Retinal Prostheses: Engineering and Clinical Perspectives for Vision Restoration.

A retinal prosthesis, also known as a bionic eye, is a device that can be implanted to partially restore vision in patients with retinal diseases that have resulted in the loss of photoreceptors (e.g., age-related macular degeneration and retinitis pigmentosa). Recently, there have been major breakthroughs in retinal prosthesis technology, with the creation of numerous types of implants, including epiretinal, subretinal, and suprachoroidal sensors. These devices can stimulate the remaining cells in the retina with electric signals to create a visual sensation. A literature review of the pre-clinical and clinical studies published between 2017 and 2023 is conducted. This narrative review delves into the retinal anatomy, physiology, pathology, and principles underlying electronic retinal prostheses. Engineering aspects are explored, including electrode-retina alignment, electrode size and material, charge density, resolution limits, spatial selectivity, and bidirectional closed-loop systems. This article also discusses clinical aspects, focusing on safety, adverse events, visual function, outcomes, and the importance of rehabilitation programs. Moreover, there is ongoing debate over whether implantable retinal devices still offer a promising approach for the treatment of retinal diseases, considering the recent emergence of cell-based and gene-based therapies as well as optogenetics. This review compares retinal prostheses with these alternative therapies, providing a balanced perspective on their advantages and limitations. The recent advancements in retinal prosthesis technology are also outlined, emphasizing progress in engineering and the outlook of retinal prostheses. While acknowledging the challenges and complexities of the technology, this article highlights the significant potential of retinal prostheses for vision restoration in individuals with retinal diseases and calls for continued research and development to refine and enhance their performance, ultimately improving patient outcomes and quality of life.

Retinitis Pigmentosa: Novel Therapeutic Targets and Drug Development.

Retinitis pigmentosa (RP) is a heterogeneous group of hereditary diseases characterized by progressive degeneration of retinal photoreceptors leading to progressive visual decline. It is the most common type of inherited retinal dystrophy and has a high burden on both patients and society. This condition causes gradual loss of vision, with its typical manifestations including nyctalopia, concentric visual field loss, and ultimately bilateral central vision loss. It is one of the leading causes of visual disability and blindness in people under 60 years old and affects over 1.5 million people worldwide. There is currently no curative treatment for people with RP, and only a small group of patients with confirmed RPE65 mutations are eligible to receive the only gene therapy on the market: voretigene neparvovec. The current therapeutic armamentarium is limited to retinoids, vitamin A supplements, protection from sunlight, visual aids, and medical and surgical interventions to treat ophthalmic comorbidities, which only aim to slow down the progression of the disease. Considering such a limited therapeutic landscape, there is an urgent need for developing new and individualized therapeutic modalities targeting retinal degeneration. Although the heterogeneity of gene mutations involved in RP makes its target treatment development difficult, recent fundamental studies showed promising progress in elucidation of the photoreceptor degeneration mechanism. The discovery of novel molecule therapeutics that can selectively target specific receptors or specific pathways will serve as a solid foundation for advanced drug development. This article is a review of recent progress in novel treatment of RP focusing on preclinical stage fundamental research on molecular targets, which will serve as a starting point for advanced drug development. We will review the alterations in the molecular pathways involved in the development of RP, mainly those regarding endoplasmic reticulum (ER) stress and apoptotic pathways, maintenance of the redox balance, and genomic stability. We will then discuss the therapeutic approaches under development, such as gene and cell therapy, as well as the recent literature identifying novel potential drug targets for RP.

Hydrogels in Ophthalmology: Novel Strategies for Overcoming Therapeutic Challenges.

The human eye's intricate anatomical and physiological design necessitates tailored approaches for managing ocular diseases. Recent advancements in ophthalmology underscore the potential of hydrogels as a versatile therapeutic tool, owing to their biocompatibility, adaptability, and customizability. This review offers an exploration of hydrogel applications in ophthalmology over the past five years. Emphasis is placed on their role in optimized drug delivery for the posterior segment and advancements in intraocular lens technology. Hydrogels demonstrate the capacity for targeted, controlled, and sustained drug release in the posterior segment of the eye, potentially minimizing invasive interventions and enhancing patient outcomes. Furthermore, in intraocular lens domains, hydrogels showcase potential in post-operative drug delivery, disease sensing, and improved biocompatibility. However, while their promise is immense, most hydrogel-based studies remain preclinical, necessitating rigorous clinical evaluations. Patient-specific factors, potential complications, and the current nascent stage of research should inform their clinical application. In essence, the incorporation of hydrogels into ocular therapeutics represents a seminal convergence of material science and medicine, heralding advancements in patient-centric care within ophthalmology.

FOVEAL OUTER RETINAL HYPERREFLECTIVITY: A NOVEL OPTICAL COHERENCE TOMOGRAPHY FINDING IN IDIOPATHIC MULTIFOCAL CHOROIDITIS.

