Autosomal-dominant macular dystrophy linked to a chromosome 17 tandem duplication.

Hereditary macular dystrophies (HMDs) are a genetically diverse group of disorders that cause central vision loss due to photoreceptor and retinal pigment epithelium (RPE) damage. We investigated a family with a presumed novel autosomal-dominant HMD characterized by faint, hypopigmented RPE changes involving the central retina. Genome and RNA sequencing identified the disease-causing variant to be a 560 kb tandem duplication on chromosome 17 [NC_000017.

Acyl-CoA synthetase 6 controls rod photoreceptor function and survival by shaping the phospholipid composition of retinal membranes.

The retina is light-sensitive neuronal tissue in the back of the eye. The phospholipid composition of the retina is unique and highly enriched in polyunsaturated fatty acids, including docosahexaenoic fatty acid (DHA). While it is generally accepted that a high DHA content is important for vision, surprisingly little is known about the mechanisms of DHA enrichment in the retina.

Validation and Feasibility of the Postnatal Growth and Retinopathy of Prematurity Retinal Screening Criteria at a Level IV Tertiary Care Neonatal Intensive Care Unit.

Objective: Retinopathy of prematurity (ROP) is detected in preterm infants by standardized screening programs, but in general, they have poor sensitivity. The Postnatal Growth and Retinopathy of Prematurity (G-ROP) algorithm uses weight gain to predict ROP superior reported sensitivity. Our objectives are to (1) independently validate the sensitivity of G-ROP criteria for the detection of ROP in infants born at >28 weeks' gestation in a tertiary care unit in the United States and (2) to calculate the cost savings associated with a potential reduction in examinations.

A Bietti Crystalline Dystrophy Mouse Model Shows Increased Sensitivity to Light-Induced Injury.

Bietti crystalline corneo-retinal dystrophy (BCD) is an autosomal recessive inherited retinal dystrophy characterized by multiple shimmering yellow-white deposits in the posterior pole of the retina in association with atrophy of the retinal pigment epithelium (RPE), pigment clumps, and choroidal atrophy and sclerosis. Blindness and severe visual damage are common in late-stage BCD patients. We generated a knockout mouse model to investigate the pathogenesis of BCD.

Pharmacokinetics and metabolism in mouse retina of bis-allylic deuterated docosahexaenoic acid (D-DHA), a new dry AMD drug candidate.

Docosahexaenoic acid (DHA; 22:6n-3) rich photoreceptors function in a highly oxidizing microenvironment. Lipid peroxidation and inflammation contribute to initiation and progression of eye diseases including age-related macular degeneration (AMD). Deuteration of DHA at the bis-allylic positions (D-DHA) increases its resilience to oxidative damage in vitro.

Ocular malignancies treated with iodine-125 low dose rate (LDR) brachytherapy at a single high-volume institution: A retrospective review.

The aim of our study is to document our cases of choroidal melanoma treated with low dose rate (LDR) brachytherapy and to correlate the dosimetry and radiobiology with clinical effects and oncologic outcomes. Data from 157 patients treated from 2014 to 2018 with LDR brachytherapy were used for this investigation. Treatments used a collaborative ocular melanoma study eye plaque and Iodine-125 radioactive seeds.

Association of Cardiovascular Disease with Retinopathy of Prematurity.

Purpose: To determine the associations of presence and types of cardiovascular diseases (CVDs) with development of retinopathy of prematurity (ROP) in premature infants undergoing ROP examinations.

Study Design: We performed secondary analyses of data from the multi-center Postnatal Growth and ROP Validation Study (GROP-2). CVD was categorized based on pulmonary blood flow (PBF), systemic blood flow (SBF), pulmonary hypertension (PPHN), or dysrhythmia.

Fill levels, cost comparisons, and expulsion force requirements of commonly used topical ophthalmic steroids.

Purpose: To determine volume fill levels, estimated costs, and force expulsion requirements per bottle of topical ophthalmic steroids commonly used in the United States.

Setting: Tertiary care academic referral center.

Design: Prospective laboratory investigation.

Signaling roles of phosphoinositides in the retina.

The field of phosphoinositide signaling has expanded significantly in recent years. Phosphoinositides (also known as phosphatidylinositol phosphates or PIPs) are universal signaling molecules that directly interact with membrane proteins or with cytosolic proteins containing domains that directly bind phosphoinositides and are recruited to cell membranes. Through the activities of phosphoinositide kinases and phosphoinositide phosphatases, seven distinct phosphoinositide lipid molecules are formed from the parent molecule, phosphatidylinositol.

Medical management and visual rehabilitation of limbal niche dysfunction.

Limbal niche dysfunction (LND) has been described as a medically reversible form of limbal stem cell deficiency. The current literature is sparse regarding therapeutic options to improve visual function after stabilization of the disease. A 61-year-old monocular woman with an extensive medical and ocular history presented with long-standing recalcitrant epitheliopathy in both eyes.

Temporal Distribution Patterns of Alexa Fluor 647-Conjugated CeNPs in the Mouse Retina After a Single Intravitreal Injection.

