Inherited retinal degenerations (IRDs) are a diverse group of conditions that are often characterized by the loss of photoreceptors and blindness. Recent innovations in molecular biology and genomics have allowed us to identify the causative defects behind these dystrophies and to design therapeutics that target specific mechanisms of retinal disease. Recently, the FDA approved the first in vivo gene therapy for one of these hereditary blinding conditions. Current clinical trials are exploring new therapies that could provide treatment for a growing number of retinal dystrophies. While the field has had early success with gene augmentation strategies for treating retinal disease based on loss-of-function mutations, many novel approaches hold the promise of offering therapies that span the full spectrum of causative mutations and mechanisms. Here, we provide a comprehensive review of the approaches currently in development including a discussion of retinal neuroprotection, gene therapies (gene augmentation, gene editing, RNA modification, optogenetics), and regenerative stem or precursor cell-based therapies. Our review focuses on technologies that are being developed for clinical translation or are in active clinical trials and discusses the advantages and limitations for each approach.

Sector and pericentral are two rare, regional forms of retinitis pigmentosa (RP). While usually defined as stable or only very slowly progressing, the available literature to support this claim is limited. Additionally, few studies have analyzed the spectrum of disease within a particular genotype. We identified all cases (9 patients) with an autosomal dominant Rhodopsin variant previously associated with sector RP (RHO c.316G > A, p.Gly106Arg) at our institution. Clinical histories were reviewed, and testing included visual fields, multimodal imaging, and electroretinography. Patients demonstrated a broad phenotypic spectrum that spanned regional phenotypes from sector-like to pericentral RP, as well as generalized disease. We also present evidence of significant intrafamilial variability in regional phenotypes. Finally, we present the longest-reported follow-up for a patient with RHO-associated sector-like RP, showing progression from sectoral to pericentral disease over three decades. In the absence of comorbid macular disease, the long-term prognosis for central visual acuity is good. However, we found that significant progression of RHO p.Gly106Arg disease can occur over protracted periods, with impact on peripheral vision. Longitudinal widefield imaging and periodic ERG reassessment are likely to aid in monitoring disease progression.

Purpose. To report the successful treatment of a case of presumed infectious crystalline keratopathy with repeated intrastromal antibiotic injections in a cornea graft in the setting of severe ocular graft-vs.-host-disease (GVHD). Observations. A 62-year-old man with a history of ocular GVHD and tectonic penetrating keratoplasty (PK) for corneal melt from herpes zoster keratopathy developed presumed infectious crystalline keratopathy (ICK) in the corneal graft. Given the patients complicated ocular history, chronic immunosuppression and new cardiac comorbidities, a therapeutic PK would most likely fail. Efforts were then directed to rescue the graft with minimally invasive approaches. Two separate intrastromal injections of cefuroxime and moxifloxacin successfully treated his ICK. Conclusions and Importance. This case supports a role for repeated intrastromal antibiotic injections in patients with ICK refractory to topical antibiotic therapy, which might eliminate the need for therapeutic PK and preserve vision.

Purpose: To describe atypical peripapillary retinal changes and neuroimaging findings in a patient with Gordon Holmes syndrome associated with compound heterozygous PNPLA6 variants, expanding the ophthalmic phenotype of this rare disorder. Methods: A single case was reviewed. Results: A 31-year-old woman with Gordon Holmes syndrome was referred for ophthalmic evaluation. Fundus autofluorescence imaging demonstrated atrophic peripapillary retinal pigment epithelial changes without central chorioretinal atrophy, distinguishing it from the phenotype typically seen in Boucher–Neuhäuser syndrome. Magnetic resonance imaging (MRI) of the brain revealed cerebellar atrophy and marked bilateral T2 hyperintensities in the basis pontis. Over 8 years of follow-up, visual acuity remained stable, with mild progression of pigment epithelial changes. Conclusions: Gordon Holmes syndrome may present with atypical peripapillary retinal changes and mild pigmentary retinopathy without clinically significant visual loss. These previously unrecognized retinal findings, along with atypical MRI features, broaden the ophthalmologic and neuroimaging spectrum of PNPLA6 -related disorders. Recognition of these manifestations may help ophthalmologists diagnose such rare neurodegenerative conditions.

Purpose: To report a case of bilateral occlusive retinal vasculitis in a patient with autoimmunity. Methods: A case was analyzed and a literature review performed. Results: A 55-year-old woman with autoimmune diagnoses of Isaacs syndrome and inclusion body myositis (IBM) reported decreased vision for 3 months. A fundus examination showed peripheral intraretinal hemorrhages in the right eye and an inferotemporal subhyaloid hemorrhage with adjacent intraretinal hemorrhages and preretinal fibrosis in the left eye. Fluorescein angiography showed temporal peripheral leakage and capillary dropout in both eyes, consistent with occlusive vasculitis. Scatter laser treatment to peripheral areas of retinal nonperfusion was followed by an intravitreal bevacizumab injection. Four months later, vision had stabilized at 20/15 in both eyes and the peripheral leakage had resolved. Conclusions: This patient developed retinal vasculitis associated with the rare autoimmune neuromuscular disorders of Isaacs syndrome and IBM. An extensive workup showed the most plausible mechanism for the vasculitis was autoimmunity with a history of previously elevated antibodies levels associated with the antiphospholipid syndrome.