Exploring role of microbatteries in enhancing sustainability and functionality of implantable biosensors and bioelectronics.

Microbatteries are emerging as a sustainable, miniaturized power source, crucial for implantable biomedical devices. Their significance lies in offering high energy density, longevity, and rechargeability, facilitating uninterrupted health monitoring and treatment within the body. The review delves into the development of microbatteries, emphasizing their miniaturization and biocompatibility, crucial for long-term, safe in-vivo use. It examines cutting-edge manufacturing techniques like physical and chemical vapor deposition, and atomic layer deposition, essential for the precision manufacture of the microbatteries. The paper contrasts primary and secondary batteries, highlighting the advantages of zinc-ion and magnesium-ion batteries for enhanced stability and reduced reactivity. It also explores biodegradable batteries, potentially obviating the need for surgical extraction post-use. The integration of microbatteries into diagnostic and therapeutic devices is also discussed, illustrating how they enhance the efficacy and sustainability of implantable biosensors and bioelectronics.

Distribution of Neurofilament in Peeled Internal Limiting Membrane.

BACKGROUND AND OBJECTIVE: The aim was to study the distribution of neurofilament in peeled internal limiting membrane (ILM). PATIENTS AND METHODS: Prospective case study. Vitrectomy and ILM peeling were performed in patients with epiretinal membrane and macular hole. ILM flap specimens were obtained as one disc area size from five locations. Immunofluorescent staining was performed with an antineurofilament heavy antibody. Using a confocal microscope, retinal cell debris density was studied using the ImageJ program. RESULTS: Percent of stained neurofilament was 1.58 ± 1.14% in total (2.45 ± 1.37% in extranasal, 1.97 ± 0.75% in extratemporal, 1.93 ± 1.26% in juxta-nasal, 0.89 ± 0.69% in fovea, and 0.63 ± 0.46% in juxtatemporal). The Kruskal-Wallis test revealed significant differences among groups (P < 0.05). Bonferroni post hoc analysis only confirmed significant difference between juxtatemporal and extranasal groups (P < 0.05). CONCLUSIONS: In peeled ILM flap, neurofilaments are rarely detected in the juxtatemporal area. However, they are frequently detected in the extranasal area. [Ophthalmic Surg Lasers Imaging Retina 2023;54:643-648.].

Effects of Subcutaneous Methotrexate in Patients with Refractory Uveitis and Chorioretinitis.

PURPOSE: Methotrexate (MTX) is an immunosuppressive agent used to treat noninfectious inflammatory eye conditions and is generally administered orally for ocular inflammatory diseases. When used in rheumatological diseases, subcutaneous administration has been reported to show higher efficacy than oral administration. Therefore, this study aimed to evaluate the effect of subcutaneous MTX in patients with refractory uveitis or choroiditis who did not respond to other immunosuppressive agents. METHODS: A retrospective case series study was performed between January and December 2018. Patients with uveitis or chorioretinitis who showed little to no treatment response for 6 months or more with conventional immunosuppressive agents were treated with MTX, administered subcutaneously. After 6 months of treatment, patients were evaluated to determine whether complete suppression of inflammation sustained for ≥28 days was achieved in both eyes and whether improvement can be confirmed by fluorescein angiography (FAG). RESULTS: Subcutaneous MTX treatment was performed on 18 patients: 11 had intermediate uveitis and seven had posterior uveitis. In the intermediate uveitis patient group, five patients (50% of the group excluding one patient who dropped out) showed improvement in FAG and three patients (30%) showed complete suppression of inflammation. In the posterior uveitis group, two out of seven patients (excluding two patients who dropped out) showed an improvement, two patients in the group showed little change, and one patient showed aggravation of FAG findings. CONCLUSIONS: The study confirmed that in patients with uveitis or chorioretinitis who had a refractory response to treatment with other immunosuppressive agents, subcutaneous MTX showed improved treatment efficacy.

