Lower Eyelid Merkel Cell Carcinoma in a Non-Immunocompromised Young Female: A Case Report.

Introduction: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin tumor associated with Merkel cell polyomavirus and ultraviolet light exposure. MCC typically affects older individuals, and it also influences young patients with immunosuppressive conditions. We report a case of lower eyelid MCC in a non-immunocompromised 37-year-old woman. Case Presentation: A 37-year-old woman presenting with suspected MCC on her right lower eyelid was referred to our hospital for further resection. The patient underwent wide excision with clear margins followed by reconstruction and radiation therapy. The patient has shown no signs of recurrence after 5 months of follow-up. Conclusion: MCC needs to be considered as a possible diagnosis when examining an eyelid tumor in a young patient.

Intraoperative challenges and management of fibrovascular membrane with tractional retinoschisis in proliferative diabetic retinopathy.

BACKGROUND: In severe Proliferative Diabetic Retinopathy (PDR), fibrovascular membrane (FVM) causes macular tractional retinal detachment (MTRD) which threatens vision and eventually leads to blindness. Here we present a case of separation between the inner and outer retina in tractional retinoschisis, induced during intraoperative FVM delamination. CASE PRESENTATION: A 68-year-old woman presented with PDR in the right eye, characterized by a combined FVM and retinal detachment, for which a vitrectomy was performed. Multiple holes, large retinal detachment extending to all quadrants, and white-lined blood vessels with FVM were found during the procedure. When membrane delamination was performed, it strayed into the space between the inner and outer retinal layers without being noticed due to retinoschisis and multiple retinal holes. After removing the FVM and detaching the separated inner retina, fluid-gas and photocoagulation were performed. Retinal reattachment was successfully achieved after surgery, and the postoperative visual acuity was improved and maintained for 26 months postoperatively. CONCLUSIONS: When tractional retinoschisis due to FVM is combined with retinal holes in tractional retinal detachment (TRD), care must be taken to prevent delamination from straying into retinoschisis during separation.

What Happens 20 to 30 years After Radial Keratotomy? Case Series.

ABSTRACT: Radial keratotomy (RK) was commonly performed in the 1980s and 1990s. We aimed to clarify the current status of post-RK refractive correction and treatment. We retrospectively reviewed the charts of 70 patients with a history of RK. Of the 70 patients, 44 were identified for clinical outcomes. Refractive or therapeutic intervention (rigid gas-permeable contact lens fit, spectacle prescription, corneal surgery, and use of pilocarpine hydrochloride for photophobia) was possible in 59% of patients with postoperative visual deterioration after RK; in the remaining 41%, therapeutic intervention was not possible. Rigid gas-permeable contact lens fit for corneal irregular astigmatism was the most common refractive intervention and was effective in 36% of cases in the university hospital.

Continuous Corneal Endothelial Damage by Chlorhexidine Alcohol Used for Disinfection in Nonophthalmic Surgery.

PURPOSE: To report a case of corneal endothelial damage caused by alcohol-containing chlorhexidine gluconate (CG-A) and its progression over time. METHODS: This was a case report. RESULTS: A 22-year-old man underwent neurosurgery under general anesthesia. CG-A (1%) was used for disinfection after the application of corneal protection tape. Postoperatively, the patient presented with hyperemia and swelling of the left conjunctiva and was referred to our department. Initial examination revealed left corneal epithelial erosion and corneal edema, which improved on postoperative day 14. The corneal endothelial cell density (ECD) was 3,345 cells/mm 2 on day 14, decreased rapidly to 2,090 cells/mm 2 on day 42, and slowly reduced to 1,122 cells/mm 2 on day 168. Thereafter, no decrease in ECD was observed. CONCLUSIONS: CG formulations can lead to a persistent decrease in ECD over several months, even after improvement of acute corneal edema.

Spontaneous separation of secondary epiretinal membrane after vitrectomy for retinal detachment.