PURPOSE: To describe three patients with idiopathic multifocal choroiditis (MFC) who showed foci of foveal outer retinal hyperreflectivity on optical coherence tomography. METHODS: Retrospective review of electronic health records and multimodal imaging from three patients with MFC. RESULTS: Three consecutive white patients with MFC (two male and one female) presented with unilateral foveal outer retinal hyperreflectivity in the eye with active MFC. In all cases, the lesions persisted for at least 1 month. Optical coherence tomography demonstrated finger-like projections of hyperreflectivity extending from the retinal pigment epithelium and through disrupted interdigitation and ellipsoid zones into the outer nuclear layer, with some aspects of the lesions reaching the inner limiting membrane. Visual recovery varied in the three affected eyes. CONCLUSION: Foveal outer retinal hyperreflectivity is a novel optical coherence tomography finding in eyes with active MFC. Additional studies will be required to address the prevalence and prognostic importance of foveal outer retinal hyperreflectivity.

PARACENTRAL ACUTE MIDDLE MACULOPATHY ASSOCIATED WITH IDIOPATHIC INTRACRANIAL HYPERTENSION.

PURPOSE: Paracentral acute middle maculopathy (PAMM) is a recently identified clinical entity with numerous retinal vascular and systemic associations. To our knowledge, this is the first reported case of PAMM associated with idiopathic intracranial hypertension. METHODS: A case is presented with multimodal imaging. RESULTS: A patient with idiopathic intracranial hypertension is found to have the characteristic clinical, spectral domain optical coherence tomography, and OCT angiography findings associated with PAMM. CONCLUSION: Paracentral acute middle maculopathy is believed to arise from a microvascular insult to the retinal deep capillary plexus. We add a previously undescribed association with idiopathic intracranial hypertension to the list of etiologies that can cause PAMM.

NOVEL APPROACH TO SCLERAL FIXATION OF A REPER INTRAOCULAR LENS AND ARTIFICIAL IRIS COMPLEX FOLLOWING PARS PLANA LENSECTOMY AND VITRECTOMY FOR ECTOPIA LENTIS AND CATARACT IN A PATIENT WITH ANIRIDIA AND NYSTAGMUS.

PURPOSE: Prosthetic iris devices have recently been used to improve cosmesis and reduce glare in aniridia. There is currently no consensus on which prosthetic iris device or which surgical approach is preferred for managing large iris defects. METHODS: A novel surgical approach with Gore-Tex polytetrafluoroethylene sutures was used to achieve scleral fixation of an intraocular lens and artificial iris complex in a 19-year-old Caucasian female patient with aniridia, nystagmus, cataracts, and ectopia lentis. RESULTS: Six weeks postoperatively, the intraocular lens-artificial iris complex remained well centered, and the vision in the left eye improved from 20/400 to 20/70. Two years after prosthetic iris device implantation, there have been no complications. CONCLUSION: This case demonstrates a promising proof-of-concept for long-term management of complicated aniridia cases using an intraocular lens and artificial iris complex prosthetic iris devices. Gore-Tex sutures may be preferable to conventional polypropylene sutures because of their improved durability.

Refractive, visual, and subjective quality of vision outcomes for very high myopia LASIK from - 10.00 to - 13.50 diopters.

BACKGROUND: To evaluate laser-assisted in situ keratomileusis (LASIK) outcomes, subjective quality of vision (QoV) and patient satisfaction in eyes with very high myopia (VHM) above - 10.00 diopters (D). METHODS: Consecutive myopic and myopic-astigmatism eyes with spherical equivalent (SEQ) ranging between - 10.00 to - 13.50 D underwent LASIK with the WaveLight® Allegretto Wave® Eye-Q 400 Hz excimer laser. Treatment accuracy, efficacy, safety, stability, cylinder vectors, and higher-order aberrations were evaluated, together with subjective QoV and night vision disturbances (NVDs). RESULTS: 114 eyes had a preoperative SEQ of - 11.02 ± 0.81 D, with a median follow-up of 24 months. A total of 72, 84, and 94% of eyes were within ± 0.50, ± 0.75 and ± 1.00 D of intended SEQ (R2 = 0.71). The efficacy index was 0.93 ± 0.20, with 51 and 81% of eyes achieving 20/20 and 20/25. The astigmatism correction index was 0.95 ± 0.33. The safety index was 1.05 ± 0.12. The average myopic regression was - 0.51 ± 0.38 D. Preoperative QoV scores improved significantly postoperatively (7.5 ± 0.8 vs. 9.1 ± 0.7; P <  0.001), with less NVDs (P <  0.001). Total, spherical and coma root mean square (RMS) postoperative ocular higher-order aberrations were 1.07 ± 0.34, 0.67 ± 0.25, and 0.70 ± 0.40 µm. CONCLUSIONS: Very high myopia LASIK between - 10.00 to - 13.50 D is safe and results in good visual outcomes, with high patient satisfaction and a significant improvement in patient-reported QoV after surgery. Appropriately selected patients within this very high myopia group can be included as LASIK candidates.

OPACIFICATION OF SCLERAL-SUTURED AKREOS AO60 INTRAOCULAR LENS AFTER VITRECTOMY WITH GAS TAMPONADE: CASE SERIES.