Effects of Subcutaneous Methotrexate in Patients with Refractory Uveitis and Chorioretinitis

Purpose@#Methotrexate (MTX) is an immunosuppressive agent used to treat noninfectious inflammatory eye conditions and is generally administered orally for ocular inflammatory diseases. When used in rheumatological diseases, subcutaneous administration has been reported to show higher efficacy than oral administration. Therefore, this study aimed to evaluate the effect of subcutaneous MTX in patients with refractory uveitis or choroiditis who did not respond to other immunosuppressive agents. @*Methods@#A retrospective case series study was performed between January and December 2018. Patients with uveitis or chorioretinitis who showed little to no treatment response for 6 months or more with conventional immunosuppressive agents were treated with MTX, administered subcutaneously. After 6 months of treatment, patients were evaluated to determine whether complete suppression of inflammation sustained for ≥28 days was achieved in both eyes and whether improvement can be confirmed by fluorescein angiography (FAG). @*Results@#Subcutaneous MTX treatment was performed on 18 patients: 11 had intermediate uveitis and seven had posterior uveitis. In the intermediate uveitis patient group, five patients (50% of the group excluding one patient who dropped out) showed improvement in FAG and three patients (30%) showed complete suppression of inflammation. In the posterior uveitis group, two out of seven patients (excluding two patients who dropped out) showed an improvement, two patients in the group showed little change, and one patient showed aggravation of FAG findings. @*Conclusions@#The study confirmed that in patients with uveitis or chorioretinitis who had a refractory response to treatment with other immunosuppressive agents, subcutaneous MTX showed improved treatment efficacy.

Prevalence and Progression of Stage 0 Macular Hole in Fellow Eyes of Patients with Idiopathic Full-thickness Macular Hole.

PURPOSE: To assess the prevalence and progression of a stage 0 macular hole in the fellow eye of patients with an idiopathic full-thickness macular hole. METHODS: The fellow eyes of 189 patients who underwent idiopathic full-thickness macular hole surgery were examined by biomicroscopy and spectral domain-optical coherence tomography (SD-OCT). A subset of 21 fellow eyes with a stage 0 macular hole was observed. Changes in the macular hole were evaluated by biomicroscopy and SD-OCT for an average of 29 months. RESULTS: Among the 21 eyes, 15 showed no change in perifoveal vitreous detachment (71.4%). Two eyes (9.5%) developed complete vitreofoveal separation, and one of the two developed a separation after progression to stage 1A. Among 21 eyes, 5 (23.8%) developed above stage 1A, and one of the five progressed to stage 1B after five years, which was successfully treated with vitrectomy and gas tamponade. CONCLUSIONS: Perifoveal vitreous detachment in the fellow eye on SD-OCT, defined as a stage 0 macular hole, occurred at an earlier phase than stage 1A macular holes and may progress to an advanced stage. Therefore, patients who undergo macular hole surgery and have a stage 0 macular hole or perifoveal vitreous detachment in the fellow eye should be followed closely.

One-year outcomes of fixed-dosing Aflibercept therapy for pre treated and naive polypoidal choroidal vasculopathy patient.

BACKGROUND: Polypoidal choroidal vasculopathy (PCV) is a type of age-related macular degeneration that can cause permanent vision loss. The purpose of this paper was to report the one-year outcomes of fixed-dosing aflibercept therapy for the treatment of PCV. METHODS: This was a prospective, single-arm, interventional case series study of 25 PCV patients; 12 pre-treated and 13 treatment-naïve patients. The patients were treated and monitored for 12 months. Each patient was administered with an aflibercept (2.0 mg) injection every month for the first 3 months (the loading phase), and thereafter, once every 2 months. At every follow-up visit, best-corrected visual acuity (BCVA) test, fundus examination, and optical coherence tomography for measuring the central subfield macular thickness (CSMT) were performed. Fluorescein and indocyanine green angiography were conducted at baseline and at 4 and 12 months. RESULTS: After 12 months of aflibercept therapy, the mean BCVA of the patients significantly improved from 65.48 letters at baseline to 69.91 letters (p=0.001), and the CSMT significantly decreased from 406.92 um at baseline to 276.12 um (p< 0.001). Additionally, ten patients (40%) showed complete polyp regression. The treatment-naïve patients showed a statistically significant improvement in BCVA from 66.58 letters at baseline to 76.36 letters at 12 months, and a significant decrease in CSMT, from 462 to 243 um. In the pre-treated group, there was no change in BCVA (64.46 letters), and the decrease in CSMT from 356.08 to 303.69 um was not statistically significant. CONCLUSIONS: The fixed-dosing aflibercept regimen is effective for treating patients with PCV and is more effective in treatment-naïve patients than in pre-treated patients. TRIAL REGISTRATION: Clinical Research Information Service (CRiS), Republic of Korea. Identifer: KCT0005798, Registered: Jan 20, 2021. Retrospectively registered, URL: https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=18546.