Purpose: While secondary epiretinal membranes (ERMs) are well-documented postoperative complications following rhegmatogenous retinal detachment (RRD) surgery, literature addressing the mechanisms of spontaneous resolution, particularly in cases involving vitrectomy, remain limited. In this case report, we describe the spontaneous resolution of secondary ERM in an amateur boxer following traumatic RRD surgery. Observations: Pars plana vitrectomy was performed for traumatic RRD in a 20-year-old man. Secondary ERM formation was observed one month after RRD surgery, resulting in retinal distortion. The ERM began to peel spontaneously and disappeared one year after surgery. His visual function did not deteriorate in the meantime. Conclusions and Importance: Spontaneous ERM separation is possible even after vitrectomy. This is the first published observation of the formation and spontaneous disappearance of secondary ERM after vitrectomy without intervention.

A Case of Closure of Recurrent Full-Thickness Macular Hole by Spontaneous Retinal Detachment around the Macular Hole and Gas Tamponade.

Introduction: Here, we present a case of full-thickness macular hole (FTMH) recurrence following two vitrectomies, accompanied by additional internal limiting membrane (ILM) peeling and gas tamponade. Ultimately, FTMH closure was accomplished by spontaneous retinal detachment around the macular hole and gas tamponade alone. Case Presentation: The patient, a 54-year-old woman with a lamellar macular hole, had a visual acuity of 20/100 in her left eye. The treatment regimen included cataract surgery, a 25-gauge pars plana vitrectomy involving ILM peeling, application of the lamellar hole epiretinal proliferation embedding technique, and subsequent gas tamponade. Closure of the lamellar macular hole was observed a month post-surgery, improving visual acuity to 20/40. However, FTMH developed 3 months after the initial surgery, resulting in visual acuity decline to 20/100. A 25-gauge pars plana vitrectomy was performed with extensive ILM peeling and 20% sulfur hexafluoride gas tamponade. FTMH closure was noted within 19 days after reoperation, enhancing visual acuity to 20/66. Approximately 1.5 months after reoperation, a pinhole-shaped macular hole was identified, and the patient opted for follow-up observation due to her refusal to undergo additional surgery. As the macular hole gradually enlarged resembling retinal detachment, outpatient fluid-gas exchange with 14% perfluoropropane was performed 3.5 months after reoperation. The FTMH closed within a week post-gas injection and remained closed for more than 1 year. Consequently, visual acuity in the left eye was sustained at 20/50. Conclusion: We encountered a case that might highlight the significance of releasing subretinal adhesions surrounding a FTMH for successful closure.

Effect of polyp regression and reduction on treatment efficacy in polypoidal choroidal vasculopathy treated with aflibercept.

Intravitreal injection of aflibercept (IVA) has successfully treated polypoidal choroidal vasculopathy (PCV), and polyp morphology is an important indicator of treatment efficacy. However, many studies have not reported the presence or absence of polyp regression and treatment outcomes, and few studies have reported polyp reduction and treatment outcomes in cases with residual polyps. We retrospectively measured the polyp area on indocyanine green angiography images before and after the IVA loading phase and investigated the regression and reduction of polyps and treatment outcomes of 81 eyes with PCV treated with IVA. We investigated the relationship between the presence or absence of complete regression of polyps and the percentage change in the polyp area and treatment outcomes. Eyes with complete polyp regression had significantly better visual acuity improvements compared with baseline at 12 months (P = 0.0108), fewer treatments (P = 0.0024), fewer recurrences during 12-months follow-up (P = 0.0010), and more "dry maculas" at 3 months (P = 0.0048) than eyes in which polyp regression did not occur. A significant correlation was seen only between the percentage of polyp regression and visual acuity at 3 months (P = 0.0395). Regarding IVA therapy for PCV, the presence or absence of complete polyp regression at the end of the loading phase affected the treatment outcome, whereas the degree of polyp reduction in cases of residual polyps had no effect.

Label-free enrichment of human pluripotent stem cell-derived early retinal progenitor cells for cell-based regenerative therapies.

Pluripotent stem cell-based therapy for retinal degenerative diseases is a promising approach to restoring visual function. A clinical study using retinal organoid (RO) sheets was recently conducted in patients with retinitis pigmentosa. However, the graft preparation currently requires advanced skills to identify and excise suitable segments from the transplantable area of the limited number of suitable ROs. This remains a challenge for consistent clinical implementations. Herein, we enabled the enrichment of wild-type (non-reporter) retinal progenitor cells (RPCs) from dissociated ROs using a label-free ghost cytometry (LF-GC)-based sorting system, where a machine-based classifier was trained in advance with another RPC reporter line. The sorted cells reproducibly formed retinal spheroids large enough for transplantation and developed mature photoreceptors in the retinal degeneration rats. This method of enriching early RPCs with no specific surface antigens and without any reporters or chemical labeling is promising for robust preparation of graft tissues during cell-based therapy.

