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Purpose: Anti-vascular endothelial growth factor (VEGF) therapy is the most prevalent intervention for exudative lesions secondary to neovascular age-related macular degeneration (nAMD) and other macular neovascularization (MNV). However, in some cases refractory to the latest anti-VEGF agents is associated with epiretinal membrane (ERM) or vitreomacular traction. We applied a vitrectomy to remove those pathologies which may be effective for reducing the exudation. Observations: In this case report, we present 2 cases with sustained subretinal fluid and macular neovascularization secondary to nAMD or dome-shaped macula that poorly responded to anti-VEGF therapy. In both cases, removing thin ERM or vitreomacular traction with an inner limiting membrane peeling promptly resolved the subretinal fluid and no recurrence was observed thereafter. Conclusions and importance: Vitrectomy could be an effective modality for anti-VEGF drug-resistant MNV cases with vitreomacular traction or ERM even in the anti-VEGF era.

Abstract Introduction The EVEREST II study previously reported that intravitreally administered ranibizumab (IVR) combined with photodynamic therapy (PDT) achieved superior visual gain and polypoidal lesion closure compared to IVR alone in patients with polypoidal choroidal vasculopathy (PCV). This follow-up study reports the long-term outcomes 6 years after initiation of the EVEREST II study. Methods This is a non-interventional cohort study of 90 patients with PCV from 16 international trial sites who originally completed the EVEREST II study. The long-term outcomes were assessed during a recall visit at about 6 years from commencement of EVEREST II. Results The monotherapy and combination groups contained 41 and 49 participants, respectively. The change in best-corrected visual acuity (BCVA) from baseline to year 6 was not different between the monotherapy and combination groups; − 7.4 ± 23.0 versus − 6.1 ± 22.4 letters, respectively. The combination group had greater central subfield thickness (CST) reduction compared to the monotherapy group at year 6 (− 179.9 vs − 74.2 µm, p = 0.011). Fewer eyes had subretinal fluid (SRF)/intraretinal fluid (IRF) in the combination versus monotherapy group at year 6 (35.4% vs 57.5%, p = 0.032). Factors associated with BCVA at year 6 include BCVA (year 2), CST (year 2), presence of SRF/IRF at year 2, and number of anti-VEGF treatments (years 2–6). Factors associated with presence of SRF/IRF at year 6 include combination arm (OR 0.45, p = 0.033), BCVA (year 2) (OR 1.53, p = 0.046), and presence of SRF/IRF (year 2) (OR 2.59, p = 0.042). Conclusion At 6 years following the EVEREST II study, one-third of participants still maintained good vision. As most participants continued to require treatment after exiting the initial trial, ongoing monitoring and re-treatment regardless of polypoidal lesion status are necessary in PCV. Trial Registration ClinicalTrials.gov identifier, NCT01846273.

Introduction: Ocular metastases from breast cancer, particularly involving the optic nerve, are rare and pose a diagnostic challenge. Typically, optic nerve metastases are believed to originate from nearby choroidal metastases or hematogenous spread through the posterior ciliary arteries. However, there have been some reports of metastases through leptomeningeal dissemination. The aim of this report was to describe a case of multiple brain metastases from breast cancer without subjective symptoms other than central scotoma, which was diagnosed with repeated magnetic resonance imaging (MRI). Case Presentation: A 62-year-old woman who had previously undergone a mastectomy for left breast cancer complained of left ocular pain during eye movement and left visual loss. Initial contrast-enhanced MRI showed no significant abnormalities, and idiopathic optic neuritis was suspected. Despite steroid pulse therapy, her visual function did not improve. After four and a half months, her visual acuity worsened, and repeat contrast-enhanced MRI showed brain metastases involving the optic nerve sheath. Conclusion: Despite the multiple brain metastases, ultimately the patient’s only symptom was unilateral visual loss. These findings highlight the usefulness of repeated contrast-enhanced MRI for detecting brain metastases, especially in cases without other apparent neurological symptoms or initial imaging abnormalities.

Abstract To investigate whether aldosterone (ALD) and hydrocortisone (HC) change the gene expression of SLC7A5, which encodes the large neutral amino acid transporter small subunit 1 (LAT1), and the transport activity of LAT1 in the retinal pigment epithelium (RPE) in vitro. ARPE-19 cells were grown to confluence. After withdrawing the serum, ALD or HC was added with several doses and incubated, and SLC7A5 gene expression was measured. The influx and efflux transport of sodium fluorescein (Na-F) were evaluated using the Transwell culture system. SLC7A5 gene expression was upregulated by ALD and downregulated by HC in a dose-dependent manner. Both ALD and HC significantly increased the influx and efflux Na-F transport of RPE cells at a dose that did not change the expression of SLC7A5. JPH203, a specific inhibitor of LAT1, significantly reduced accelerated Na-F transport. Both ALD and HC increased the gene expression of zonula occludin-1 (ZO-1) although they did not change the immunoreactivity of ZO-1 in RPE cells. LAT1 may play an important role in increasing Na-F transport associated with ALD and HC administration. A specific LAT1 inhibitor may effectively regulate the increased material transport of RPE induced by ALD and HC.

