 before the primary surgery; P

Abstract Background To present our findings in a case of convulsive seizures and loss of consciousness that developed during recording electroretinograms (ERG). Case presentation A 34-year-old man had reduced vision in his left eye for about 15 years, and night blindness for about two years. His visual acuity was 20/15 in the right eye and 20/50 in the left eye. The fundus was normal but the sensitivity in the macular region of the left eye was decreased. Optical coherence tomography (OCT) showed partial loss of the interdigitation zone. Upon completion of the flicker ERG recording, a paralysis developed in both upper limbs, then convulsions of the lower limbs followed by a loss of consciousness. The convulsions disappeared after an intravenous injection of diazepam. After that incident, he reported that he had had previous conscious-loss seizures. Conclusions Photosensitive epileptic seizures can occur with the light stimuli used for conventional ERG recordings. We recommended that clinicians request information on any prior seizure episodes of the patients and their family members before ERG recordings.

Quantitative and qualitative evaluation of synapses is crucial to understand neural connectivity. This is particularly relevant now, in view of the recent advances in regenerative biology and medicine. There is an urgent need to evaluate synapses to access the extent and functionality of reconstructed neural network. Most of the currently used synapse evaluation methods provide only all-or-none assessments. However, very often synapses appear in a wide spectrum of transient states such as during synaptogenesis or neural degeneration. Robust evaluation of synapse quantity and quality is therefore highly sought after. In this paper we introduce QUANTOS, a new method that can evaluate the number, likelihood, and maturity of photoreceptor ribbon synapses based on graphical properties of immunohistochemistry images. QUANTOS is composed of ImageJ Fiji macros, and R scripts which are both open-source and free software. We used QUANTOS to evaluate synaptogenesis in developing and degenerating retinas, as well as de novo synaptogenesis of mouse iPSC-retinas after transplantation to a retinal degeneration mouse model. Our analysis shows that while mouse iPSC-retinas are largely incapable of forming synapses in vitro, they can form extensive synapses following transplantation. The de novo synapses detected after transplantation seem to be in an intermediate state between mature and immature compared to wildtype retina. Furthermore, using QUANTOS we tested whether environmental light can affect photoreceptor synaptogenesis. We found that the onset of synaptogenesis was earlier under cyclic light (LD) condition when compared to constant dark (DD), resulting in more synapses at earlier developmental stages. The effect of light was also supported by micro electroretinography showing larger responses under LD condition. The number of synapses was also increased after transplantation of mouse iPSC-retinas to rd1 mice under LD condition. Our new probabilistic assessment of synapses may prove to be a valuable tool to gain critical insights into neural-network reconstruction and help develop treatments for neurodegenerative disorders.

Macular hole has been believed to be a disorder of vitreomacular interface, which forms as a result of abnormal vitreous traction from incomplete vitreous detachment. However, our recent studies demonstrated that dynamic forces, caused by mobile posterior cortical vitreous with fluid currents, exist already at early stages of macular hole development. Therefore, in eyes with flexible vitreous, the contributions of tractional forces due to vitreous shrinkage are unlikely. These facts indicate that in the development of idiopathic macular holes, there is a greater contribution of dynamic forces than has been previously reported. This review also evaluates the recent findings in the assessment of the idiopathic macular holes and the recent therapeutic strategies for optimal management. Inner limiting membrane is considered to improve anatomical closure rate; however, it is still questionable if peeling is necessary in holes less than 250 µm. There are plenty of publications indicating that in the management of small and medium size hole (less than 400 µm), use of long-lasting gas and face-down position is not always required; however, it may be necessary for the treatment of large holes. Ocriplasmin and expansile gas had been reported to be successful for management of small- and medium-sized holes and vitreomacular attachment.