Comparison of the 1-year surgical outcomes of ab interno trabeculotomy using three types of microhooks.

PURPOSE: We compared the 1-year surgical outcomes of microhook ab interno trabeculotomy (µLOT) using three types of microhooks. METHODS: We retrospectively analyzed 81 eyes that underwent µLOT, in which three microhooks, the Sinskey hook, Tanito Micro-Hook-trabeculotomy-device (TMH), and Matsushita ed. TMH, were used. We collected the data from the medical records. We analyzed the success rates and risk factors. Failure was defined as the need for additional surgery for IOP reduction, loss of light perception, and IOP ≧22 mmHg and IOP reduction <20% (definition 1), IOP ≧17 mmHg and IOP reduction <20% (definition 2), IOP ≧15 mmHg and IOP reduction <25% (definition 3), or IOP ≧12 mmHg and IOP reduction <30% (definition 4) at two consecutive follow-up visits. RESULTS: Twenty-six eyes underwent µLOT using the Sinskey microhook (group S), 21 eyes using the TMH (group T), and 34 eyes using the Matsushita ed. TMH (group M). The mean postoperative IOP and IOP-lowering medication score decreased significantly. The respective success rates among groups S, T, and M did not differ significantly (definition 1, 65.4%, 61.9%, and 55.9%; definition 2, 42.3%, 47.6%, and 32.3%; definition 3, 15.4%, 28.6%, and 23.5%; definition 4, 0%, 9.5%, and 2.9%). In group S, the hyphema-related IOP spikes decreased within 2 weeks postoperatively, and in group M, the non-hyphema-related IOP spikes decreased significantly. CONCLUSION: The 1-year surgical outcomes and complications after µLOT did not differ significantly among the three microhooks. The differences in the microhook tips might be associated with postoperative transient IOP spikes.

Agent-based approach for elucidating the release from collective arrest of cell motion in corneal epithelial cell sheet.

Changes in cell fluidity have been observed in various cellular tissues and are strongly linked to biological phenomena such as self-organization. Recent studies suggested variety of mechanisms and factors, which are still being investigated. This study aimed to investigate changes in cell fluidity in multi-layered cell sheets, by exploring the collective arrest of cell motion and its release in cultures of corneal epithelial cells. We constructed mathematical models to simulate the behaviors of individual cells, including cell differentiation and time-dependent changes in cell-cell connections, which are defined by stochastic or kinetic rules. Changes in cell fluidity and cell sheet structures were expressed by simulating autonomous cell behaviors and interactions in tissues using an agent-based model. A single-cell level spatiotemporal analysis of cell state transition between migratable and non-migratable states revealed that the release from collective arrest of cell motion was initially triggered by a decreased ability to form cell-cell connections in the suprabasal layers, and was propagated by chain migration. Notably, the disruption of cell-cell connections and stratification occurred in the region of migratable state cells. Hence, a modeling approach that considers time-dependent changes in cell properties and behavior, and spatiotemporal analysis at the single-cell level can effectively delineate emergent phenomena arising from the complex interplay of cells.

Intensity-Modulated Radiation Therapy for Bilateral Choroidal Metastases Involving Macula and Optic Disc.

This case report discusses the case of a 76-year-old woman with choroidal metastasis from breast cancer who was treated with intensity-modulated radiation therapy (IMRT). Choroidal metastasis is a common ocular tumor, and the occurrence of this condition has increased due to improved diagnostic tools and longer survival of metastatic patients. IMRT is an innovative radiation therapy technique that reduces complications and improves the curative effect by concentrating radiation on the tumor while minimizing exposure to surrounding tissues. In this case, the patient had a history of breast cancer and was undergoing chemotherapy when she presented with vision loss and blurred vision. Imaging tests confirmed choroidal metastasis, and IMRT was performed under the guidance of a radiation oncologist. After treatment, the choroidal lesion dramatically reduced in size, and the patient's vision improved. The text concludes that radiation therapy, including IMRT, is becoming more common as a treatment for ocular metastasis to improve vision and preserve the eye. When choosing radiation therapy, it is essential to consider the size of the tumor and the impact on surrounding tissues. IMRT is an effective treatment that enables precise and concentrated irradiation of the tumor tissue while minimizing exposure to normal tissues.