PurposeTo examine the molecular biological differences between conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma and orbital MALT lymphoma in ocular adnexa lymphoma.MethodsObservational case series. A total of 129 consecutive, randomized cases of ocular adnexa MALT lymphoma diagnosed histopathologically between 2008 and 2020.Total RNA was extracted from formalin-fixed paraffin-embedded tissue from ocular adnexa MALT lymphoma, and RNA-sequencing was performed. Orbital MALT lymphoma gene expression was compared with that of conjunctival MALT lymphoma. Gene set (GS) analysis detecting for gene set cluster was performed in RNA-sequence. Related proteins were further examined by immunohistochemical staining. In addition, artificial segmentation image used to count stromal area in HE images.ResultsGS analysis showed differences in expression in 29 GS types in primary orbital MALT lymphoma (N=5,5, FDR q-value 1) independent of age and sex on multivariate analysis (P=0.004). Stroma area in tumor were significant difference(P

PurposeTo investigate relationship between vitreous interleukin-6 levels and vitreous particles findings on widefield optical coherence tomography in posterior uveitis.MethodsThis retrospective study examined vitreous inflammatory cells (hyperreflective particles) of posterior uveitis on widefield optical coherence tomography (WOCT). We examined the number of hyperreflective particles (possibility of vitreous inflammatory cells) observed on WOCT and the correlations with interleukin-6 (IL-6) levels. The relationship between vitreous IL-6 levels and image findings from WOCT from 37 eyes (34 patients) with posterior uveitis were analyzed. Mean patient age was 63.4±15.7 years. (Mean± standard deviation) IL-6 concentration in vitreous humor was 79.9±7380.9 pg/mL Uveitis was infectious in 9 cases and non-infectious in 28 cases with multiplex polymerase chain reaction system. We measured the number and size of vitreous cells in the posterior vitreous, defined as the space between the upper vitreous and the internal limiting membrane on WOCT at the macular, upper, and lower regions. Image analysis software was also used for cell counting.ResultsA strong correlation was seen between human and software counts. Pearson's correlation coefficient (PCC) was performed to compare categorial variables (on macular +0.866; upper cavity +0.713; lower cavity +0.568; total vitreous cavity +0.834; PConclusionsVitreous number of hyperreflective particles (cells) findings on WOCTcorrelated well with human and software cell counts. Vitreous cells findings on WOCT also correlated with IL-6 concentrations on macular.

Abstract Purpose The present study assesses the utility of en-face widefield optical coherence tomography angiography (OCTA) imaging for evaluating the retinal vascular network during the course of treatment in acute retinal necrosis(ARN). Observations OCTA images of two cases of acute retinal necrosis were analyzed. Case 1 was a 15-year-old male with visual crowding in his right eye who had best-corrected visual acuity of 16/20 and intraocular pressure of 25 mmHg in his right eye on initial evaluation. Case 2 was a 57-year-old male with visual crowding in his left eye who had best-corrected visual acuity of 20/20 in his left eye on initial examination and intraocular pressure of 19.3 mmHg. In both patients, dynamic changes could be tracked by en-face ultra-widefield OCTA imaging before and up to 1 year after surgical treatment. The images showed arteriovenous anastomosis and the nonperfused area on the surface of the retina. Conclusions and importance En-face widefield OCTA is useful for monitoring the structure of retinal vessels over time in acute retinal necrosis. Wide-angle OCTA is used to non-invasively examine retinal vascular dynamic changes in ARN. OCTA artifacts due to intraocular inflammation appeared, making interpretation difficult. These will remain as issues in the future. It seems difficult for a while to completely replace FA due to the problem of image clarity.

The aim was to investigate the structural changes of the retina using en face ultra-widefield optical coherence tomography (OCT) images during the treatment of hypotony maculopathy with traumatic cyclodialysis. Case 1 was a 43-year-old male patient with visual crowding in his left eye (metallic wire injury that occurred 3 weeks previously) who was referred to our department. Although best-corrected visual acuity was 20/20 in his left eye on initial evaluation, intraocular pressure was 6 mm Hg. Case 2 was a 20-year-old male patient with visual crowding in his left eye (baseball ball injury that occurred 4 weeks previously) who was referred to our department. Although best-corrected visual acuity was 16/20 in his left eye on initial examination, intraocular pressure was 5 mm Hg. Surgical interventions were performed in both cases. En face ultra-widefield OCT images were able to be used to trace dynamic changes before the intervention and up to 1 year later. The images obtained in these two cases made it possible to confirm the progress from wrinkles on the surface of the retina to normalization of vascular structure and improvement of ellipsoid zone disruption. En face ultra-widefield OCT is useful for monitoring multilayer structures of the retina in hypotony maculopathy cases.

Abstract The purpose of this study was to investigate the occurrence rate and predictors of photodynamic therapy (PDT) induced acute exudative maculopathy (PAEM). This retrospective study included 39 eyes of 39 patients (32 males and 7 females), who were treated with initial PDT. PAEM was defined as an increase in central retinal thickness (CRT) of 15% or more measured by OCT on day 3 after PDT compared with baseline. Sixteen of 39 eyes (41%) were classified in the PAEM+ group. CRT and central choroidal thickness (CCT) were significantly increased at 3 days in the PAEM+ group and significantly decreased at 1 month after PDT in the PAEM- group. In a multiple comparison, neovascular age-related macular degeneration (nAMD) had a significantly higher incidence of PAEM compared to polypoidal choroidal vasculopathy (PCV) and central serous chorioretinopathy (CSC). The incidence of PAEM was lower in PCV and CSC, and higher in nAMD. BCVA at 1 month was significantly worse in the PAEM group, which may be related to visual prognosis after PDT. Since both CRT and CCT decrease at 1 month, the detection of PAEM needs to be assessed a few days after PDT.