Clinical outcomes of combined pars plana vitrectomy and scleral fixation of the intraocular lens with a suspension bridge method in eyes with aphakia or insufficient capsular support.

PURPOSE: To describe a modified technique of scleral fixation for intraocular lens (IOL) implantation and report the clinical outcomes of combined pars plana vitrectomy and scleral IOL fixation using the suspension bridge method. METHODS: This retrospective case series included 57 eyes (56 patients) of aphakia or phakic and pseudophakic eyes with insufficient capsular support that underwent IOL implantation or dislocated IOL repositioning with scleral fixation using the 'suspension bridge' method by a single surgeon between 1 July 2010 and 1 March 2019. Preoperative status, changes in visual acuity, refractive outcomes as spherical equivalent and related complications were assessed with a minimum follow-up of 3 months. RESULTS: The mean follow-up period was 25.5 ± 25.4 months. Preoperative visual acuity (logarithm of the minimum angle of resolution) was 1.32 ± 0.68 (20/400 Snellen), and it significantly improved to 0.80 ± 0.53 (20/125), 0.59 ± 0.56 (20/80) and 0.24 ± 0.37 (20/35) at 1 week, 1 month and 3 months, respectively (p < 0.001). Postoperative complications included corneal wound dehiscence (n = 1), vitreous incarceration (n = 1), optic-iris capture (n = 6) and cystoid macular oedema (n = 1). The above-mentioned complications were successfully corrected with simple procedures. However, one case of IOL dislocation required reoperation. CONCLUSION: The modified technique of the suspension bridge method precludes the need for a scleral flap, with the advantage of easy adjustment of the IOL position. It is a simple and feasible technique with good surgical results and low complication rates.

Prevalence and Progression of Stage 0 Macular Hole in Fellow Eyes of Patients with Idiopathic Full-thickness Macular Hole

Purpose@#To assess the prevalence and progression of a stage 0 macular hole in the fellow eye of patients with an idiopathic full-thickness macular hole. @*Methods@#The fellow eyes of 189 patients who underwent idiopathic full-thickness macular hole surgery were examined by biomicroscopy and spectral domain-optical coherence tomography (SD-OCT). A subset of 21 fellow eyes with a stage 0 macular hole was observed. Changes in the macular hole were evaluated by biomicroscopy and SD-OCT for an average of 29 months. @*Results@#Among the 21 eyes, 15 showed no change in perifoveal vitreous detachment (71.4%). Two eyes (9.5%) developed complete vitreofoveal separation, and one of the two developed a separation after progression to stage 1A. Among 21 eyes, 5 (23.8%) developed above stage 1A, and one of the five progressed to stage 1B after five years, which was successfully treated with vitrectomy and gas tamponade. @*Conclusions@#Perifoveal vitreous detachment in the fellow eye on SD-OCT, defined as a stage 0 macular hole, occurred at an earlier phase than stage 1A macular holes and may progress to an advanced stage. Therefore, patients who undergo macular hole surgery and have a stage 0 macular hole or perifoveal vitreous detachment in the fellow eye should be followed closely.

Prevalence and Progression of Stage 0 Macular Hole in Fellow Eyes of Patients with Idiopathic Full-thickness Macular Hole

Purpose@#To assess the prevalence and progression of a stage 0 macular hole in the fellow eye of patients with an idiopathic full-thickness macular hole. @*Methods@#The fellow eyes of 189 patients who underwent idiopathic full-thickness macular hole surgery were examined by biomicroscopy and spectral domain-optical coherence tomography (SD-OCT). A subset of 21 fellow eyes with a stage 0 macular hole was observed. Changes in the macular hole were evaluated by biomicroscopy and SD-OCT for an average of 29 months. @*Results@#Among the 21 eyes, 15 showed no change in perifoveal vitreous detachment (71.4%). Two eyes (9.5%) developed complete vitreofoveal separation, and one of the two developed a separation after progression to stage 1A. Among 21 eyes, 5 (23.8%) developed above stage 1A, and one of the five progressed to stage 1B after five years, which was successfully treated with vitrectomy and gas tamponade. @*Conclusions@#Perifoveal vitreous detachment in the fellow eye on SD-OCT, defined as a stage 0 macular hole, occurred at an earlier phase than stage 1A macular holes and may progress to an advanced stage. Therefore, patients who undergo macular hole surgery and have a stage 0 macular hole or perifoveal vitreous detachment in the fellow eye should be followed closely.