Fungal dysbiosis and decreased tear mucin at the conjunctiva in patients with conjunctival mucosa-associated lymphoid tissue lymphoma.

OBJECTIVE: This study aimed to examine the differences in the fungal microbiome between patients with conjunctival mucosa-associated lymphoid tissue (MALT) and healthy controls using metagenomic analysis. METHODS AND ANALYSIS: This case-control study was conducted at Osaka University Hospital in Osaka, Japan, from April 2015 to March 2022. Twenty-five consecutive patients with conjunctival MALT lymphoma and 25 healthy volunteers were included. Metagenomic analysis using Internal Transcribed Spacer (ITS)1 deep sequencing and hierarchical clustering was performed to investigate differences in the fungal microbiome. To assess tear environmental change, we measured tear mucin concentrations using ELISA. RESULTS: Detailed analyses showed fungal dysbiosis and changes in ß-diversity within the conjunctiva of patients with conjunctival MALT lymphoma. Hierarchical clustering revealed that the participants could be divided into three clusters according to the Malassezia abundance: cluster I (Malassezia abundance above 70%), cluster II (Malassezia abundance 25%-70%) and cluster II (Malassezia abundance below 25%). Most patients were included in cluster I, whereas most of healthy controls were included in cluster III. The differences were significant. Tear mucin concentrations were significantly lower in patients with MALT compared with healthy controls. CONCLUSION: The metagenomic analysis using ITS1 deep sequencing was useful for identifying the differences in commensal fungi between patients with MALT lymphoma and healthy individuals. The increased prevalence of the Malassezia genus and the decreased levels of tear mucin can lead to an allergic response of the conjunctiva, resulting in the pathogenesis associated with conjunctival MALT lymphoma. Therefore, it may be beneficial to initiate treatment when a high abundance Malassezia is detected.

Ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier function.

Dry eye syndrome (DES) is a chronic ocular disease that induces epithelial damage to the cornea by decreasing tear production and quality. Adequate treatment options have not been established for severe DES such as Sjogren's syndrome due to complicated pathological conditions. To solve this problem, we focused on the conditioned medium of human adipose-derived mesenchymal stem cells (hAdMSC-CM), which have multiple therapeutic properties. Here, we showed that hAdMSC-CM suppressed Benzalkonium Chloride (BAC)-induced cytotoxicity and inflammation in human corneal epithelial cells (hCECs). In addition, hAdMSC-CM increased the expression level and regulated the localisation of barrier function-related components, and improved the BAC-induced barrier dysfunction in hCECs. RNA-seq analysis and pharmacological inhibition experiments revealed that the effects of hAdMSC-CM were associated with the TGFß and JAK-STAT signalling pathways. Moreover, in DES model rats with exorbital and intraorbital lacrimal gland excision, ocular instillation of hAdMSC-CM suppressed corneal epithelial damage by improving barrier dysfunction of the cornea. Thus, we demonstrated that hAdMSC-CM has multiple therapeutic properties associated with TGFß and JAK-STAT signalling pathways, and ocular instillation of hAdMSC-CM may serve as an innovative therapeutic agent for DES by improving corneal barrier function.

Long-term course with iris changes after trabeculectomy for uveitic glaucoma associated with iris mammillation: a case report.

BACKGROUND: Iris mammillation is a rare disease characterized by the distribution of multiple nodules on the iris surface. The course of uveitic glaucoma with iris mammillation has never been reported. CASE PRESENTATION: A 56-year-old woman, who presented with unilateral decreased vision, visited our hospital for treatment of uveitic glaucoma in the right eye. Multiple nodules were scattered over the iris surface in that eye. This case was diagnosed as iris mammillation on clinical findings. After excluding malignant tumors such as melanoma, trabeculectomy was performed. The resected iris had no pathologically malignant findings. The iris nodules evolved to a sand-like appearance, and the intraocular pressure remained stable without recurrent inflammation 7 years after trabeculectomy. CONCLUSIONS: In a case of unilateral uveitic glaucoma with iris mammillation, filtration surgery was performed after excluding the presence of a malignancy, and the long-term postoperative course has been stable.