BACKGROUND/PURPOSE: We report the first two cases of postoperative opacification of scleral-sutured Akreos AO60 intraocular lens after vitrectomy with the gas tamponade. METHODS: Two patients with ectopia lentis underwent pars plana vitrectomy, pars plana lensectomy, and scleral fixation of an Akreos AO60 intraocular lens with Gore-Tex suture. Retinal breaks were noted during vitrectomy and consequently intravitreal gas tamponade was used after endolaser retinopexy. Postoperatively, both patients developed intraocular lens opacification but maintained excellent visual acuity; however, one patient developed bothersome though tolerable photophobia. CONCLUSION: Although still an excellent option for the management of surgical aphakia in the absence of capsular support, caution should be taken when using a hydrophilic secondary intraocular lens, such as Akreos AO60, during vitreoretinal surgery if gas is required.

IMMUNE RETINOPATHY ASSOCIATED WITH NIVOLUMAB ADMINISTRATION FOR METASTATIC NON-SMALL CELL LUNG CANCER.

PURPOSE: To present a novel case of immune retinopathy associated with nivolumab therapy for non-small cell lung cancer. METHODS: Retrospective chart review. RESULTS: A 64-year-old woman presented with photoreceptor injury evidenced by hypoautofluorescent and hyperautofluorescent patches on fundus autofluorescence, loss of the ellipsoid zone on optical coherence tomography, and dysfunction of the rods and cones on electroretinogram. She had a history of Stage IV lung adenocarcinoma, treated with nivolumab, a checkpoint inhibitor. Serology testing was negative for paraneoplastic antibody panel, antirecoverin and antienolase antibodies, but positive for antiretinal antibodies against 30-kDa (carbonic anhydrase II), 35-kDa (GADPH), 38-kDA, 58-kDa (PKM2), and 112-kDa proteins. Cessation of the medication and high-dose oral steroids resulted in resolution of her symptoms and stability of ocular findings. CONCLUSION: The checkpoint inhibitors, including nivolumab, have significant ocular side effects. All patients receiving nivolumab should undergo a baseline comprehensive eye examination and should be counseled to seek medical attention immediately if visual changes occur.

AUTOSOMAL RECESSIVE BESTROPHINOPATHY: MULTIMODAL IMAGING UPDATE.

BACKGROUND: Autosomal recessive bestrophinopathy is part of the diverse spectrum of retinal diseases caused by mutations in the BEST1 gene. METHODS: A case report. RESULTS: We present a case that highlights the classic retinal findings of autosomal recessive bestrophinopathy with an emphasis on modern multimodal imaging. CONCLUSION: We describe modern multimodal imaging in an individual with a BEST1 gene mutation and clinical findings consistent with an autosomal recessive bestrophinopathy.

COMBINING EXTERNAL NEEDLE DRAINAGE AND SCLERAL BUCKLING WITH VITRECTOMY FOR THE REPAIR OF BULLOUS RETINAL DETACHMENTS.

PURPOSE: To describe a technique of combined scleral buckle with external needle drainage and vitrectomy in the treatment of bullous exudative retinal detachment, schisis detachment, or bullous retinoschisis threatening the fovea. METHODS: A retrospective chart review of four eyes of four patients who underwent the procedure described. RESULTS: Four eyes of four patients who underwent combined scleral buckling with external needle drainage and vitrectomy by a single surgeon for a bullous exudative retinal detachment, schisis detachment, or bullous retinoschisis threatening the fovea were included in this series. All four patients were attached after a single surgical intervention. No patient developed complications from the external drainage. CONCLUSION: External needle drainage of bullous subretinal or intraschisis fluid in combination with vitrectomy is a successful technique for treating bullous exudative retinal detachments, schisis detachment, or foveal-threatening retinoschisis. The technique avoids many complications associated with conventional drainage procedures. Long-term results seem promising because of extended follow-up demonstrating sustained anatomical success with a single intervention.

TRANSTHYRETIN V30M FAMILIAL AMYLOIDOSIS PRESENTING AS ISOLATED RETINAL ANGIOPATHY.

PURPOSE: To describe a patient with confirmed transthyretin V30M form of familial amyloidosis who presented initially with isolated retinal angiopathy. METHODS: Retrospective chart review. RESULTS: A 66-year-old woman presented with bilateral retinal angiopathy. Extensive workup for an infectious, inflammatory, or hypercoagulable cause was unrevealing. The patient subsequently developed bilateral neovascularization of the optic nerve and iris complicated by recurrent vitreous hemorrhages, which were treated with intravitreal bevacizumab and panretinal photocoagulation. The development of cardiac and gastrointestinal symptoms 5 years after presentation led to tissue biopsies that revealed both Congo red staining and apple-green birefringence in polarized light, confirming the diagnosis of systemic amyloidosis. Sequencing of the transthyretin gene confirmed the patient to be heterozygous for the common amyloidogenic V30M mutation. CONCLUSION: The common transthyretin V30M form of familial amyloidotic polyneuropathy can rarely present with retinal angiopathy. Recurrent vitreous hemorrhages were treated successfully with intravitreal bevacizumab and panretinal photocoagulation.