Novel Findings of Polypoidal Choroidal Vasculopathy via Optical Coherence Tomography Angiography.

PURPOSE: To introduce novel findings of polypoidal choroidal vasculopathy (PCV) via optical coherence tomography angiography (OCTA). METHODS: This study is a retrospective chart review of 16 patients (16 eyes) with PCV. OCTA (Avanti RTVue XR) findings were evaluated and selected for analysis after agreement by two retina specialists . RESULTS: Twenty one polyps in 16 eyes (16 patients) with PCV were included in this study. The mean patient age was 67 years (13 men and three women). The shape of polypoidal lesions on OCTA at initial were halo (five polyps), rosette (seven polyps), and vascular network (nine polyps). Eight months after anti-vascular endothelial growth factor treatment, in a total of four eyes, seven polyps could be followed up completely, the two halo type polypoidal lesions changed to rosette and vascular network type. The lesions of three rosette and two vascular network type lesions did not change in shape. In addition, the size of the polypoidal lesions (one among two halo types, two among three rosette types, and two among two vascular network types) decreased, but one halo type did not change and one rosette type increased in size on OCTA. CONCLUSIONS: En-face OCTA enabled us to categorize novel types of PCV with polypoidal lesions.

Short-duration multiple-session subthreshold micropulse yellow laser (577 nm) for chronic central serous chorioretinopathy: results at 3 years.

OBJECTIVES: To review the 3-year follow-up results of subthreshold micropulse yellow laser (SMYL) delivered by a short-duration multiple-session method for treatment of chronic central serous chorioretinopathy (CSC). METHODS: A total of 27 eyes from 27 patients with chronic CSC available for 3 years of follow-up were enrolled in this retrospective and interventional study. Patients were treated with 577-nm SMYL photocoagulation at a 15% duty cycle over multiple sessions, with low power ranging from 200 to 400 mW that was increased in 100 mW increments according to resolution of subretinal fluid at monthly follow-up. Laser titration was not performed. A treatment duration of 20 ms rather than the conventional duration (100-300 ms) was applied over the area of retinal pigment epithelium leakage and all areas of serous retinal detachment, including the fovea. RESULTS: The mean follow-up period was 3.7 ± 0.8 years (range, 3-6 years). A total of 22 out of 27 eyes (81.5%) including six cases of recurrence during the follow-up period exhibited complete resolution of subretinal detachment at final follow-up, whereas only five eyes (15.5%) had either a partial or null response to SMYL treatment. The baseline best-corrected visual acuity was 0.26 ± 0.24 logarithm of the minimum angle of resolution (logMAR), which was improved to 0.08 ± 0.15 logMAR at 1-year (p = 0.005) and 3-year (p = 0.01) follow-up. The central macular thickness at baseline was 389.6 ± 103.4 µm, which was changed to 197.2 ± 40.0 µm (p < 0.001) at 1-year follow-up, 196.4 ± 40.2 µm (p < 0.001) at 3-year follow-up. CONCLUSION: Short-duration multiple-session SMYL therapy may be effective for long-term treatment of chronic CSC.

Novel Findings of Polypoidal Choroidal Vasculopathy via Optical Coherence Tomography Angiography

PURPOSE: To introduce novel findings of polypoidal choroidal vasculopathy (PCV) via optical coherence tomography angiography (OCTA) METHODS: This study is a retrospective chart review of 16 patients (16 eyes) with PCV. OCTA (Avanti RTVue XR) findings were evaluated and selected for analysis after agreement by two retina specialists . RESULTS: Twenty one polyps in 16 eyes (16 patients) with PCV were included in this study. The mean patient age was 67 years (13 men and three women). The shape of polypoidal lesions on OCTA at initial were halo (five polyps), rosette (seven polyps), and vascular network (nine polyps). Eight months after anti-vascular endothelial growth factor treatment, in a total of four eyes, seven polyps could be followed up completely, the two halo type polypoidal lesions changed to rosette and vascular network type. The lesions of three rosette and two vascular network type lesions did not change in shape. In addition, the size of the polypoidal lesions (one among two halo types, two among three rosette types, and two among two vascular network types) decreased, but one halo type did not change and one rosette type increased in size on OCTA. CONCLUSIONS: En-face OCTA enabled us to categorize novel types of PCV with polypoidal lesions.