Idiopathic Multicentric Castleman Disease Presenting With Hypertensive Choroidopathy: A Case Report.

Castleman disease (CD) is a lymphoproliferative disorder and rarely affects ocular tissue. This study aimed to report a case of hypertensive choroidopathy in a patient with Castleman's disease associated with malignant hypertension. A 39-year-old man visited his local physician with fever, systemic edema, and multiple lymphadenopathies. An inguinal lymph node biopsy indicated CD. One month after the biopsy, the patient noted a blurring of vision. At the time of the initial examination at our hospital, his best-corrected visual acuity (BCVA) was 20/20 in both eyes but there were bilateral multiple Elschnig spots and sprinter hemorrhage at the fundus. Swept-source optical coherence tomography showed intra-retinal fluid, and serous retinal detachment (SRD). Fluorescein angiography revealed multiple punctate hyper fluorescences and indocyanine green angiography showed choroidopathy with increased vascular permeability. A general examination revealed symptoms of cardiac failure and multiple lymphadenopathies. Malignant hypertension with acute glomerulonephritis was diagnosed after a renal biopsy. After antihypertensive treatment, his blood pressure (BP) improved, and the SRD and choroidopathy promptly resolved. Presently, the patient is being followed up without complications. We report a case of hypertensive choroidopathy in a patient with CD associated with malignant hypertension. As a severe elevation in BP can damage choroidal vasculature and lead to vision loss, careful observation and active treatment are necessary.

Clinical Trial of Autologous Cultivated Limbal Epithelial Cell Sheet Transplantation for Patients with Limbal Stem Cell Deficiency.

PURPOSE: To confirm the efficacy and safety of Good Manufacturing Practice (GMP)-compliant autologous cultivated limbal epithelial cell sheets in government-controlled clinical trials that adhered to Good Clinical Practice stipulations for patients with unilateral limbal stem cell deficiency (LSCD). DESIGN: A prospective, multicenter, open-label, uncontrolled, single-arm clinical trial. PARTICIPANTS: Ten consecutive eyes of 10 patients with unilateral LSCD were followed for 2 years after surgery. Preoperative LSCD stage was IIB in 4 eyes and III in 6 eyes. METHODS: A limbal tissue biopsy was obtained from the healthy eye, after which limbal stem cells were dissociated and cultivated on temperature-responsive culture surfaces. All cell sheets were fabricated in a GMP-grade facility under established standard operating procedures. Cell sheets were evaluated using defined shipment criteria before transplantation, and only those that met the criteria were used. The cell sheet was transplanted onto each of the patients' diseased eye after removing the conjunctival scar tissue that covered the corneal surface. The severity of LSCD was determined according to a staging method agreed on by global consensus, with eyes evaluated as being in stages IA-C representing successful corneal epithelial reconstruction. Diagnosis and staging of LSCD were determined by the trial's Eligibility Judgment Committee and Effect Assessment Committee using slit-lamp photographs including fluorescein staining. Both committees comprised 2 or 3 third-party cornea specialists, who were provided with information anonymously and randomly. MAIN OUTCOME MEASURE: Corneal epithelial reconstruction rate was the primary end point. RESULTS: Corneal epithelial reconstruction was successful in 6 of 10 eyes (60%) 1 year postoperatively and was significantly higher than the 15% clinically significant efficacy rate achieved by allogeneic limbal transplantation. The reconstruction rate was 70% of eyes 2 years postoperatively. Additionally, improvements in visual acuity were noted in 50% and 60% of eyes at 1 and 2 years, respectively. No clinically significant transplantation-related adverse events were observed. CONCLUSIONS: The efficacy and safety of cultivated limbal epithelial cell sheet transplantation were thus confirmed, and the cell sheet, named "Nepic," is now approved as a cellular and tissue-based product in Japan. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Embedding Technique versus Conventional Internal Limiting Membrane Peeling for Lamellar Macular Holes with Epiretinal Proliferation.