A 17-year-old male presented with acute bilateral paracentral scotomata and blurred vision. Funduscopic examination showed bilateral macular serous retinal detachment and yellow-white placoid lesions at the level of retinal pigment epithelium. OCT study showed typical VKH disease findings with marked choroidal thickening and macular serous retinal detachment partly with subretinal septa in both eyes. FA demonstrated hypofluorescence at the placoid lesions in the early phase and hyperfluorescence in the late phase. Laboratory investigation showed negative result for HLA-DR4 serotype and the patient’s cerebrospinal fluid test values were within normal range. We made the diagnosis of APMPPE from these results. At 2-month follow-up without the use of corticosteroids, OCT reexamination showed complete amelioration of subretinal fluid in both eyes. Patchy pigmentary lesions also resolved clinically with partial chorioretinal scars. The results in this case suggested OCT findings in APMPPE patients could be similar to characteristic features usually found in acute VKH disease. We recommend comprehensive assessments such as FA, cerebral spinal fluid analysis, and HLA typing which help in leading proper diagnosis.

Purpose. To compare the visual and surgical outcomes after a reuse or a replacement of a dislocated in-the-bag intraocular lens (IOL). Methods. This was a retrospective, nonrandomized case series at a single ophthalmological institution. Cases with an in-the-bag dislocation of an IOL were treated by pars plana vitrectomy and the reuse or the replacement of the IOL. The lens was held by intrascleral fixation of the haptics of the IOL under both conditions. The same dislocated IOL was reused in 6 eyes (group A) or it was replaced with another IOL in the other 9 eyes (group B). The pre- and postoperative parameters analyzed included the visual acuity, refractive error, corneal endothelial cell density, and intraocular pressure (IOP). Results. There was no significant difference between the two groups in the postoperative visual acuity (P=0.388), refractive error (P=0.955), IOP (P=0.529), and endothelial cell loss (P=0.940). A breakage or a tilting of the IOL was observed and required replacement in three eyes in the reuse group (P=0.044). Conclusions. Half of the cases with reused in-the-bag dislocated IOL had a breakage or a tilting of the IOL. The replacement of the in-the-bag dislocated IOL is better than the reuse of the IOL with intrascleral haptics fixation.

Conjunctival amyloidosis is a very rare disease, and its presence may be a sign of systemic amyloidosis. We present our ocular and systemic findings in a patient with conjunctival amyloidosis. A 43-year-old man had repeated subconjunctival hemorrhages (SCHs) for two years and was referred to the Chiba University Hospital. He had comprehensive ophthalmological and systemic examinations to determine the cause of the SCHs. His visual acuities were 1.2 OU, and the intraocular pressures were 13-14 mmHg OU. Magnetic resonance imaging was normal. Initially, the SCH was the only abnormality. After 3 months, the SCH had partially cleared, and a pink mass was detected in the superior area of the subconjunctiva. Partial biopsy and histopathological examinations showed a greenish birefringence and dichroism under polarized light illumination. The birefringence was located in amyloid fibers. Immunofixation electrophoresis detected λ-light chain abnormality in the ocular biopsy specimen but systemic examinations did not find any lesions. Multiple myeloma was ruled out, and the patient is being followed closely to detect any early signs of systemic amyloidosis. Because repeated SCHs might be initial signs of systemic amyloidosis, patients with conjunctival amyloidosis should be comprehensively examined for systemic amyloidosis because of its poor life prognosis.

Sterols are widely distributed in nature from lipids in organisms to sediments. As a conventional method, extraction and derivatization with TMS have been applied for sterol analysis, requiring a long preparation time for gas chromatography−mass spectrometry analysis. In this study, for sterol analysis, thermochemolysis using tetramethylammonium hydroxide (TMAH) was applied. This method performs hydrolysis and methylation simultaneously; thus, free and ether-bonding sterols can be analyzed as sterol methyl ethers in a relatively short time period. A sediment sample from a tideland (the Yatsu tideland, Japan) was analyzed using the TMAH method, and we detected more than 10 sterols, which include cholest-5-en-3β-ol (cholesterol), 24-ethylcholest-5-en-3β-ol (sitosterol), 24-methylcholesta-5,22E-3β-ol (brassicasterol), 24-ethylcholesta-5,24(28)Z-dien-3β-ol (isofucosterol), 4α,23,24-trimethyl-5α(H)-cholest-22E-en-3β- ol (dinosterol), and 5β(H)-cholestan-3β-ol (coprostanol). The detection of the various sterols can be attributed to multiple natural and artificial sources around the Yatsu tideland. In this paper, the mass spectra of these sterols are provided together with an interpretation of their fragmentation patterns. Additionally, the fecal pollution in the Yatsu tideland is discussed in the context of the detection of coprostanol.