The aim of the study was to report a case of traumatic medial longitudinal fasciculus (MLF) syndrome diagnosed with brain magnetic resonance imaging (MRI) after a head injury. A 71-year-old male complained of diplopia after he was bruised the back of his head when he was hit by a bicycle and fell down. He showed failure of adduction in the right eye, and mild nystagmus was found in the left eye when looking to the left. Convergence was intact. A low-intensity area was found at the middle right site in the lower part of the midbrain using thin-section MRI with susceptibility-weighted imaging (SWI), which suggested a hemorrhage. From the present history, characteristic abnormality of eye movement, and MRI imaging, he was diagnosed with traumatic MLF syndrome. His symptom was resolved, and the eye movement was improved in 2 weeks. A hemorrhage that occurs in the brainstem may be a cause of traumatic MLF syndrome which could be detected by thin-slice MRI with SWI.

Abstract Background Diagnostic vitrectomy is an important method for evaluating uveitis, and its diagnostic utility is high regardless of whether the uveitis is infectious or non-infectious. The course of diagnostic vitreous surgery with 27-gauge pars plana vitrectomy and perioperative complications is reported. Methods An observational retrospective study of patients who underwent 27-gauge diagnostic vitrectomy due to atypical intraocular inflammation was conducted. The final diagnosis rate, complications due to surgery, preoperative visual acuity, and postoperative visual acuity (1 month and 6 months after surgery) were examined retrospectively. Results Diagnostic vitreous surgery was performed in 32 patients and 35 eyes (14 males and 18 females, age 14–85 years, median 67 years) during the study period. The average operation time was 52 min for 19 eyes with cataract surgery and 35 min for 16 eyes without cataract surgery. Preoperative log(minimum angle of resolution [MAR]) visual acuity was 0.84 ± 0.87, 1-month postoperative logMAR visual acuity was 0.41 ± 0.55 (p = 0.004, n = 28), and 6-month postoperative average logMAR visual acuity was 0.45 ± 0.73 (p = 0.012, n = 15). The diagnosis was made by diagnostic vitrectomy in 19 cases (54%). Postoperative complications were observed in 2 of 35 postoperative patients (5%); one involved increased intraocular pressure, and the other case involved vitreous hemorrhage of the eye, necessitating reoperation. Conclusion Diagnostic 27-gauge vitrectomy could be effective for evaluating intraocular inflammation.

PurposeTo confirm the utility of ultra-widefield optical coherence tomography (W-OCT) for diagnosing uveitis.MethodWe retrospectively studied patients who had been diagnosed with uveitis and had undergone W-OCT. All patients had visited at Osaka Metropolitan University between January 2019 and January 2022. On W-OCT, vitreous opacity ("W-OCT VO") and the presence of vitreous cells ("W-OCT Cells") were identified by three specialists. We compared findings from ophthalmoscopy ("Ophthalmoscopic findings") and fluorescein angiography ("FAG findings") with those from W-OCT.ResultsThis study investigated 132 eyes from 68 patients (34 males, 34 females; mean age, 53.97±22.71 years). Vitreous cells in posterior uveitis and panuveitis differed significantly between "W-OCT Cells" and "Ophthalmoscopic findings" for all cases (P = 0.00014). Vitreous opacities in posterior uveitis and panuveitis did not differ significantly between "W-OCT VO" and "Ophthalmoscopic findings" (P = 0.144) for all cases. Compared to "Ophthalmoscopic findings", "W-OCT Cells" offered 51.1% sensitivity and 66.7% specificity for all cases (pConclusionW-OCT was shown to offer significantly greater sensitivity than ophthalmoscopy for detecting vitreous cells. The results of this study may add an option for the evaluation of uveitis.

Abstract Purpose Human leukocyte antigen (HLA) and immunity are related. Uveitis is also closely related to immunity. For example, the common presence of human leukocyte antigen (HLA)-DRB1*04 in the immune response is well known. The aim of this study was to investigate the relationship between visual prognosis and various HLA alleles before and after therapy in patients with unclassifiable uveitis, excluding those with Vogt-Koyanagi-Harada (VKH) disease. Methods This retrospective case series included 42 eyes from 22 consecutive patients with unclassifiable uveitis, excluding those with VKH disease. Visual acuity (VA), sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and 6-month visits. Mean values of parameters were compared at each visit. Genotyping was performed by polymerase chain reaction amplification with sequence-specific primers. Results DRB1*04 showed a dominant change. No significant difference was observed in the other alleles. In DRB1*04, The mean differences in initial CCT, 6-month CCT, and 6-month VA showed statistically significant difference was found in best-corrected visual acuity (BCVA) between DRB1*04+ and DRB1*04− at the first visit. BCVA values at baseline and at the final visit were 0.13 ± 0.29 and 0.20 ± 0.36 in the DRB1*04+ and 0.00045 ± 0.20 and − 0.058 ± 0.11 in the DRB1*04− groups(p = 0.00465). Central Choroidal Thickness (CCT) values pretreatment and at the final visit after treatment were (pretreatment:361.00 ± 361.0 μm,after treatment: 286.00 ± 106.53 μm, p = 0.0174) in the DRB1*04+ group, and (pretreatment:281.3 ± 139.68 μm,after treatment:223.85 ± 99.034 μm, p = 0.0426) in the DRB1*04− group, respectively, indicating changes between baseline and the final visit. CCT was significantly greater in the DRB1*04+ group at both the initial visit and at 6 months. Multivariate analysis showed a significant difference between the presence or absence of DRB1*04 and sex. Conclusion HLA-DRB1*04 allele may affect visual prognosis and CCT in unclassifiable uveitis.

