Period prevalence of uveitis in human T-lymphotropic virus 1 carriers versus noncarriers in a highly endemic area: The Nagasaki Islands Study.

The magnitude of the effect of human T-lymphotropic virus 1 (HTLV-1) infection on uveitis remains unclear. We conducted a cross-sectional study in a highly endemic area of HTLV-1 in Japan. The study included 4265 residents (men, 39.2%), mostly middle-aged and older individuals with a mean age of 69.9 years, who participated in our surveys between April 2016 and September 2022. We identified HTLV-1 carriers by screening using chemiluminescent enzyme immunoassays and confirmatory tests, and the proportion of carriers was 16.1%. Participants with uveitis were determined from the medical records of all hospitals and clinics where certified ophthalmologists practiced. We conducted logistic regression analyses in an age- and sex-adjusted model to compute the odds ratio (OR) and 95% confidence interval (CI) of uveitis according to HTLV-1 infection status. Thirty-two (0.8%) participants had uveitis. For HTLV-1 carriers, the age- and sex-adjusted OR (95% CI) of uveitis was 3.27 (1.57-6.72) compared with noncarriers. In conclusion, HTLV-1 infection was associated with a higher risk of uveitis among mostly middle-aged and older Japanese residents in a highly endemic HTLV-1 area. Our findings suggest that physicians who treat HTLV-1 carriers should assess ocular symptoms, and those who diagnose patients with uveitis should consider HTLV-1 infection.

Both hemoglobin and hemin cause damage to retinal pigment epithelium through the iron ion accumulation.

Subretinal hemorrhages result in poor vision and visual field defects. During hemorrhage, several potentially toxic substances are released from iron-based hemoglobin and hemin, inducing cellular damage, the detailed mechanisms of which remain unknown. We examined the effects of excess intracellular iron on retinal pigment epithelial (RPE) cells. A Fe2+ probe, SiRhoNox-1 was used to investigate Fe2+ accumulation after treatment with hemoglobin or hemin in the human RPE cell line ARPE-19. We also evaluated the production of reactive oxygen species (ROS) and lipid peroxidation. Furthermore, the protective effect of-an iron chelator, 2,2'-bipyridyl (BP), and ferrostatin-1 (Fer-1) on the cell damage, was evaluated. Fe2+ accumulation increased in the hemoglobin- or hemin-treated groups, as well as intracellular ROS production and lipid peroxidation. In contrast, BP treatment suppressed RPE cell death, ROS production, and lipid peroxidation. Pretreatment with Fer-1 ameliorated cell death in a concentration-dependent manner and suppressed ROS production and lipid peroxidation. Taken together, these findings indicate that hemoglobin and hemin, as well as subretinal hemorrhage, may induce RPE cell damage and visual dysfunction via intracellular iron accumulation.

Factors Associated with Success of Switching to Faricimab for Neovascular Age-Related Macular Degeneration Refractory to Intravitreal Aflibercept.

We investigated the factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The primary endpoint was a more than two-week extension of the treatment interval after 6 months. In addition, factors related to the success or failure of extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes from 43 patients. Extended dosing intervals of >2 weeks were identified in 14 eyes (32.6%). A short dosing interval before switching, absence of polypoidal lesions, and thin central choroidal thickness before switching were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend existing dosing intervals.

Microsporidial keratoconjunctivitis - first outbreak in Japan.

BACKGROUND: Most cases of microsporidial keratoconjunctivitis are found in the Southern hemisphere. Our purpose was to investigate the first outbreak of microsporidial keratoconjunctivitis in Japan among healthy, immunocompetent soccer players from the same team during a 1-month period. CASE PRESENTATION: This study is an observational case series. The medical records were analyzed for five cases with microsporidial keratoconjunctivitis who presented within September 2022. All five cases were males between 28 and 36 years old. These previously healthy individuals belonged to the same football team. Their eyes were considered susceptible to contaminated water or dirt from the turf at game and practice sites. All cases involved unilateral conjunctivitis, with scattered round white lesions that showed positive fluorescein staining in the corneal epithelium. All cases experienced diminution of vision in the affected eye. In three cases, direct smears showed spores of approximately 2-3 µm in diameter. Polymerase chain reaction (PCR) analysis of corneal scrapes revealed partial amplification of microsporidial 18 S ribosomal RNA gene in four cases. Sequences of PCR products from all four cases showed 100% identity with strains of Vittaforma corneae previously reported from an outbreak in Singapore. All cases were treated with topical therapy, including voriconazole, fluorometholone, and levofloxacin. Four eyes underwent corneal scraping. After treatment, all eyes healed without residual opacities. CONCLUSIONS: Only a few sporadic case reports of this disease have previously been reported in Japan. We detected V. corneae in our case series, representing what appears to be the first outbreak of microsporidial keratoconjunctivitis in Japan. Exposure to contaminated water or soil, in addition to inadequate sanitary facilities, represents a potential source of infection. Further investigations to clarify the characteristics of microsporidia seem warranted.