An 87-year-old Japanese man presented with retinal angiomatous proliferation (RAP) and a retinal pigment epithelium (RPE) detachment in his right eye. His decimal best-corrected visual acuity was 0.15 in the right eye, and optical coherence tomography (OCT) showed a vitreomacular adhesion in the right eye as well. After 3 monthly intravitreal injections of ranibizumab, the size and height of the RPE detachment was significantly reduced. The accumulated intra- and subretinal fluid also disappeared, but the vitreomacular traction remained. Pars plana vitrectomy was performed, and the posterior hyaloid was separated from the retina with a vitrectomy cutter without any intraoperative complications. Two months after the surgery, a large RPE tear was observed over the macular area. His visual acuity decreased to 0.06 and remained unchanged thereafter. We suggest that the small tear led to the larger RPE tear because vitreomacular traction was transmitted to the RPE through the fibrovascular tissue of the RAP during the creation of the hyaloid detachment. Because such an RPE tear has not been reported after vitrectomy for vitreomacular traction, surgeons need to pay special attention to this potential complication in eyes with vitreomacular traction and RAP.

Aims and Objectives: Ethanol is widely used for the embolization treatment of vascular malformations, but it can also cause serious complications such us pulmonary hypertension, cardiopulmonary collapse and death. The complications are considered secondary to pulmonary vasospasm and ethanol-induced sludge embolism, etc., We studied the hemodynamic effects of intravenous absolute ethanol injection and ethanol sludge injection in pigs. Materials and Methods: A total of 5 pigs underwent intravenous injection of ex vivo generated ethanol-induced sludge in which residual ethanol was removed (Group S) and 4 pigs underwent intravenous injection of absolute ethanol (Group E). Hemodynamic parameters related to the pulmonary and systemic circulation were compared between the groups. Results: Transient pulmonary hypertension was observed in both groups and the hemodynamic changes were similar in both groups. Conclusions: Sludge can induce transient pulmonary hypertension or cardiopulmonary collapse, without ethanol and may be the mechanism by which ethanol induces its adverse hemodynamic effects.

Aims: Isopropyl unoprostone (IU), a maxi-K channel activator, is used topically to treat glaucoma, and has been reported to have neuroprotective effects on retinal neurons in vitro and in vivo. The purpose of this non-comparative pilot study was to determine whether topical IU will alter the sensitivity of the central retina in patients with retinitis pigmentosa (RP). Settings and Design : Non-comparative pilot study. Materials and Methods : IU was given topically twice a day for 6 months to both eyes of 30 patients with typical RP. The visual acuity was measured with a Japanese Snellen chart, and the mean retinal sensitivities were obtained by fundus-related microperimetry (MP-1). The mean deviation (MD) of the visual field was determined with a Humphrey field analyzer (HFA). All measurements were made before and 6 months after the treatment. Statistical Analysis Used : Wilcoxon and the Mann-Whitney U tests (SPSS, SPSS Inc., Chicago, IL). Results: After the treatment, the mean retinal sensitivity within the central 2° and 10° improved significantly from 12.3 ± 4.8 dB to 14.7 ± 5.5 dB (P = 0.001) and from 9.1 ± 5.4 dB to 11.0 ± 6.2 dB (P = 0.001), respectively. Conclusions: These short-term results suggest topical IU can improve the central retinal sensitivity in RP patients. It will be necessary to examine longer treatment periods in a controlled study to determine the effectiveness of topical IU in RP patients.