Purpose: To report a case of fundus white spots associated with graft-versus-host disease (GVHD) during the remission phase of acute myelogenous leukemia (AML). Observations: A 60-year-old woman was diagnosed with AML 7 months earlier, and after 3 months of chemotherapy, she underwent bone marrow transplantation 2 months earlier and was in remission. When she first came to our department with the chief complaint of persistent bilateral floaters before she developed AML, she had a skin rash caused by GVHD that had been diagnosed 4 days earlier, and the fundi of both eyes showed multiple white spots in the deep retinal layers. One month later, the GVHD skin rash had resolved with topical steroid treatment, and the fundus white spots had mostly disappeared. Fifteen months after the initial visit, the fundus white spots had completely disappeared, with remaining hypofluorescent dots on fundus autofluorescence. Her best-corrected visual acuity was 1.2 in each eye at the first visit and remained at 1.0 in the right eye and 1.2 in the left eye at the final visit 15 months later. Conclusions and importance: Fundus white spots may occur in the early phase of GVHD, causing focal retinal pigment epithelium atrophy after resolution.

Purpose: To report a case of angioid streaks that showed non-exudative choroidal neovascularization (CNV) after the onset of acute retinopathy in pseudoxanthoma elasticum (PXE). Observations: A 64-year-old woman with PXE visited our department for an ophthalmologic evaluation. Her decimal best-corrected visual acuity (BCVA) was 1.5, with angioid streaks (AS) around the optic disc in either eye at the first visit. Seven years later, her left eye's BCVA suddenly decreased by 0.3, and the fundus showed blurring of the Ellipsoid zone and vitreous cells along with the retinal pigment streaks on the nasal fovea. Diagnosed as acute retinopathy in PXE, twenty-two weeks after the start of oral prednisolone, the Ellipsoid zone became clear and the BCVA improved to 1.2, but CNV gradually developed. After intravitreal injection of bevacizumab, the CNV was decreased. Conclusions and importance: CNV on the AS lesion may occur after acute retinopathy in PXE.

Abstract The chronic eye disorder, neovascular age-related macular degeneration (nAMD), is a common cause of permanent vision impairment and blindness among the elderly in developed countries, including Japan. This study aimed to investigate the disease burden of nAMD patients under treatment, using data from the Japan National Health and Wellness surveys 2009–2014. Out of 147,272 respondents, 100 nAMD patients reported currently receiving treatment. Controls without nAMD were selected by 1:4 propensity score matching. Healthcare Resource Utilisation (HRU), Health-Related Quality of Life (HRQoL), and work productivity loss were compared between the groups. Regarding HRU, nAMD patients had significantly increased number of visits to any healthcare provider (HCP) (13.8 vs. 8.2), ophthalmologist (5.6 vs. 0.8), and other HCP (9.5 vs. 7.1) compared to controls after adjusting for confounding factors. Additionally, nAMD patients had reduced HRQoL and work productivity, i.e., reduced physical component summary (PCS) score (46.3 vs. 47.9), increased absenteeism (18.14% vs. 0.24%), presenteeism (23.89% vs. 12.44%), and total work productivity impairment (33.57% vs. 16.24%). The increased number of ophthalmologist visits were associated with decreased PCS score, increased presenteeism and total work productivity impairment. The current study highlighted substantial burden for nAMD patients, requiring further attention for future healthcare planning and treatment development.

Abstract The purpose of this study was to investigate the factors of clinical outcome of selective retina therapy (SRT) for central serous chorioretinopathy (CSC). This retrospective study included 77 eyes of 77 patients, who were treated with SRT for CSC and observed at least 6 months after the treatment. SRT laser (527 nm, 1.7 µs, 100 Hz) was used for treatment. The mean best-corrected visual acuity (logMAR), central macular thickness (CMT) and central choroidal thickness were changed from baseline to at 6-months follow-up with significant difference. The multivariate analyses found that the rate of change (reduction) in CMT was associated with focal leakage type on fluorescein angiography (FA) (p = 0.03, coefficient 15.26, 95% confidence interval 1.72–28.79) and larger baseline CMT (p

Abstract Introduction To evaluate 1-year outcomes of intravitreal aflibercept (IVA) using a treat-and-extend (TAE) regimen for polypoidal choroidal vasculopathy (PCV) and identify the factors for patients whose treatment intervals could be extended. Methods Fifty-one eyes of treatment-naïve PCV patients treated with IVA using a TAE regimen for at least 1 year were examined retrospectively. All patients received at least three IVA injections every 5 weeks, and the intervals were then extended by 2-week adjustments up to 13 weeks. When retinal exudation recurred, the patient was treated with the same regimen, but with a shortened interval of 5 weeks. The main outcome measures were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) as well as the treatment interval at 1 year. Results The mean logarithm of the minimum angle of resolution BCVA improved from 0.24 ± 0.32 at baseline to 0.18 ± 0.31 at 12 months (p = 0.048). The mean CRT decreased from 350.3 ± 147.7 µm at baseline to 215.3 ± 75.0 µm at 4 months (p