Paracentral acute middle maculopathy in systemic sclerosis and subsequent branch retinal artery occlusion.

Purpose: We report a case of systemic sclerosis-associated paracentral acute middle maculopathy (PAMM) in a young woman who subsequently developed branch retinal artery occlusion. Observations: A 22-year-old woman presented with a paracentral scotoma. Optical coherence tomography (OCT) revealed bilateral paracentral acute middle maculopathy. Upon systemic examination, she was diagnosed with systemic sclerosis (SSc). She subsequently developed branch retinal artery occlusion despite vasodilator medications. After the prescription of aspirin, she did not experience a new event for one year. Conclusion and importance: This case illustrates that SSc may affect the retinal vascular system and vision and cause PAMM. The optimal prophylaxis for patients with recurrent retinal events should be investigated in future studies.

Whole Corneal Descemetocele.

Background and Objectives: To report a case of microbial keratitis complicated by severe corneal melting and whole corneal descemetocele. Methods: A 72-year-old male farmer presented with a right corneal ulcer involving nearly the entire cornea, which was almost completely melted down with the remaining Descemet's membrane (DM). The pupil area was filled with melted necrotic material, with the intraocular lens partially protruding from the pupil and indenting the DM. Corneal optical coherence tomography (OCT) examination revealed a corneal thickness of 37 µm that was attached to its back surface, with the iris and a part of the intraocular lens (IOL) protruding through the pupil. The patient was hospitalized and treated with local and systemic antibiotics until control of the inflammation was achieved. Corneoscleral transplantation plus excision/transplantation of the corneal limbus were performed, and the entire corneal limbus was lamellarly incised. After completely suturing all around the transplanted corneoscleral graft, the anterior chamber was formed. Postoperative treatment included local antibiotics, anti-inflammatory drugs, and cycloplegic drops. Results: There was no recurrence of infection, and the corneal epithelium gradually regenerated and covered the whole graft. Visual acuity was light perception at 6 months after the surgery. The patient was satisfied that the globe was preserved and did not wish to undergo any further treatment. Conclusions: Corneoscleral transplantation is preferred for the treatment of large-sized descemetoceles with active microbial keratitis and extensive infiltrates, especially in cases where the whole cornea has transformed into a large cyst.

Comparison of rabbit corneal changes during different preservation techniques using optisol-GS and airlift.

A previous study suggested that the airlift condition is superior to the Optisol-GS condition for preserving the limbal tissue of the human cornea. The purpose of this research is to investigate a new preservation device that preserves the cornea while separating epithelial and endothelial areas. The differences after preserving the corneal epithelium under different conditions were compared. A total of 24 corneas of New Zealand rabbits were divided into four groups in which the corneal epithelia were submersed in Optisol-GS or under airlift conditions for 1 and 2 weeks at 4 [Formula: see text]C. Transparency, optical coherence tomography (OCT), hematoxylin and eosin (H &E) staining, and epithelial migration tests were used to assess corneal status. The epithelial migration examination showed significantly greater migration ability after the airlift condition. Corneas in the 1-week Optisol-GS group were the most transparent, followed by the 1-week airlift group. OCT showed a progressive increase in corneal thickness to the end of the study. H &E staining showed that the epithelial cells retained intact cellular structure and morphology of the cells for both 1-week-preserved groups. However, there was disruption of the corneal epithelial cell structure for both 2-week-preserved groups. Corneal epithelium preserved under the hypothermic airlift condition was comparable to that under the Optisol-GS condition.

INVESTIGATION OF INCIDENCE AND CAUSES OF ACUTE VISION LOSS DURING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION DURING A FOUR-YEAR FOLLOW-UP.