Previous studies of neuromyelitis optica spectrum disorder (NMOSD) using spectral domain optical coherence tomography (SD-OCT) showed that the outer nuclear layer (ONL) in eyes without a history of optic neuritis (ON) was thinner than that of healthy controls. It remains unclear whether the ONL thinning is caused by a direct attack on the retina by an autoantibody or a retrograde degeneration.To determine the mechanisms involved in the retinal damage in eyes with NMOSD without ON.SD-OCT was used to determine the thicknesses of the different retinal layers of 21 eyes of 12 NMOSD patients without prior ON and 19 eyes of 10 healthy controls. Eyes with peripapillary retinal nerve fiber layer (RNFL) thinning were excluded to eliminate the confounding effects of retrograde degeneration. Microperimetry was used to determine the central retinal sensitivity. The data of the two groups were compared using generalized estimated equation models to account for inter-eye dependencies.The ganglion cell plus inner plexiform layer and the inner nuclear layer plus outer plexiform layer thicknesses of the NMOSD eyes were not significantly different from that of the control eyes (P = 0.28, P = 0.78). However, the ONL and average macular thickness (AMT) in the NMOSD eyes were significantly thinner than that of the control eyes (P = 0.022, P = 0.036). The retinal sensitivity in the central 10°, 10° to 2°, and 2° sectors were significantly lower in the NMOSD eyes than in the control eyes (P = 0.013, P = 0.022, P = 0.002).The ONL thinning, AMT thinning, and reduced retinal sensitivity in eyes with NMOSD without significant peripapillary RNFL thinning are most likely due to direct retinal pathology.

A 75-year-old Japanese woman presented with a juxtapapillary retinal capillary hemangioma (RCH) in her left eye. Twelve months after the initial examination, the size of the hemangioma had increased and the exudation from the RCH involved the macula. Her best-corrected visual acuity (BCVA) had decreased from 0.8 to 0.3. A total of five intravitreal injections of bevacizumab (IVB; 1.25 mg) was given but the RCH did not respond. A photodynamic therapy (PDT) was done using multiple laser spots to avoid damaging the optic nerve head. After the first PDT, the subfoveal fluid was reduced but not completely gone. One week after the second PDT, a massive subretinal hemorrhage developed. The subretinal hemorrhage was successfully displaced by injecting intraocular sulfur hexafluoride (SF6) gas. At the 3-year follow-up examination, no subretinal hemorrhage or fluid was observed at the macula and the BCVA remained at 0.05. Our case was resistant to the combination of anti-vascular endothelial growth factor (VEGF) and PDT and had a rare massive subretinal hemorrhage. A further collection of RCH cases treated with anti-VEGF and PDT that would justify this treatment is necessary.

Natsuyo Hata1, Toshiyuki Oshitari1,2, Akiko Yokoyama1,3, Yoshinori Mitamura1, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan; 2Department of Ophthalmology, Kimitsu Central Hospital, Kisarazu City, Chiba, Japan; 3Department of Ophthalmology, Inoue Memorial Hospital, Chuo-ku, Chiba, JapanAbstract: The purpose of this study was to determine whether the expression of ER stress-related factors IRE1α, apoptosis signal-regulating kinase 1 (ASK1), SAPK/ERK kinase 1 (SEK1) and c-Jun N-terminal kinase (JNK) is associated with the damaged retinal neurons induced by ischemia-reperfusion injury. After 60 minutes of ischemia, the rat retinas were reperfused, and retinas were isolated and fixed after 6, 9, 12, 18, and 24 hours, and 2, 5, and 9 days of reperfusion. Cryosections were immunostained with Fluoro-Jade B, a degenerating neuron marker to label degenerating neurons. Semi-quantitative analysis of the expression of IRE1α, ASK1, SEK1, and JNK were performed in both control and ischemic retinas. In ischemic retinas, the intensities of IRE1α immunoreactivity in the ganglion cell layer (GCL) were significantly higher than in the control retinas. In ischemic retinas, the numbers of SEK1-, ASK1-, and JNK-positive cells were significantly increased in the GCL compared to those in the control retinas. In addition, the cells that were positive for SEK1-, ASK1-, and JNK were also positive for Fluoro-Jade B-positive cells. These results indicate that the increased expression of ER stress-related factors was, in part, associated with the retinal neuronal abnormalities after ischemia-reperfusion injury in rat retinas.Keywords: endoplasmic reticulum, IRE1α, apoptosis signal-regulating kinase 1, SAPK/ERK kinase 1, c-Jun N-terminal kinase, Fluoro-Jade B, ischemia-reperfusion injury