PURPOSE: To examine the outcomes of pars plana vitrectomy (PPV) with lamellar hole-associated epiretinal proliferation (LHEP) embedding and conventional internal limiting membrane (ILM) peeling for lamellar macular holes (LMHs) with LHEP. DESIGN: Retrospective observational study. SUBJECTS: Forty eyes of 39 consecutive patients with LMHs and LHEP who underwent 3-port PPV with a minimum follow-up of 3 months. METHODS: We compared the results of eyes that underwent PPV with LHEP embedding and ILM peeling (group E) with those of eyes that underwent PPV with ILM peeling only (group I) from September 2010 to September 2021. We confirmed whether the LHEP was embedded using postoperative OCT in all the cases. MAIN OUTCOME MEASURES: Postoperative best-corrected visual acuity (BCVA) and the development of macular holes (MHs) were assessed. RESULTS: The mean patient age was 73.3 years. The mean follow-up duration was 23.1 months. There were 23 and 17 eyes in groups E and I, respectively. Preoperative BCVA (P = 0.774) and central retinal thickness (CRT) (P = 0.800) did not differ significantly between the 2 groups. The final BCVA in group E was better than that in group I (P = 0.059). The final CRT in group E was thicker than that in group I (P < 0.001). Postoperatively, a significant improvement in BCVA was observed in group E at 3 months (P = 0.001) and at the final visit (P < 0.001). None of the eyes in group E developed postoperative MHs, whereas 5 eyes in group I developed postoperative MHs. CONCLUSIONS: Pars plana vitrectomy using the LHEP embedding technique improved visual acuity significantly and yielded better anatomic outcomes than those with PPV using conventional ILM peeling; MH formation did not occur. Embedding LHEP is more effective than conventional surgical procedures for LMHs.

Simultaneous intravitreal aflibercept and gas injections for submacular hemorrhage secondary to polypoidal choroidal vasculopathy.

PURPOSE: To investigate the outcomes of intravitreal aflibercept and gas injections for submacular hemorrhage (SMH) associated with polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively reviewed the medical records of 22 eyes with SMH secondary to PCV that underwent intravitreal aflibercept and 100% perfluoropropane (0.3-0.5 mL) followed by 3-day prone positioning from August 2013 through November 2020. The primary outcome measure was best-corrected visual acuity (BCVA) at 12 months. RESULTS: The average SMH size was 13.0 ± 9.7 (range, 2.0-37.8) disc diameter. The complete, partial, and no displacement of the SMH was observed in 8 (36%) eyes, 9 (41%) eyes, and 5 (23%) eyes, respectively. The BCVA (logarithm of the minimum angle of resolution) continuously improved significantly from 0.81 ± 0.41 (Snellen equivalent, 20/125) at baseline to 0.48 ± 0.44 (20/60), 0.33 ± 0.39 (20/43), and 0.28 ± 0.45 (20/38), at 3, 6, and 12 months, respectively (P = 0.01 for 3 months; P < 0.001 for 6 and 12 months). The BCVA improved by 3 or more lines in 14 eyes (64%). Two eyes (9%) developed visually significant vitreous hemorrhage, and 1 (5%) eye developed rhegmatogenous retinal detachment; all were successfully treated with vitrectomy. The better BCVA at 12 months tended to be associated with lower height of the SMH at baseline (R2 = 0.171, P = 0.056) and a greater displacement of SMH (R2 = 0.244, P = 0.069). Worse BCVA at 12 months was associated with anticoagulant medication (P < 0.001). CONCLUSIONS: Intravitreal aflibercept and gas injections are effective and relatively safe for SMH associated with PCV, resulting in significant visual improvement.

Barium-induced toxic anterior segment syndrome.

Toxic anterior segment syndrome (TASS) is a rapid-onset inflammation of the eye following uneventful ocular surgery. We report a case of TASS following Baerveldt glaucoma implant (BGI) surgery. Inductively coupled plasma-mass spectrometry (ICP-MS) identified barium in the eye and in the eluate from the bleb of the BGI. We attribute TASS in our patient to the dissolution of barium from the BGI and its entry into the eye, where it causes severe inflammation.