Case report on a de novo variant in the X-linked PRPS1 gene presenting with retinal dystrophy, severe tremors, and ataxia in a female patient.

CASE SUMMARY: The patient is a 42-year-old female who presented with a de novo missense variant in the PRPS1 gene. Her phenotype includes asymmetric retinal dystrophy with sensory esotropia, congenital sensorineural hearing loss, neuropathy, and severe tremors with recent-onset ataxia. This contributes a new presentation of ophthalmic and neurological findings to the literature.

Pattern-reversal visual evoked potentials in prosthetic vision and simulated visual reduction.

OBJECTIVE: To quantitatively evaluate visual evoked potentials (VEPs) in prosthetic vision and simulated visual reduction. METHODS AND ANALYSIS: Four blind patients implanted with the Argus II retinal prosthesis and seven sighted controls participated. VEPs were recorded with pattern-reversal stimuli (2 cycles of a horizontal square wave grating, 0.1 cycle/degree) at 1.07 reversals per second (rps) for Argus II subjects and 3.37 rps for controls. Argus II patients had both eyes patched, viewing the pattern solely through their implant. Controls viewed the pattern monocularly, either with their best-corrected vision or with simulated visual reduction (field restriction, added blur or reduced display contrast). RESULTS: VEPs recorded in Argus II patients displayed a similar shape to normal VEPs when controls viewed the pattern without simulated visual reduction. In sighted controls, adding blur significantly delayed the P100 peak time by 8.7 ms, 95% CI (0.9, 16.6). Reducing stimulus contrast to 32% and 6% of full display contrast significantly decreased P100 amplitude to 55% (37%, 82%) and 20% (13%, 31%), respectively. Restriction on the field of view had no impact on either the amplitude or the peak latency of P100. CONCLUSION: The early visual cortex in retinal prosthesis users remains responsive to retinal input, showing a similar response profile to that of sighted controls. Pattern-reversal VEP offers valuable insights for objectively evaluating artificial vision therapy systems (AVTSs) when selecting, fitting and training implant users, but the uncertainties in the exact timing and location of electrode stimulation must be considered when interpreting the results.

Surgical techniques for optimal lens management of posterior segment metallic intraocular foreign body removal: a case series.

PURPOSE: We describe three different approaches for lens management in cases of metallic IOFBs involving the posterior segment. METHODS: All consecutive posterior segment metallic IOFB cases from 2012 to 2023 at a single institution were included in this retrospective case series. Surgical outcomes and surgical videos are presented. RESULTS: A total of 25 metallic IOFB cases were included. In 9 cases, there was no significant lens involvement, therefore not requiring lens extraction at the time of IOFB removal. In 8 cases with traumatic cataract, lens extraction sparing the anterior lens capsule was performed with IOFB removal. In 8 cases, both lens extraction and lens capsule removal were required at the time of IOFB removal. CONCLUSION: We demonstrate our algorithm to capsular management in patients who present with IOFB with good visual outcomes in follow-up.

Visual outcomes of the surgical rehabilitative process following open globe injury repair.