Toshiyuki Oshitari1,2, Natsuyo Hata1, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba City, Chiba, Japan; 2Department of Ophthalmology, Kimitsu Central Hospital, Kisarazu City, Chiba, JapanAbstract: Endoplasmic reticulum (ER) stress is involved in the pathogenesis of several diseases including Alzheimer disease and Parkinson disease. Many recent studies have shown that ER stress is related to the pathogenesis of diabetes mellitus, and with the death of pancreatic β-cells, insulin resistance, and the death of the vascular cells in the retina. Diabetic retinopathy is a major complication of diabetes and results in death of both neural and vascular cells. Because the death of the neurons directly affects visual function, the precise mechanism causing the death of neurons in early diabetic retinopathy must be determined. The ideal therapy for preventing the onset and the progression of diabetic retinopathy would be to treat the factors involved with both the vascular and neuronal abnormalities in diabetic retinopathy. In this review, we present evidence that ER stress is involved in the death of both retinal neurons and vascular cells in diabetic eyes, and thus reducing or blocking ER stress may be a potential therapy for preventing the onset and the progression of diabetic retinopathy.Keywords: endoplasmic reticulum stress, diabetic retinopathy, vascular cell death, neuronal cell death

The purpose of this study is to identify the risk factors for a recurrence or persistence of diabetic macular oedema (DME) after a sub-Tenon’s capsule triamcinolone acetonide (STTA) injection. The medical records of 124 patients (124 eyes) treated by STTA were reviewed. The age, sex, HbA1c level, best-corrected visual acuity, central macular thickness, insulin use, pioglitazone use, systemic hypertension, serous retinal detachment, proteinuria, panretinal photocoagulation, microaneurysm photocoagulation (MAPC), subthreshold micropulse diode laser photocoagulation (SMDLP), cataract surgery, and history of vitrectomy were examined by logistic regression analysis. Procedures of MAPC and SMDLP were significantly associated with DME treated with STTA (P=0.0315, P=0.04, resp.). However, a history of vitrectomy was found to have significantly fewer recurrences or persistent DME after STTA (P=0.0464). In conclusion, patients who required combined MAPC or SMDLP with a STTA injection had significantly higher refractoriness to STTA, but postvitrectomy may prevent the recurrence or persistence of DME after STTA injection.

To determine the effect of advanced glycation end-products (AGEs) on neurite regeneration, and also to determine the regenerative effects of different neurotrophic factors (NTFs) on rat retinal explants, the retinas of SD rats were cultured in three-dimensional collagen gels and incubated in 6 types of media: (1) serum-free control culture media; (2) 100 μg/mL AGEs-BSA media; (3) AGEs-BSA + 100 ng/mL neurotrophin-4 (NT-4) media; (4) AGEs-BSA + 100 ng/mL hepatocyte growth factor media; (5) AGEs-BSA + 100 ng/mL glial cell line-derived neurotrophic factor media; or (6) AGEs-BSA + 100 µM tauroursodeoxycholic acid media. After 7 days, the number of regenerating neurites was counted. The explants were immunostained for nuclear factor-κB (NF-κB) and specificity protein 1 (SP1). Statistical analyses were performed by one-way ANOVA. In retinas incubated with AGEs, the numbers of neurites were fewer than in control. All of the NTFs increased the number of neurites, and the increase was more significant in the NT-4 group. The number of NF-κB and SP1 immunopositive cells was higher in retinas exposed to AGEs than in control. All of the NTFs decreased the number of NF-κB immunopositive cells but did not significantly affect SP1 expression. These results demonstrate the potential of the NTFs as axoprotectants in AGEs exposed retinal neurons.

To determine anti-allergic effects of Koboku, a Chinese herbal medicine, we investigated its inhibitory action on the production of cysteinyl leukotrienes (LT) and LTB4, which are important chemical mediators in the pathogenesis of allergic diseases. A231 87-stimulated synthesis of cysteinyl LT and LTB4 was measured by HPLC in the absence or presence of various concentrations of Koboku in rat basophilic leukemia-1 (RBL-1) cells. In a dose-dependent manner, Koboku inhibited synthesis of cysteinyl LT and LTB4 by up to 92.3 and 100%, respectively. Immunoglobulin E-mediated release of cysteinyl LT and LTB4, which was measured by specific radioimmunoassay (RIA) was also inhibited by Koboku in RBL-2H3 cells. Sites of inhibition of Koboku in the metabolic pathway of LT synthesis were phospholipase A2 (PLA2) and 5-lipoxygenase (5-LO), but not LTC4 synthase or LTA4 hydrolase. We conclude that the anti-allergic effect of Koboku may be attributable, at least in part, to the inhibition of LT synthesis.