Purpose: To report a case with rapid regression of scleral melting associated with tumor necrosis factor-α (TNF-α) in a surgically induced necrotizing scleritis (SINS) patient treated with local steroid therapy. Case Presentation: An 85-year-old male patient presented with conjunctival tumor in his right eye. Complete resection of the tumor lesion and conjunctival re-construction were performed. Local steroid drops were administered until 1 month after surgery, and a good clinical course was achieved. However, after stopping the local steroid, scleral melting to the uvea occurred on the center of the tumor-resected sclera. After diagnosing SINS, we immediately restarted his local steroid. After 2 weeks, there was a complete and rapid regression of the scleral melting. Following this episode, only local steroid therapy was continued for the treatment of SINS, with no recurrence observed after 6 months. Histopathological analysis revealed the infiltration of inflammatory cells during the acute phase, with TNF-α immune reactivity observed in the center of the melting site near the resected conjunctiva. Conclusion: We speculate that the observed changes were associated with the TNF-α that was present during the pathological state of SINS. Local steroid therapy may play a key role in the local immune balance in SINS.

Abstract Background To investigate preoperative clinical factors and visual outcomes of Japanese patients with dysthyroid optic neuropathy (DON) after urgent orbital decompression. Methods This retrospective, observational case series study investigated 44 patients who exhibited several preoperative clinical factors that might be associated with the need for urgent orbital decompression due to DON. Additionally, the visual acuity of DON patients was compared between the patients preoperatively and at 1 and 6 months postoperatively. Results All 44 patients received steroid and with or without radiation therapy, with 27 patients able to avoid undergoing urgent surgery. However, the remaining 17 patients required urgent orbital decompression following a lack of response to the therapy. None of the patients who initially avoided surgery required additional surgery for DON. Factors significantly associated with the need for urgent orbital decompression surgery included: female gender, older age, long disease duration, unilateral significant DON, history of resistance to pulsed steroid therapy, unstable thyroid function, high TRAb (Thyrotrophin receptor antibody)value, poor visual acuity, presence of central diplopia, and presence of corneal problems (P

Individuals with pachydrusen, larger than 125 μm, have a significantly thicker choroid than do those with soft drusen or reticular pseudodrusen. Little is known about cases of abnormal blood flow within pachydrusen. The purpose of this report was to demonstrate a blood flow signal within pachydrusen using optical coherence tomography (OCT) angiography. A 76-year-old Japanese woman presented with innumerable drusen/pachydrusen in both posterior poles. Her visual acuity was good. OCT showed subfoveal pachydrusen in the left eye, but no exudative changes. The subfoveal choroidal thickness was increased to 274 μm in the left eye. OCT angiography revealed a blood flow signal within the pachydrusen. However, fluorescein and indocyanine green angiographies indicated no abnormal hyperfluorescent lesion in the macula of the left eye. During the 13-month follow-up, the blood flow signal in OCT angiography did not change in diameter, and no exudative change was observed. The blood flow signal may have properties of capillary blood vessels derived from the choriocapillaris, rather than angiogenic vessels from choroidal neovascularization or polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization.

Conjunctival squamous cell carcinoma (SCC) is the most common ocular surface neoplasia. The purpose of this retrospective study was to examine the role of regulatory T cell (Treg) activity in tumor immunity and investigate the tumor microenvironment as a new treatment focus in conjunctival SCC. Cancer progression gene array and immunohistochemical analyses of FOXP3 as a Treg marker, CD8 as a tumor-infiltrating lymphocyte marker, and CXCR4 expression on activated Tregs were conducted in a series of 31 conjunctival SCC cases. The objective was to investigate the immunoreactive response in tumor cells and stromal cells in the cancer microenvironment. The stroma ratio in tumor cells was investigated by monitoring α-smooth muscle actine (SMA) expression between carcinoma in situ (Tis) and advanced carcinoma (Tadv) (P

Purpose Diabetic patients often have systemic circulation diseases which may cause serious systemic complications during ophthalmic surgeries with local anesthesia. The purpose of this study is to evaluate the intraoperative alteration of the vital signs in diabetic patients during cataract surgery with local anesthesia. Methods Clinical records of 428 patients who underwent cataract surgeries with local anesthesia were reviewed. The parameters measured were systolic/diastolic blood pressures and pulse rates at pre-operation, 5, 10 and 15 minutes during the surgeries. The factors were compared between non-diabetic patients (n = 325) and diabetic patients (n = 103). Results Diabetic patients had significantly higher fasting blood sugar and preoperative pulse rate. Diabetic patients showed significantly higher systolic blood pressure compared to non-diabetic patients at 5 and 10 minutes from the beginning of surgery (p = 0.0093 and 0.0075, respectively). In the non-diabetic patients, the pulse rate was significantly decreased at 5 minutes from the beginning of surgery (p = 4.74 x 10−8) which was maintained during the surgery, but no change was observed in the pulse rate of the diabetic patients. Conclusions Diabetic patients showed higher systolic blood pressure and pulse rate during cataract surgeries with local anesthesia, which should be monitored carefully by the physicians to avoid possible systemic complications.

