Novel therapeutics for Stargardt disease.

DESCRIPTION OF SITUATION: Stargardt disease, an inherited macular dystrophy caused by mutations in the ABCA4 gene encoding a retinal transporter protein, is the most prevalent form of macular degeneration in children. Patients with Stargardt disease develop severe vision loss within their first or second decades of life, which progresses to irreversible decreased visual acuity in almost all cases. Presently, there are no standard treatments for Stargardt disease. However, encouraging progress has been made in the development of innovative approaches to preventing vision loss in Stargardt patients. OBJECTIVE OF STUDY: Among the promising treatment candidates include ALK-001, fenretinide, and A1120 as pharmacological agents to modulate the visual cycle, StarGenTM as a vector for supplementation of a functional ABCA4 gene, and stem-cell transplantation of hESC-RPE cells for regeneration of the retinal pigment epithelium. This study aims to systematically review and summarize evidence concerning the most up-to-date developments in pharmacologic, gene, and stem-cell therapies as novel therapeutic strategies to improve vision for patients with Stargardt disease.

Novel Pharmacologic Candidates for Treatment of Primary Open-Angle Glaucoma.

Primary open-angle glaucoma (OAG) affects approximately 45 million people worldwide and more than 2.5 million people aged 40 years or older in the United States. Pharmacologic treatment for glaucoma is directed towards lowering intraocular pressure (IOP) to slow disease progression and delay visual field loss. Current medical treatment options for the lowering of IOP include the following classes of topical medications: beta-adrenergic antagonists, alpha-adrenergic agonists, cholinergic agonists, carbonic anhydrase inhibitors, and prostaglandin analogs. Issues with existing drugs include failure to achieve target IOP with monotherapy, drug-related side effects, and low patient compliance with multiple daily administration of eye drops. In recent years, the scientific and medical community has seen encouraging development of novel classes of drugs for primary OAG, the majority of which lower IOP by targeting the trabecular meshwork outflow pathway to increase aqueous humor outflow. Among the most promising new pharmacologic candidates are rho kinase inhibitors including ripasudil (K-115), netarsudil (AR-13324), and AMA0076; adenosine receptor agonists including trabodenoson (INO-8875); and modified prostaglandin analogs including latanoprostene bunod (LBN, BOL-303259-X) and ONO-9054. This study aims to systematically review and summarize the most recent developments in clinical trials for new pharmacologic options for the treatment of primary open-angle glaucoma.

Human Microbiota and Ophthalmic Disease.

The human ocular surface, consisting of the cornea and conjunctiva, is colonized by an expansive, diverse microbial community. Molecular-based methods, such as 16S rRNA sequencing, has allowed for more comprehensive and precise identification of the species composition of the ocular surface microbiota compared to traditional culture-based methods. Evidence suggests that the normal microbiota plays a protective immunological role in preventing the proliferation of pathogenic species and thus, alterations in the homeostatic microbiome may be linked to ophthalmic pathologies. Further investigation of the ocular surface microbiome, as well as the microbiome of other areas of the body such as the oral mucosa and gut, and their role in the pathophysiology of diseases is a significant, emerging field of research, and may someday enable the development of novel probiotic approaches for the treatment and prevention of ophthalmic diseases.

Contralateral Eye Involvement and Retinal Detachment in Patients with Cytomegalovirus Retinitis Treated with Intravitreous Ganciclovir.

Purpose: To determine the incidence of contralateral eye involvement and retinal detachment in HIV-infected patients with cytomegalovirus retinitis treated with repeated intravitreous ganciclovir.Methods: In a prospective cohort study in Northern Thailand, HIV-infected patients with cytomegalovirus retinitis were treated with antiretroviral therapy and intravitreous ganciclovir injections and followed for 3 months for contralateral cytomegalovirus retinitis and retinal detachment.Results: Of 49 participants with unilateral cytomegalovirus retinitis at enrollment, 7 developed contralateral eye involvement (4.8/100 person-months, 95% CI 1.9-9.8). Of 105 eyes without a retinal detachment at enrollment, 6 developed a retinal detachment (2.0/100 eye-months, 95% CI 0.7-4.3). Baseline clinical factors were not associated with the development of either outcome.Conclusion: Eyes treated with intravitreous ganciclovir experienced retinal detachment at a rate similar to other populations treated with systemic antivirals. The risk of contralateral eye involvement was relatively high during the first 3 months after initial diagnosis despite the institution of antiretroviral therapy.

Clinical Etiologies, Microbial Spectrum, Antibiotic Susceptibilities, and Visual Acuity Outcomes of Acute Endophthalmitis.

Purpose: The purpose of this study was to report the clinical etiologies, microbial spectrum, antibiotic resistance, and visual acuity (VA) outcomes associated with acute endophthalmitis. Methods: A retrospective chart review of patients with International Classification of Diseases (ICD)-9 and ICD-10 codes for endophthalmitis over a 6-year period (2011-2016) at a tertiary referral center was performed. The clinical records were reviewed to evaluate clinical etiologies, microbial spectrum, antibiotic susceptibilities and resistance, and visual outcomes. Results: Medical records of 94 patients treated for culture-proven endophthalmitis were reviewed. The etiologies of endophthalmitis were exogenous in 68.8% of cases and endogenous in 31.2% of cases. The most common inciting factors for exogenous endophthalmitis were progression of corneal ulcer and postoperative infection after cataract extraction. The microbial spectrum of causative organisms was dominated by coagulase-negative Staphylococcus (30.9%), followed by Staphylococcus aureus (23.4%). The most frequent fungal isolates were Candida species. Antibiotic susceptibilities of gram-positive bacteria ranged from 96.7% for vancomycin to 28.8% for penicillin G. Antibiotic susceptibilities of gram-negative bacteria were overall very high, with >90% susceptibility among isolated culture samples. Final VA outcomes of 20/400 or better were reported in 62.5% of patients. Conclusions: The study demonstrates that the most frequent clinical etiology of endophthalmitis was exogenous due to progression of corneal ulcer and postoperative infection after cataract extraction. The spectrum of pathogens causing endophthalmitis is composed of mainly Gram-positive organisms (particularly coagulase-negative Staphylococcus). VA was improved in the majority of patients after treatment for endophthalmitis.