Archaeal 16S rRNA gene compositions and environmental factors of four distinct solfataric acidic hot springs in Kirishima, Japan were compared. The four ponds were selected by differences of temperature and total dissolved elemental concentration as follows: (1) Pond-A: 93°C and 1679 mg L−1, (2) Pond-B: 66°C and 2248 mg L−1, (3) Pond-C: 88°C and 198 mg L−1, and (4) Pond-D: 67°C and 340 mg L−1. In total, 431 clones of 16S rRNA gene were classified into 26 phylotypes. In Pond-B, the archaeal diversity was the highest among the four, and the members of the order Sulfolobales were dominant. The Pond-D also showed relatively high diversity, and the most frequent group was uncultured thermoacidic spring clone group. In contrast to Pond-B and Pond-D, much less diverse archaeal clones were detected in Pond-A and Pond-C showing higher temperatures. However, dominant groups in these ponds were also different from each other. The members of the order Sulfolobales shared 89% of total clones in Pond-A, and the uncultured crenarchaeal groups shared 99% of total Pond-C clones. Therefore, species compositions and biodiversity were clearly different among the ponds showing different temperatures and dissolved elemental concentrations.

The purpose of this study is to describe the 26-year-old patient with developed macular hole after bilateral laser in situ keratomileusis (LASIK). A macular hole with sharp margins and irregular surface of surrounding retina appeared in the left eye of the female 26-year-old patient two months after LASIK for correction of myopia (followup of 6 months). Although the best corrected visual acuity (BCVA) after LASIK was 1.0, after the macular hole has developed BCVA became 0.5. After surgery, the final visual acuity recovered to 0.7. Macular hole may develop after LASIK for myopia correction due to unknown changes of vitreoretinal interface. Complete informed consent must be obtained from patients with high myopic eyes before LASIK.

With recent development of spectral-domain optical coherence tomography (SD-OCT), the pathological changes of retina can be observed in much greater detail. SD-OCT clearly delineates three highly reflective lines in the outer retina, which are external limiting membrane (ELM), photoreceptor inner and outer segment (IS/OS) junction, and cone outer segment tips (COST) in order from inside. These lines can serve as hallmarks for the evaluation of photoreceptor condition. In retinitis pigmentosa (RP) leading to photoreceptor degeneration, the ELM, IS/OS, and COST lines are shortened with the progression of the disease. In addition, shortening of the ELM, IS/OS and COST lines is significantly associated with each other. The line length is longest in the ELM, followed by the IS/OS, and COST, suggesting that retinal layer becomes disorganized first at the COST, followed by the IS/OS and finally the ELM. This finding is consistent with the previous report that the earliest histopathological change in RP is a shortening of the photoreceptor outer segments. On the other hand, retinal layer becomes restored first at the ELM, followed by the IS/OS and finally the COST after macular hole surgery. There may be a directionality of photoreceptor impairment or restoration on optical coherence tomographic image.

We present our findings in a case of primary neuroendocrine carcinoma (NEC) of the lacrimal gland and a case of primary Merkel cell carcinoma (MCC) of the eyelid. An 86-year-old man noticed a swelling of the left upper eyelid three months earlier. We performed excision biopsy and histopathological examination indicated that he had a primary NEC of the left lacrimal gland. He underwent chemotherapy followed by excision including the clinically visible margins and 50 Gy radiotherapy of the surgical margins. He had neither recurrence nor metastasis for 6 months since the last radiotherapy. An 80-year-old man noticed a nodule in the right upper eyelid and was referred to our hospital because the size was increasing rapidly. A complete surgical excision of the margins of the tumor was performed with histopathological confirmation of negative margins. The final diagnosis was a primary MCC of the right upper eyelid. After surgery, he underwent 50 Gy radiotherapy on the neck to prevent metastasis. No recurrence or metastasis was found for two years. Although primary NEC of the ocular adnexa is extremely rare, the tumor has high malignancy and readily metastasizes. Thus, combined therapy including surgery, radiotherapy, and/or chemotherapy is needed for complete management of NEC.