The purpose of this study was to compare the safety and efficacy of selective retina therapy (SRT) combined with the intravitreal injection of ranibizumab (IVR) in patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO). This trial was a 12-month single-center, randomized, single-masked prospective study. Eligible patients were randomized (1:1) to IVR and SRT (IVR + SRT group), or IVR and sham SRT (IVR + sham group). After the initial IVR, all participants received ME resolution criteria-driven pro re nata treatment. SRT or sham SRT was always applied one day after IVR. The primary outcome measure of this study was the mean change in central macular thickness (CMT) from baseline, and the secondary outcome measures were the mean change in visual acuity from baseline and the number of IVR treatments at a 52-week follow-up. Thirteen patients were in the IVR + SRT group, and 11 were in the IVR + sham group. Compared to the baseline, mean CMT and BCVA improved significantly after 52 weeks in both groups, with no significant difference between the two groups. The mean number of IVR was 2.85 ± 1.52 in the IVR + SRT group and 4.73 ± 2.33 in the IVR + sham group at the 52-week follow-up, with a significant difference between the two groups (p < 0.05). IVR combined with SRT may significantly decrease the number of IVR treatments while maintaining the visual and anatomical improvement effect of IVR monotherapy.

Abstract Background The common presence of human leukocyte antigen (HLA)-DRB1*04 in Vogt-Koyanagi-Harada (VKH) disease is well known. The aim of this study was to investigate the relationship between visual prognosis and HLA-DRB1*04 alleles during systemic corticosteroid therapy in patients with VKH disease. Methods This retrospective case series included 57 eyes from 29 consecutive patients with treatment-naïve VKH disease who received systemic corticosteroid therapy. Visual acuity, sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and final visits. Mean values of parameters were compared with each visit. Genotyping was performed by polymerase chain reaction amplification with sequence-specific primer. Results Linear regression showed significant differences in logMAR best-corrected visual acuity between the three groups of homozygotes, heterozygotes, and normal subjects at baseline (p

Purpose: To report a case of a patient with subretinal fluid (SRF) associated with choroidal nevus (CN), who was treated with selective retina therapy (SRT) and ultimately achieved resolution of the SRF. Observations: A 41-year-old man with SRF associated with CN in his right eye (RE) underwent ophthalmologic evaluation, including optic coherence tomography, fluorescein angiography (FA) and indocyanine green angiography. The best corrected visual acuity (BCVA) converted to the logarithm of the minimum angle of resolution (logMAR) was 0.00 in the RE. SRT (532 nm, 1.7 μs pulse duration, 30 pulses in 100Hz; Medical Laser Center Lübeck) was performed with the laser spots equally distributed across the FA leakage area. Until 20 months SRT was repeated several times because the SRF decreased every time in response to SRT, but was not completely resolved and sometimes increased with time. After performing 6 times of SRT session, leakage on FA stopped at 21 months follow-up and SRF was resolved at 31 months. At 60 months after the first SRT, there were no signs of malignant transformation, no SRF, and the BCVA in the RE was 0.22. Conclusions and Importance: SRT seems to be a useful treatment and proper clinical studies are necessary to establish the best treatment protocol for SRF associated with CN.

PurposeConjunctival squamous cell carcinoma (SCC) is primarily treated with surgical resection. SCC has various stages, and local recurrence is common. The purpose of this study was to determine molecular localization of epidermal growth factor receptor (EGFR) and the possibility of EGFR as a biomarker for the management of conjunctival SCC.MethodsIn this retrospective study, we performed immunohistochemistry to evaluate EGFR expression and localization in tumor cells, EGFR mutation-specific expression (E746-A750del and L858R), and human papillomavirus expression in a series of 29 conjunctival SCCs.ResultsAll 29 tumors in our cohort were EGFR positive (100%). Twenty-one of 29 tumors (72%) showed focal EGFR staining, and seven (28%) showed diffuse EGFR staining. In addition, we calculated the percentages of the two most important mutations in EGFR (exon 19 746-A750del (8/29, 27.5%), exon 21 (L858R mutant (2/29, 6.8%)) in conjunctival SCCs. We observed that the translocation of EGFR from the membrane into the cytoplasm was related to clinical prognosis, as we detected correlations between EGFR cytoplasmic staining and final orbital exenteration and between decreased EGFR membrane staining and progression-free survival.ConclusionsEGFR is important in the pathology of ocular surface squamous neoplasia including SCC and is a prognostic factor. Increased understanding of EGFR mutations may have important implications for future treatment options.