EPIRETINAL MEMBRANE FORMATION AFTER INTRAVITREAL AUTOLOGOUS STEM CELL IMPLANTATION IN A RETINITIS PIGMENTOSA PATIENT.

METHODS: A retrospective case report of a retinitis pigmentosa patient who underwent vitrectomy for epiretinal membrane after intravitreal autologous stem cell implantation. RESULTS: A 71-year-old female RP patient came to our clinic for ophthalmic evaluation after intravitreal autologous stem cell injection. Four months ago, she underwent intravitreal autologous stem cell injection for both eyes at another hospital. New thick epiretinal membrane (ERM) with extensive macular pucker was found on her left eye. She underwent pars plana vitrectomy and membranectomy. After biopsy, many CD34-positive stem cells were detected in ERM specimen. CONCLUSION: This is the first report of ERM formation following intravitreal autologous stem cells injection. CD34-positive stem cells were detected in a human eye at 4 months after injection. Further studies are needed to determine how stem cells caused ERM and how long they would stay in the eye.

High Dose Intravitreal Bevacizumab for Refractory Pigment Epithelial Detachment in Age-related Macular Degeneration.

PURPOSE: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is the first choice of treatment for age-related macular degeneration. However, quite a few eyes treated using conventional dose anti-VEGF (CDAV) have persistent pigment epithelial detachment (PED) on optical coherence tomography. This study investigated the efficacy and safety of high dose anti-VEGF (HDAV) for refractory PED. METHODS: In this retrospective study, 31 eyes of neovascular age-related macular degeneration patients with persistent PED findings despite six or more intravitreal injections of CDAV (bevacizumab 1.25 mg or ranibizumab 2.5 mg) were analyzed. Changes in visual outcome, central foveal thickness, and PED height were compared before and after HDAV (bevacizumab 5.0 mg) for these refractory PED cases. RESULTS: The mean age of patients was 67.7 years. The number of CDAV injections was 12.1. The number of HDAV injections was 3.39. Best-corrected visual acuity in logarithm of the minimum angle of resolution before and after HDAV was 0.49 and 0.41 (p < 0.001), respectively. Central foveal thickness before and after HDAV was 330.06 and 311.10 µm (p = 0.125), respectively. PED height before and after HDAV was 230.28 and 204.07 µm (p = 0.014), respectively. There were no serious adverse reactions in all the eyes. CONCLUSIONS: Increasing the dose of bevacizumab in refractory PED may be a possible treatment option.

Management of Acute Submacular Hemorrhage with Intravitreal Injection of Tenecteplase, Anti-vascular Endothelial Growth Factor and Gas.

PURPOSE: To evaluate the visual and anatomical outcomes for neovascular age-related macular degeneration with submacular hemorrhage after intravitreal injections of tenecteplase (TNK), anti-vascular endothelial growth factor (VEGF) and expansile gas. METHODS: This study was a retrospective clinical case series following 25 eyes of 25 patients. All patients received a triple injection using 0.05 mL TNK (50 µg), 0.05 mL anti-VEGF and 0.3 mL of perfluoropropane gas. Retreatment with anti-VEGF was performed as needed. Preoperative and postoperative best-corrected visual acuity and central retinal thickness were analyzed. RESULTS: The mean logarithm of the minimum angle of resolution of best-corrected visual acuity improved significantly from 1.09 ± 0.77 at baseline to 0.52 ± 0.60 at 12 months (p < 0.001). The mean central retinal thickness also improved significantly from 545 ± 156 at baseline to 266 ± 107 at 12 months (p < 0.001). A visual improvement of 0.3 logarithm of the minimum angle of resolution unit or more was achieved in 15 eyes (60%). During the 12 postoperative months, an average of 4.04 intravitreal anti-VEGF injections was applied. CONCLUSIONS: A triple injection of TNK, anti-VEGF, and a gas appears to be safe and effective for the treatment of submacular hemorrhage secondary to neovascular age-related macular degeneration.