Background: The path of rehabilitation of an eye after open globe injury (OGI) may require multiple additional secondary surgeries after the initial repair. Although much has been studied regarding the outcomes of secondary surgeries after open globe repair, it can be challenging to understand the possible implications of the surgical rehabilitative process. This retrospective study considers the benefits of the required additional secondary surgeries for a consecutive series of OGI patients. Methods: OGI patients who had at least one additional surgery after the initial open globe repair (OGR) were studied retrospectively. Additional inclusion criteria included: follow up of at least 12 months since the initial injury and at least 3 months since their most recent surgery, and no additional planned interventions. Preoperative visual acuity was compared to final visual acuity. Additionally, the odds of achieving ambulatory vision (≥20/800) and reading vision (≥20/40) were calculated after each indicated consecutive surgery. Results: A cohort of 74 eyes from 73 patients met our inclusion criteria. These patients underwent a mean of two additional surgeries. The mean logMAR VA improved from 2.3 (HM) at presentation to 1.4 (20/150), or a 9-line Snellen equivalent improvement. Upon reaching their final visit status, 50% of patients had achieved ambulatory vision and 30% of patients had achieved reading vision. The odds of achieving ambulatory vision after completion of all the rehabilitative surgical process compared to the vision prior to the secondary rehabilitative surgery were higher (OR: 19.1, 95% CI: 7.9 - 30.4, p = 0.0008) as were the odds of achieving reading vision (OR: 4.6, 95% CI: 0.2 - 9.0, p = 0.04). With subsequent second, third, and fourth additional surgeries, the odds of achieving either ambulatory or reading vision at the final visit compared to their preoperative visual acuities were not significant (p > 0.05) but the visual acuity continued to trend toward visual improvement. Conclusion: Approximately 50% of individuals who required additional surgery at UMN achieved ambulatory vision and 30% achieved reading vision. The odds of visual improvement through the surgical rehabilitative process were very high, with the greatest gains generally achieved after the first surgery.

The Logistical Backbone of Photoreceptor Cell Function: Complementary Mechanisms of Dietary Vitamin A Receptors and Rhodopsin Transporters.

In this review, we outline our current understanding of the mechanisms involved in the absorption, storage, and transport of dietary vitamin A to the eye, and the trafficking of rhodopsin protein to the photoreceptor outer segments, which encompasses the logistical backbone required for photoreceptor cell function. Two key mechanisms of this process are emphasized in this manuscript: ocular and systemic vitamin A membrane transporters, and rhodopsin transporters. Understanding the complementary mechanisms responsible for the generation and proper transport of the retinylidene protein to the photoreceptor outer segment will eventually shed light on the importance of genes encoded by these proteins, and their relationship on normal visual function and in the pathophysiology of retinal degenerative diseases.

QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration.

DNA methylation provides a crucial epigenetic mark linking genetic variations to environmental influence. We have analyzed array-based DNA methylation profiles of 160 human retinas with co-measured RNA-seq and >8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 methylation quantitative trait loci and 12,505 expression quantitative trait loci) and 13,747 DNA methylation loci affecting gene expression, with over one-third specific to the retina. Methylation and expression quantitative trait loci show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism. Summary data-based Mendelian randomization and colocalization analyses identify 87 target genes where methylation and gene-expression changes likely mediate the genotype effect on age-related macular degeneration. Integrated pathway analysis reveals epigenetic regulation of immune response and metabolism including the glutathione pathway and glycolysis. Our study thus defines key roles of genetic variations driving methylation changes, prioritizes epigenetic control of gene expression, and suggests frameworks for regulation of macular degeneration pathology by genotype-environment interaction in retina.

The Clinical Findings, Pathogenic Variants, and Gene Therapy Qualifications Found in a Leber Congenital Amaurosis Phenotypic Spectrum Patient Cohort.

This retrospective study examines the clinical characteristics and underlying genetic variants that exist in a Leber congenital amaurosis (LCA) patient cohort evaluated at the inherited retinal disease (IRD) clinic at the University of Minnesota (UMN)/M Health System. Our LCA cohort consisted of 33 non-syndromic patients and one patient with Joubert syndrome. We report their relevant history, clinical findings, and genetic testing results. We monitored disease presentation utilizing ocular coherence tomography (OCT) and fundus autofluorescence (FAF). Electroretinogram testing (ERG) was performed in patients when clinically indicated. Next-generation sequencing (NGS) and genetic counseling was offered to all evaluated patients. Advanced photoreceptor loss was noted in 85.7% of the subjects. All patients who underwent FAF had findings of either a ring of macular hypo/hyper AF or peripheral hypo-AF. All patients had abnormal ERG findings. A diagnostic genetic test result was identified in 74.2% of the patients via NGS single-gene testing or panel testing. Two patients in our cohort qualified for Luxturna® and both received treatment at the time of this study. These data will help IRD specialists to understand the genetic variants and clinical presentations that characterize our patient population in the Midwest region of the United States.