PURPOSE: To investigate the incidence, risk factors, and outcomes of patients with age-related macular degeneration who experienced acute vision loss despite periodic injections of anti-vascular endothelial growth factor treatment for 4 years. METHODS: This retrospective cohort study included patients who were diagnosed with treatment-naive neovascular age-related macular degeneration and completed a 4-year follow-up. The incidence and risk factors for the occurrence of three or more lines of visual loss at every checkup were investigated. RESULTS: The analysis included 76 eyes of 76 patients. Acute vision loss occurred in 30 eyes (39.5%) over 4 years. Lower baseline best-corrected visual acuity and disrupted ellipsoid zone were independent predictors of vision loss occurrence. Although the causes and timing of visual acuity loss varied, retinal pigment epithelium tears were observed only in the first year. Most patients (86.7%) who experienced vision loss recovered their vision to pre-loss levels at least once; however, the final best-corrected visual acuity was worse than that in the group that did not experience acute vision loss. CONCLUSION: Approximately half of the patients with age-related macular degeneration experienced acute vision loss during a 4-year follow-up, despite continuous anti-vascular endothelial growth factor treatment. Most patients recovered from vision losses temporarily; however, they experienced worse visual outcomes subsequently.

Geometric Morphometrics Can Predict Postoperative Visual Acuity Changes in Patients With Epiretinal Membrane: A Retrospective Study.

Purpose: To investigate the efficacy of the geometric morphometrics method for the evaluation of retinal deformation in patients with epiretinal membrane (ERM) and determine whether the degree of deformation can serve as a predictive factor for postoperative visual outcome. Methods: We retrospectively evaluated data from 29 eyes of 29 patients with primary ERM. Preoperative optical coherence tomography images were compared with images of their normal fellow eyes using the geometric morphometrics thin-plate spline technique. Conventional parameters such as retinal layer thickness and previously reported indices were also measured. The correlation between the preoperative parameters and visual acuity was evaluated. Statistical comparisons were performed using a paired t-test, and associations between the optical coherence tomography image parameters and visual acuity were determined using Spearman's rank correlation coefficient. Results: Bending energy, which was calculated using geometric morphometrics, was significantly associated with visual acuity as well as conventional optical coherence tomography parameters and previously reported indices. Multiple regression analysis showed that bending energy was an independent predictive factor for postoperative visual acuity changes. Conclusions: The geometric morphometrics method is an effective approach for evaluating the severity of ERM and predicting the efficacy of surgery. Translational Relevance: Geometric morphometrics can effectively evaluate retinal deformation in eyes with epiretinal membrane.

Optic disc hemorrhage in a young female following mRNA coronavirus disease 2019 vaccination: a case report.

BACKGROUND: Since the development of the coronavirus disease 2019 vaccine, there have been many reports of its adverse effects. While respiratory symptoms are common, many other symptoms in various organs have been reported. Herein, we report a case of optic disc and retinal hemorrhage that developed immediately after coronavirus disease 2019 vaccination. CASE PRESENTATION: A healthy 18-year-old Japanese female noticed floater in the left eye 1 day after the second vaccination for coronavirus disease 2019 (Pfizer Inc.). Her visual acuity was 20/20 in the left eye, and Goldmann visual field test showed a relative scotoma around blind spot and in the temporal lower quadrant. It was considered due to subretinal hemorrhage and optic disc swelling. Fundus examination revealed retinal and optic disc hemorrhage. Pupillary reflex was intact and central critical flicker was not impaired, indicating that optic nerve was not involved. There was no sign of inflammation, vascular abnormality, nor history of an intense Valsalva maneuver. The hemorrhage resolved spontaneously within 5 months. CONCLUSION: This case expands the clinical presentation of coronavirus disease 2019 vaccination-associated ocular adverse events, and it should be kept in mind when patients with similar symptoms visit clinics. The case report will help clinicians avoid unnecessary and invasive examinations and treatment.

Recurrence of neovascular age-related macular degeneration after cessation of treat and extend regimen.