Purpose: To report a case of polypoidal choroidal vasculopathy associated with optic disc coloboma. Methods: Case report. Results: A 50-year-old woman presented with optic disc coloboma and retinochoroidal coloboma associated with subretinal hemorrhage and serous retinal detachment (SRD) in her left eye. Optical coherence tomography (OCT) confirmed SRD at the macula and showed a sharply elevated retinal epithelial detachment at the choroidal excavation. OCT also revealed choroidal cavitation along the temporal side of the optic coloboma. Fluorescein angiography showed hyperfluorescent dye leakage and indocyanine green angiography revealed polypoidal lesions. We diagnosed polypoidal choroidal vasculopathy (PCV). PCV was located at the end of the choroidal cavitation. Her left eye was treated with an intraocular injection of the anti-vascular endothelial growth factor aflibercept (2 mg). Photodynamic therapy was performed using the standard protocol 1 week after the intravitreal application of aflibercept. One month after the combined treatment, OCT showed completely resolved SRD and her symptoms disappeared. Her best-corrected visual acuity remained stable and no recurrence was found during a 12-month follow-up period. Conclusion: PCV associated with optic disc coloboma has not been previously reported. The morphological abnormality of choroidal cavitation and choroidal excavation connecting with optic disc coloboma may contribute to the development of PCV in this case.

Abstract We conducted a genome-wide association study (GWAS) on the outcome of anti-VEGF treatment for exudative age-related macular degeneration (AMD) in a prospective cohort. Four hundred and sixty-one treatment-naïve AMD patients were recruited at 13 clinical centers and all patients were treated with 3 monthly injections of ranibizumab followed by pro re nata regimen treatment for one year. Genomic DNA was collected from all patients for a 2-stage GWAS on achieving dry macula after the initial treatment, the requirement for an additional treatment, and visual acuity changes during the 12-month observation period. In addition, we evaluated 9 single-nucleotide polymorphisms (SNPs) in 8 previously reported AMD-related genes for their associations with treatment outcome. The discovery stage with 256 patients evaluated 8,480,849 SNPs, but no SNPs showed genome-wide level significance in association with treatment outcomes. Although SNPs with P-values of

Aim: To report a case of choroidal neovascularization secondary to unilateral retinal pigment epithelium dysgenesis (URPED), which was resistant to posterior subtenon injection of triamcinolone acetonide (STTA) and intravitreal bevacizumab injection (IVB). Case Report: An 8-year-old boy was referred to us because of a unilateral unique clinical appearance on funduscopic examination in his left eye (OS). A geometric lesion at the retinal pigment epithelium level of the interpapillomacular area was disclosed OS. The optic nerve was slightly hyperemic OS. Findings from the right fundus examination were normal. Based on these characteristic findings, he was diagnosed as having URPED. Best corrected Landolt ring chart visual acuity (BCVA) was 1.0 in both eyes. Twenty-three months after the first visit, the patient presented with visual disturbance OS. Funduscopic examination showed an expansion of the geometric lesion and the development of a subfoveal choroidal neovascularization (CNV). BCVA was 0.4 OS. Two-time STTA (40 mg/1 ml) was performed at the onset of CNV and 6 months later, and additional IVB (1.25 mg/0.05 ml) was done 10 months later for the treatment of CNV, but the geometric lesion and CNV were resistant to the treatment and continued to expand. Seven years after the first visit, the geometric lesion and the CNV kept expanding steadily. Conclusion: URPED is a rare clinical entity, and the prognosis of this disease is still unclear. The visual prognosis may depend on whether CNV fully develops.

Purpose: To report a case who had recurrence of macular hole retinal detachment (MHRD) after intravitreal ranibizumab injection (IVR) for the treatment of choroidal neovascularization (CNV) that arose from the damaged retinal pigment epithelium of the remaining macular hole (MH) edge, which had been successfully treated by pars plana vitrectomy (PPV) 15 years previously. Case Report: A 67-year-old man with previous PPV for MHRD secondary to high myopia in the right eye had been under observation for 15 years after surgery. The retina had been successfully attached, but the MH remained open. He had CNV which arose from the remaining MH edge. IVR was performed for the treatment of CNV. One month after the injection, CNV was contracted but recurrence of MHRD occurred. PPV with an additional internal limiting membrane peeling, removal of the CNV membrane and 20% SF6 gas tamponade was performed. One year after the last surgery, his right retina was attached and the MH was closed successfully. Conclusion: We propose that patients who undergo IVR should be carefully maintained and followed up for possible complications including the recurrence of MHRD.

Purpose: To report a case of proliferative diabetic retinopathy (PDR) showing transient macular edema (ME) and deteriorated retinal function after intravitreal bevacizumab injection (IVB). Methods and Results: A 53-year-old man received IVB (1.25 mg/0.05 ml) in both eyes for the treatment of PDR. There was no treatment-related complication. However, he complained of photopsia in both eyes 6 h after the injection. Slit-lamp examination revealed mild cellular infiltrations (1+) in the anterior chamber in both eyes. Optical coherence tomography showed ME formation in the left eye. Both full-field and multifocal electroretinography (ERG) revealed the deterioration of all parameters in both eyes compared with pretreatment. The inflammation in the anterior segment and ME disappeared 1 day after the injection. ERG parameters were improved 9 days after the injection, except for the N1 and P1 amplitude of multifocal ERG in the left eye. Conclusion: We propose that patients who undergo IVB should be carefully informed and followed up for possible complications including temporal ME formation and retinal function deterioration.

