黄斑ジストロフィー

PURPOSE: This pilot study investigates the efficacy of a liposomal ophthalmic solution containing cross-linked hyaluronic acid, trehalose, and stearylamine in reducing the occurrence of dry eye-like signs and symptoms in patients undergoing repeated intravitreal treatment. METHODS: Participants aged over 50 years old were randomly assigned to receive either standard therapy alone (Group 1) or standard therapy with additional eye drops (Group 2). Examinations included TBUT, Schirmer's test, fluorescein staining, the Ocular Surface Disease Index (OSDI), and the 5-item Dry Eye Questionnaire (DEQ-5) at baseline and day 15, with a 30-day telephone follow-up for OSDI reassessment. RESULTS: Ninety patients with age-related macular degeneration or other retinal diseases requiring anti-VEGF (vascular endothelial growth factor) treatment were enrolled in the study. In Group 1, which comprised 20 males and 25 females, DEQ-5 scores did not exhibit any significant change between V0 and V1 (10.89 ± 2.71 to 10.57 ± 2.60, p = 0.173), while Group 2, composed of 18 males and 27 females, demonstrated a considerable reduction in DEQ-5 values (9.28 ± 3.24 to 8.00 ± 3.64, p < 0.0001). OSDI scores in Group 1 showed no relevant change between V0 and V1 (p = 0.497), whereas in Group 2 they improved significantly (p < 0.0001). Additionally, Group 2 had notable enhancements in TBUT and Schirmer tests (p < 0.0001), while Group 1 experienced a significant decrease in TBUT values alone (p = 0.026). CONCLUSION: Chronic intravitreal therapy contributes to significant ocular surface impairment, which can be effectively mitigated by the administration of a tear substitute alongside the standard treatment.

PURPOSE: This study aimed to report the 10-year follow-up results of the first-in-human study of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) sheet transplantation, with a focus on long-term graft persistence assessed using multimodal imaging, including polarization-sensitive optical coherence tomography (PS-OCT)-based melanin evaluation. DESIGN: Follow-up of a single patient PARTICIPANT: A patient with neovascular age-related macular degeneration METHODS: Autologous iPSC-derived RPE sheets were transplanted into the subretinal space in 2014. MAIN OUTCOME MEASURES: Engraftment of the transplanted RPE sheet and preservation of the host retinal structure were evaluated using multimodal imaging, including color fundus photography, spectral-domain (SD)-OCT and PS-OCT, and near-infrared autofluorescence (NIRAF), throughout the post-transplantation period. RESULTS: The patient was aged 88 years at the 10-year post-transplantation follow-up. There was stable anatomic appearance of the persistent subretinal pigmentation on color fundus photography. SD-OCT revealed the preservation of the outer nuclear layer over the graft. Choroidal thickness analysis indicated sustained structural preservation beneath the graft. PS-OCT demonstrated persistent depolarization signals of the RPE layer, which were separated from the overlying retina and corresponded to the pigmented area observed on color fundus photography. The combination of high polarimetric entropy on PS-OCT and low-to-iso-autofluorescence on NIRAF further delineated the grafted area, distinguishing it from healthy and atrophic regions. CONCLUSIONS: Sustained preservation of the overlying neurosensory retina and underlying choroid, in conjunction with long-term pigment persistence, provides important evidence of the safety and structural stability of iPSC-based cell therapy. These findings support the potential of this approach for broader clinical application in regenerative medicine.

PURPOSE: To examine the safety of the epidermal growth factor (EGF) receptor antibody panitumumab intravitreally applied in patients with myopic macular degeneration (MMD) or neovascular age-related macular degeneration (AMD). METHODS: Patients with MMD stage 4 underwent repeated intravitreal panitumumab injections in escalating doses, and patients with neovascular AMD received combined intravitreal ranibizumab/panitumumab injections, with single ranibizumab injections applied in between. RESULTS: The study included 28 patients. In the first cohort, 11 highly myopic patients with MMD stage 4 (age: 66.8 ± 6.3 years) received intravitreal panitumumab injections in doses of 0.6 mg (4 eyes; 1 × 1 injection, 3 × 2 Injections), 1.2 mg (4 eyes; 1 × 1 injection; 2 × 2 injections; 1 × 3 injections) and 1.8 mg (3 eyes; 1 × 1 injection, 2 × 2 injections), respectively, in intervals of 3.6 ± 1.8 months (first to second injection), and 4.7 months (second to third injection). At 3.7 ± 0.4 years (median: 3.6 years; range: 3.5-4.7 years) after the first injection, ten patients were re-examined, with no change in axial length (30.6 ± 1.0 vs. 30.7 ± 1.3; p = 0.66). A second cohort included 17 eyes with neovascular AMD and receiving bimonthly combined panitumumab/ranibizumab (1.2 mg/0.5 mg) injections (mean: 2.4 ± 0.5 injections). The mean follow-up period was 11.0 ± 1.0 months (median: 11 months; range: 6-14 months). In none of the eyes of the first and second cohort, treatment-related systemic or intraocular adverse events were noted. Ocular side effects were hyposphagmata at the injection sites. Signs of intraocular inflammation were not detected in any eye. The morphology of the optic nerve head did not change significantly, nor did the IOP (14.5 ± 4.3 mmHg vs. 13.5 ± 1.5 mmHg; p = 0.30). CONCLUSIONS: Repeated intravitreal panitumumab applications in various doses, single or combined with ranibizumab, were not associated with severe ocular or systemic side effects.

Choroidal neovascular membranes (CNVM) are abnormal vascular complexes that can cause serious visual morbidity if untreated. They can be induced by the C1QTNF5 mutation, which disrupts retinal pigment epithelium (RPE) adhesion and leads to progressive sub-RPE deposit accumulation. Due to its overlapping clinical presentation with age-related macular degeneration (AMD), C1QTNF5-associated CNVM is often misdiagnosed. Early recognition of atypical CNVM clinical presentations is essential to prompt genetic testing and initiate personalized antivascular endothelial growth factor (anti-VEGF) therapy. We report a 57-year-old male with a history of pontine stroke and strabismus surgery who presented with bilateral submacular hemorrhages and visual distortion. Given the atypical bilateral presentation and absence of drusen, genetic testing was performed. A pathogenic C1QTNF5 mutation with a p. Asn22Lys variant was identified. Treatment was initiated with intravitreal bevacizumab (IVA) injection and switched to aflibercept (IVE). After 2 years of tailored injection intervals based on optical coherence tomography (OCT) and visual acuity, the patient achieved visual acuity of 20/25 in both eyes with complete or near-complete resolution of subretinal fluid. A pro re nata (PRN) protocol was then initiated, and vision remained stable at the 4-year follow-up. This case highlights the importance of considering inherited retinal disease in atypical CNVM presentations. Early diagnosis, genetic testing, and individualized, imaging-driven anti-VEGF therapy can lead to long-term stability and favorable visual outcomes in patients with C1QTNF5-associated CNVM. Although causality cannot be established from a single case, concurrent glaucoma findings support the need for comprehensive ocular surveillance in patients with C1QTNF5 mutations.