Blood Vessel Maturation by Disintegrin in Oxygen-Induced Retinopathy.

PURPOSE: Although Arg-Gly-Asp (RGD) motif-containing disintegrins are associated with integrin inhibition and the activation of various biological processes, little is known about the role of RGD motif-containing disintegrin in vascular development and remodeling. We therefore investigated the role of RGD-containing disintegrin in vascular remodeling in oxygen-induced retinopathy (OIR) mouse model. MATERIALS AND METHODS: EGT022, an RGD-containing disintegrin originated from human a disintegrin and metalloproteinase 15 (ADAM15), was used to investigate the role of the disintegrin in vascular development in OIR mouse model. To analyze the functional effects of EGT022 on retinal vascular development, the immunohistochemistry on mouse retinas after fluorescein isothiocyanate (FITC) perfusion was conducted and the vessel integrity was examined using modified Mile's permeability assay. RESULTS: EGT022 was able to reduce overall retinopathy scores by 75%, indicating its efficacy in retinal microvessel maturation stimulation. Pericyte coverage was greatly stimulated by EGT022 treatment in OIR mouse model. EGT022 was also effective to significantly improve blood vessel integrity. CONCLUSIONS: RGD-containing disintegrin EGT022 stimulated vascular maturation in OIR mouse model. Experimental results suggest that EGT022 is useful for treatments to improve ischemia in nonproliferative diabetic retinopathy (NPDR), the early stage of diabetic retinopathy.

Optical coherence tomography angiography in patients with polypoidal choroidal vasculopathy.

PURPOSE: To report the characteristics of polypoidal choroidal vasculopathy (PCV) based on optical coherence tomography angiography (OCTA) results. METHOD: A retrospective, cross-sectional case series was conducted. Patients treated for PCV were evaluated with the OCTA system. The OCTA images of these patients were compared with those from indocyanine green angiography (ICGA). All eyes of consecutive patients with PCV were included. RESULTS: The mean age of the patients (five men and two women) was 67.86 ± 14.02 years. The mean number of anti-vascular endothelial growth factor injections was 10.43 ± 10.01. OCTA demonstrated branched vascular networks, which were detected by ICGA; however, polyps were not revealed consistently by OCTA. A total of 24 polyps were detected in seven eyes from seven patients by hyper-fluorescence on ICGA. However, only 12 polyps (50 %) were hyper-reflective on OCTA. CONCLUSION: PCV polyps were not detected as consistently by OCTA as by ICGA. This suggests that the polyps were detected differently by OCTA depending on blood flow in the polyp.

Retinal Detachment and Proliferative Vitreoretinopathy.

In normal eyes, retinal detachment (RD) occurs at a rate of approximately 5 per 100,000 people per year and the frequency of proliferative vitreoretinopathy (PVR) remains largely unchanged in primary RD, with the incidence ranging from 5.1 to 11.7%. PVR is the most common cause of failed repair of rhegmatogenous RD, and risk factors for PVR are related to several well-known pre-, intra-, and postoperative clinical situations. Current methods of surgical management of RD and PVR are pneumatic retinopexy, scleral buckling, and pars plana vitrectomy (PPV). Surgical success rates for PVR have improved as techniques and instruments of vitrectomy evolved. However, despite these advances, more than one fourth of initially successful cases results in redetachment due to recurrent vitreoretinal traction. Retinal pigment epithelial cells are the key factor in triggering PVR development. In addition, soluble mediators and the extracellular matrix components play a critical role in cellular events, including proliferation and tissue contraction which occur in PVR. Although PPV remains a critical component of the treatment in RD and PVR, ongoing efforts seek to identify adjuvant therapies that might inhibit PVR development. Recent studies have therefore been directed toward pharmacologic inhibition of cellular proliferation and membrane contraction with drugs such as daunorubicin, 5-fluorouracil, and heparin. More detailed understanding of the pathophysiology underlying PVR may lead to the development of effective prophylactic and/or adjunctive therapies. Further work is necessary to identify optimal adjunctive therapies for the management of RD and PVR.

Macular Edema after Gabapentin

No abstract available.