The appropriate timing of treatment cessation after treat and extend (TAE) regimen for age-related macular degeneration has not been established. This study aimed to investigate the incidence and risk factors of recurrence after cessation of the TAE regimen. We included patients who received and discontinued the TAE regimen, after extension of the treatment interval to ≥ 12 weeks. Forty-nine patients were included in the study. The estimated recurrence rates were 33% at 1 year and 48% at 2 years after treatment cessation, respectively. Good visual acuity at cessation and a large number of injections in the 6 months before cessation were significant risk factors. Higher chances of recurrence were associated with < 0.1 logarithm of the minimum angle of resolution (logMAR) at cessation (P < 0.002). Meanwhile, five patients with visual acuity ≥ 1.0 logMAR at cessation did not show recurrence. Among the 25 recurrences, two lines of vision loss were noted in only two cases after resumed treatment. This study confirmed the importance of the number of injections in reducing recurrence and the association between visual acuity and recurrence. Recurrence is generally well-controlled with resumed treatment.

Toxicity of Amphotericin B in Rabbit Corneal Epithelial Cells Stored in Optisol™-GS: Corneal Epithelial Cell Morphology and Migration.

PURPOSE: To evaluate the toxicity of Amphotericin B (AmB) in Optisol™-GS Corneal Storage Media (Bausch & Lomb) on corneal epithelial cell (CEC) morphology and migration ability. METHODS: Sclerocorneal strips were removed from male Japanese white rabbits, and then stored at 4 °C in Optisol™-GS containing 0 µg/ml of AmB (control group) and 2.5, 5, 25, and 50 µg/ml of AmB (AmB groups; four eyes per group). After 7 days of storage, CEC morphology was evaluated by hematoxylin-eosin staining, immunohistochemical staining (ZO-1), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Moreover, to evaluate CEC migration ability, three corneal blocks (6-8 × 3 mm each) from one preserved cornea were cultured for 24 h, and the area of CEC migration (2 mm at the central region) onto the stromal surface was then measured. RESULTS: At 5, 25, and 50 µg/ml of AmB, deformation and vacuolation of CECs were observed in all preserved corneas. ZO-1 expression was significantly reduced in corneas preserved at AmB concentrations of 25 and 50 µg/ml. TUNEL Labeling Index was significantly increased at AmB concentrations of ≥5 µg/ml. CEC migration was inhibited in a dose-dependent manner at AmB concentrations of 25 and 50 µg/ml compared to the control group. CONCLUSIONS: The addition of AmB to Optisol™-GS can be toxic to CECs and inhibit their migration at a concentration of ≥5 µg/ml. AmB at a concentration of 2.5 µg/ml can be considered safe for the preservation of donor corneal tissue used in corneal epithelial transplantation surgery.

Effectiveness of a photoscreener in identifying undiagnosed unilateral amblyopia at vision screening of 3-year-old children in Japan.

PURPOSE: In Japan a basic preparatory ophthalmic examination is routinely performed for 3-year-old children. This study aimed to determine the value of incorporating a photoscreener into the examination and evaluate parents' satisfaction with the photoscreener examination. STUDY DESIGN: Prospective study. METHODS: Children aged 42-47 months in Nagasaki City, Japan, underwent a visual acuity test by a parent at home and by automated vision screening using a photoscreener at their local municipal health center between October 2018 and March 2019. Subjects were children referred to Nagasaki University Hospital for examination after failing either test. Children previously diagnosed with strabismus and/or amblyopia were excluded. A questionnaire survey evaluated the level of satisfaction with the photoscreener-based screening by parents who attended these examinations at the local municipal health center. RESULTS: Of children who completed the two tests, 52 (failed visual acuity test, 3; failed photoscreener examination, 49) were referred for examination. Of the 49 photoscreener failures, 12 were diagnosed with amblyopia: unilateral amblyopia with anisometropic hyperopia in 10 (83.3%), and bilateral amblyopia with astigmatism and hyperopia in 2 (16.7%). The photoscreener detected all 12 cases of amblyopia, whereas the home-based visual acuity test detected only two cases. More than 80% of 1035 parents were satisfied with the photoscreener examination. CONCLUSION: Unilateral amblyopia with anisometropic hyperopia was easily overlooked with the home-based test but was detectable by photoscreener examination. The photoscreener proved to be an effective screening tool for amblyopia in children and was considered a satisfactory examination by a high proportion of parents.

Clinical practice guidelines for pseudoxanthoma elasticum (2017): Clinical Practice Guidelines for Pseudoxanthoma Elasticum Drafting Committee

Pseudoxanthoma elasticum (PXE) is a progressive hereditary disease that affects tissues such as the skin, retina, blood vessels, and gastrointestinal tracts. Therefore, comprehensive medical care across clinical departments specialized in specific organs is needed to provide the best clinical practices to PXE patients. The Japanese version of clinical guidelines developed by the Japanese Dermatological Association was published in 2017, and aimed to promote equal accessibility of PXE-related medical care. Here, the English version of Japanese guideline is reported, and is intended to be worldwide reference for medical care of PXE.