A 52-year-old Japanese woman presented with optical symptoms, including left-sided myodesopsia, blurred vision, narrowed visual field, and diminished visual acuity. Ocular evaluation revealed a metastatic tumor in the choroid. Further examinations identified pulmonary adenocarcinoma as the primary tumor. Because an epidermal growth factor receptor gene (EGFR) mutation was detected in a biopsy specimen, gefitinib treatment was initiated. Dramatic responses were obtained in the primary tumor and metastatic foci. Optical symptoms improved and remained stable for 5 months during the treatment, until relapse. This report demonstrates that gefitinib is effective for choroidal metastasis of pulmonary adenocarcinoma harboring an EGFR mutation.

Purpose. To determine the factors associated with the development of a macular hole (MH) after successful rhegmatogenous retinal detachment (RRD) surgery. Methods. Of 1260 eyes that underwent surgery for RRD between April 2005 and March 2010 in our hospital, the medical records of 4 cases from our hospital and one case from another hospital that had undergone RRD surgery and later developed MH were reviewed. This is a retrospective study. Results. 837 eyes underwent pars plana vitrectomy (PPV) with or without scleral buckling (SB), and 423 eyes underwent SB. The four cases that developed MH had PPV alone and one case had PPV with SB. After including the results of three earlier reports, the mean interval for the MH to develop after SB alone was significantly shorter than after PPV alone or after PPV with SB. Conclusions. The SB procedures might accelerate the development of MH after RRD surgery.

Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease including autosomal recessive (ar), autosomal dominant (ad), and X-linked inheritance. Recently, arRP has been associated with mutations in EYS (Eyes shut homolog), which is a major causative gene for this disease. This study was conducted to determine the spectrum and frequency of EYS mutations in 100 Japanese arRP patients. To determine the prevalence of EYS mutations, all EYS exons were screened for mutations by polymerase chain reaction amplification, and sequence analysis was performed. We detected 67 sequence alterations in EYS, of which 21 were novel. Of these, 7 were very likely pathogenic mutations, 6 were possible pathogenic mutations, and 54 were predicted non-pathogenic sequence alterations. The minimum observed prevalence of distinct EYS mutations in our study was 18% (18/100, comprising 9 patients with 2 very likely pathogenic mutations and the remaining 9 with only one such mutation). Among these mutations, 2 novel truncating mutations, c.4957_4958insA (p.S1653KfsX2) and c.8868C>A (p.Y2956X), were identified in 16 patients and accounted for 57.1% (20/35 alleles) of the mutated alleles. Although these 2 truncating mutations were not detected in Japanese patients with adRP or Leber's congenital amaurosis, we detected them in Korean arRP patients. Similar to Japanese arRP results, the c.4957_4958insA mutation was more frequently detected than the c.8868C>A mutation. The 18% estimated prevalence of very likely pathogenic mutations in our study suggests a major involvement of EYS in the pathogenesis of arRP in the Japanese population. Mutation spectrum of EYS in 100 Japanese patients, including 13 distinct very likely and possible pathogenic mutations, was largely different from the previously reported spectrum in patients from non-Asian populations. Screening for c.4957_4958insA and c.8868C>A mutations in the EYS gene may therefore be very effective for the genetic testing and counseling of RP patients in Japan.

Although multicentric Castleman disease is a rare but life-threatening disease, eye complications are extremely uncommon. We present a case of refractory uveitis accompanied with Castleman disease successfully treated with tocilizumab. A 58-year-old man with Castleman disease was introduced for refractory uveitis to Chiba University Hospital. Large cells were detected in the anterior chamber and increased vascular permeability of retinal vessels has been found in both eyes. Although the patient was treated with oral and eye drop steroid treatment, the uveitis symptoms had not decreased. The serum levels of CRP and IL-6 were increased. The level of IL-6 concentration in the anterior chamber was the same as the serum level of IL-6. The humanized anti-IL-6 receptor-antibody (tocilizumab) was administrated for the patient because of poor general condition. After tocilizumab treatment, large cells in the anterior chamber were undetectable and vascular permeability was improved in FA. The serum levels of CRP and IL-6 decreased and the general condition improved. The side effect of tocilizumab was not observed during the treatment. Tocilizumab treatment was significantly effective for uveitis accompanied with Castleman disease. Although it is extremely rare, uveitis accompanied with Castleman disease may be one of the hallmarks to consider tocilizumab treatment.