Purpose: To describe the ophthalmic findings in the fundus of a Japanese infant with Potter sequence having a mutation in the PAX2 gene. Methods: A 1-month-old infant diagnosed with Potter sequence who had bilateral renal hypoplasia and a mutation in the PAX2 gene was subjected to detailed ophthalmic examination. Results: Funduscopy revealed a megalopapilla with marked excavation in the right eye. The left optic disc showed a similar abnormality, but to a lesser extent. B-mode ultrasonography and magnetic resonance imaging detected giant cystic lesions occupying the optic nerve head in both eyes. According to these results, we diagnosed this patient as having papillorenal syndrome (PRS) associated with a PAX2 mutation. Conclusions: This report shows ophthalmic findings in the youngest patient with PRS and PAX2-associated Potter sequence. Optic disc anomalies may be involved in some infants with Potter sequence. We anticipate an increase in opportunities for ophthalmic examinations in infants with diseases such as Potter sequence with previously high mortality rates.

Purpose: Idiopathic macular holes (MHs) may occur bilaterally, and the spontaneous closure of MHs was documented previously. The median interval between the onset of MHs in each eye was reported to be 17.5 months. Method: We report a case of bilateral MHs which occurred and resolved spontaneously over a very short interval. Results: A 48-year-old woman with no history of ocular disease complained of a central scotoma and metamorphopsia in the left eye. Stage 1A MH was diagnosed in the left eye on the initial visit, which resolved spontaneously with vitreofoveal separation after 1 month. After an additional month, she complained of a similar visual disturbance in the right eye. Stage 1B MH was found in the right eye, which showed spontaneous closure after 1 month in the same manner as the left eye. Conclusion: We present a unique case of bilateral MHs which occurred and resolved spontaneously within a very short time period. Careful observation of the non-involved eye is needed to address the risk of early onset bilateral MHs.

To compare the association of elastin (ELN) gene variants between two different angiographic phenotypes of polypoidal choroidal vasculopathy (PCV).We included 411 treatment-naïve PCV patients and 350 controls in the present study. PCV was classified into two phenotypes (152 Type 1 and 259 Type 2) according to the presence or absence of feeding vessels found in indocyanine-green angiography. Single nucleotide polymorphisms (SNPs) in the ELN region including rs868005, rs884843, rs2301995, rs13239907 and rs2856728 were genotyped using TaqMan Genotyping Assays.In the allelic association analyses, rs868005 showed the strongest association with Type 2 PCV (allelic odds ratio 1.56; p = 7.4x10(-6)), while no SNP was significantly associated with Type 1 PCV. Genotype association analyses revealed the significant association of rs868005 with Type 2 PCV in log additive model and predominant model (odds ratio 1.75; p = 1.5x10(-6) and odds ratio 1.60; p = 0.0044, respectively), but not with Type 1 PCV. These findings were further corroborated by another control group in the literature.There may be significantly different associations in genetic variants of elastin between two angiographic phenotypes of PCV.

Purpose. To evaluate the early response to intravitreal ranibizumab (IVR) in two different phenotypes of age-related macular degenerations (AMD): typical neovascular AMD (tAMD) and polypoidal choroidal vasculopathy (PCV). Methods. Sixty eyes from 60 patients (tAMD 28, PCV 32 eyes) were recruited. Three consecutive IVR treatments (0.5 mg) were performed every month. Change in the best-corrected visual acuity (BCVA) and central retinal thickness (CRT) was then compared between the tAMD and PCV groups. Results. The mean BCVA logMAR was significantly improved at month 1 and month 3 after the initial IVR in the tAMD group, but there was no change in the PCV group. Both phenotypes showed significant improvements in the CRT during the 3 months after the initial IVR. There were no significant differences in the improvements of the CRT in the tAMD versus the PCV group. In the stepwise analysis, a worse pretreatment BCVA and tAMD lesions were significantly beneficial for a greater improvement of BCVA at 3 months after the initial IVR. Conclusions. The phenotype of tAMD showed a significantly better early response to IVR than PCV in terms of BCVA improvement.

BACKGROUND: Genetic variants in the complement component 3 gene (C3) have been shown to be associated with age-related macular degeneration (AMD) in Caucasian populations of European descent. In particular, a nonsynonymous coding variant, rs2230199 (R102G), is presumed to be the most likely causal variant in the C3 locus based on strong statistical evidence for disease association and mechanistic functional evidence. However, the risk allele is absent or rare (

Purpose. Choroidal neovascularization (CNV) is often associated with age-related macular degeneration (AMD) and pathological myopia (PM). Bisphosphonates, the drug of choice to treat osteoporosis, have been recently reported to have anti-angiogenic effects. The purpose of this study is to investigate the therapeutic effects of oral bisphosphonates for CNV in humans. Methods. Thirty-six consecutive cases with CNV due to AMD or PM who declined anti-VEGF therapy were recruited. The patients were prescribed 5 mg of oral alendronates daily for 6 months. The best-corrected visual-acuity (BCVA), the lesion size in fundus photographs and fluorescein angiography, foveal thickness and total macular volume in optical coherence tomography were compared between pre- and post-treatment. Results. The mean BCVA of the patients was significantly improved after a months with the treatment in the AMD group. In the PM group, the mean BCVA was maintained up to 6 months with the treatment. The mean lesion size was significantly decreased by 3 months in both groups. The averages of foveal thickness and total macular volume were significantly reduced after 1 month of treatment in the AMD group.Conclusions. Oral bisphosphonate should be further investigated as a possible therapeutic and preventive drug for CNV due to AMD and PM.