Effect of inverted internal limiting membrane flap technique on small-medium size macular holes.

Inverted internal limiting membrane (ILM) flap technique was developed to achieve macular hole (MH) closure in large MH and refractory cases. In this study, we evaluate the effect of the technique for small-medium size MH. We recruited patients who underwent vitrectomy for small-medium size (< 400 µm) MH with either inverted ILM flap technique (flap group) or with conventional ILM peeling (peeling group). Using propensity score, 21 eyes of 21 patients in the peeling group were matched against 21 eyes of 21 patients in the flap group. We compared MH closure rate, postoperative visual acuity, and recovery of the external limiting membrane (ELM) and ellipsoid zone (EZ). The MH closure rate was not different between the two groups (flap vs peeling: 90% vs 100%, P = 0.49). Whereas there was no significant difference in visual acuity improvement between the two groups, the flap group showed more disruption of the ELM 3 months after surgery and of the EZ at 3 and 6 months after surgery (P = 0.02, P = 0.03, and P = 0.04, respectively). The result suggested that inverted ILM flap technique does not have additional benefits for small-medium size MHs and may delay recovery of retinal integrity.

Conjunctival Sac Microbiome in Infectious Conjunctivitis.

Acute bacterial conjunctival infections are common, and this study identified the conjunctival bacterial community in infectious conjunctivitis cases seen at the outpatient clinic of Khanh Hoa General Hospital in Nha Trang, Vietnam from October 2016 through December 2017. Conjunctival swabs were collected and tested using conventional culture, PCR, and 16S ribosomal RNA sequencing. The study included 47 randomly selected patients. More than 98% of all DNA reads represented five bacterial phyla. Three of these phyla constituted 92% of all sequences (Firmicutes (35%), Actinobacteria (31%), and Proteobacteria (26%)). At the genus level, there were 12 common genera that constituted about 61% of all sequence reads. Seven of those genera were common (Streptococcus (10%), Cutibacterium (10%), Staphylococcus (7%), Nocardioides (7%), Corynebacterium 1 (5%), Anoxybacillus (5%), and Acinetobacter (5%)), which encompassed 49% of all reads. As for diversity analysis, there was no difference on PERMANOVA analysis (unweighted UniFrac) for sex (p = 0.087), chemosis (p = 0.064), and unclassified eyedrops (p = 0.431). There was a significant difference in cases with bilateral conjunctivitis (p = 0.017) and for using antibiotics (p = 0.020). Of the predominant phyla, Firmicutes had the highest abundance in bacterial conjunctivitis in this study. Pseudomonas as a resident commensal microbiota may have an important role in the prevention of infection.

Retinal Vascular Resistance Significantly Correlates With Visual Acuity After 1 Year of Anti-VEGF Therapy in Central Retinal Vein Occlusion.

Purpose: To investigate whether the resistivity of all retinal vessels, termed total capillary resistance (TCR), after anti-vascular endothelial growth factor (VEGF) treatment was correlated with the outcomes of patients with macular edema secondary to central retinal vein occlusion (CRVO). Methods: In total, 67 patients with nonischemic CRVO were enrolled in this retrospective observational case series. In each patient, we examined visual acuity; central retinal thickness (CRT); mean blur rate (MBR), which represents retinal blood flow velocity; and TCR. MBR and TCR were measured by laser speckle flowgraphy. Results: During the 1-year follow-up period, nine of 67 eyes (13.4%) converted to the ischemic type (converted group), whereas 58 eyes (86.6%) remained unchanged (nonischemic group). Mean CRT significantly decreased in all groups; however, the mean visual acuity significantly improved only in the nonischemic group. Mean MBR significantly increased in the nonischemic group but remained unchanged in the converted group. Mean TCR was significantly reduced in the nonischemic group but remained unchanged in the converted group. Multiple linear regression analysis revealed that MBR and TCR were the independent factors with the strongest and second strongest correlations with visual acuity after treatment, respectively. Conclusions: These findings suggest that measurements of the independent factors MBR and TCR are useful for evaluating anti-VEGF treatments in patients with CRVO. Translational Relevance: Development of clinically relevant technologies.