Intravitreal (IVT) injection of ophthalmic therapeutics is the most widely used drug delivery route to the posterior segment of the eye. We employed this method to deliver our inorganic, catalytic antioxidant, cerium oxide nanoparticles (CeNPs), to rodent models of retinal degeneration. A single IVT of CeNPs delays disease progression.

Reproducibility of Ocular Surface Staining in the Assessment of Sjögren Syndrome-Related Keratoconjunctivitis Sicca: Implications on Disease Classification.

Objective: The objective of this study was to assess the performance and reproducibility of the two currently used ocular surface staining scores in the assessment of keratoconjunctivitis sicca in Sjögren syndrome (SS) research classification.

Methods: In a multidisciplinary clinic for the evaluation of sicca, we performed all tests for the American European Consensus Group (AECG) and the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria, including the van Bijsterveld score (vBS) and the Ocular Staining Score (OSS), in 994 participants with SS or with non-SS sicca. We analyzed the concordance between the scores, the diagnostic accuracy and correlation with clinical variables, and interrater and intrasubject reproducibility.

Radiation treatment to a postresection primary mucoepidermoid carcinoma (MEC) of the conjunctiva with positive margins at the Tenon's fascia-A case study.

The primary occurrence of mucoepidermoid carcinoma (MEC) of the conjunctiva is extremely rare, aggressive, and easily mistaken for squamous cell carcinoma. With fewer than 50 cases reported in the literature, there is no consensus on the most effective treatment. Radiation is an alternative to enucleation or orbital exenteration with the potential of eye preservation.

Retinal degeneration mutation in Sftpa1tm1Kor/J and Sftpd -/- targeted mice.

Surfactant proteins are important collectin immune molecules with a wide distribution throughout the body, including the ocular system. Mice with gene deletions for the surfactant protein genes Sftpa1 and Sftpd were observed to have visual impairment and thinning of the outer nuclear layers of the retina. We hypothesized that gene deletion of Sftpa1 and Sftpd (Sftpa1tm1Kor/J and Sftpd-/-) results in early retinal degeneration in these mice.

Elovl4 5-bp deletion does not accelerate cone photoreceptor degeneration in an all-cone mouse.

Mutations in the elongation of very long chain fatty acid 4 (ELOVL4) gene cause Stargardt macular dystrophy 3 (STGD3), a rare, juvenile-onset, autosomal dominant form of macular degeneration. Although several mouse models have already been generated to investigate the link between the three identified disease-causing mutations in the ELOVL4 gene, none of these models recapitulates the early-onset cone photoreceptor cell death observed in the macula of STGD3 patients. To address this specifically, we investigated the effect of mutant ELOVL4 in a mouse model with an all-cone retina.

The B3 Subunit of the Cone Cyclic Nucleotide-gated Channel Regulates the Light Responses of Cones and Contributes to the Channel Structural Flexibility.

Cone photoreceptor cyclic nucleotide-gated (CNG) channels play a pivotal role in cone phototransduction, which is a process essential for daylight vision, color vision, and visual acuity. Mutations in the cone channel subunits CNGA3 and CNGB3 are associated with human cone diseases, including achromatopsia, cone dystrophies, and early onset macular degeneration. Mutations in CNGB3 alone account for 50% of reported cases of achromatopsia.

Defining the catalytic activity of nanoceria in the P23H-1 rat, a photoreceptor degeneration model.

Purpose: Inorganic catalytic nanoceria or cerium oxide nanoparticles (CeNPs) are bona fide antioxidants that possess regenerative radical scavenging activities in vitro. Previously, we demonstrated that CeNPs had neuroprotective and anti-angiogenic properties in rodent retinal degeneration and neovascularization models. However, the cellular mechanisms and duration of the catalytic activity of CeNPs in preventing photoreceptor cell loss are still unknown.

Pulmonary surfactant protein a is expressed in mouse retina by Müller cells and impacts neovascularization in oxygen-induced retinopathy.

Purpose: Surfactant protein A (SP-A) up-regulates cytokine expression in lung disease of prematurity. Here we present data that for the first time characterizes SP-A expression and localization in the mouse retina and its impact on neovascularization (NV) in the mouse.

Methods: Retinal SP-A was localized in wild-type (WT) mice with the cell markers glutamine synthetase (Müller cells), neurofilament-M (ganglion cells), glial acid fibrillary acid protein (astrocytes), and cluster of differentiation 31 (endothelial cells).

Boston keratoprosthesis type 1 for herpes simplex and herpes zoster keratopathy.

Purpose: The aim of this study was to evaluate and compare the outcomes of Boston keratoprosthesis type 1 (Kpro-1) in eyes with herpes simplex virus (HSV) and herpes zoster virus (HZV) keratopathy.

Methods: A retrospective review was performed of the medical records of every patient treated with a Boston Kpro-1 at the University of Iowa Hospitals and Clinics between January 1, 2008 and July 1, 2012. Eyes with visual loss due to HSV or HZV keratopathy were included in the statistical analysis.

Nanoceria as bona fide catalytic antioxidants in medicine: what we know and what we want to know….

Cerium oxide (CeO2) nanoparticles, CeNPs or nanoceria are inorganic and possess catalytic antioxidant activity. They scavenge reactive oxygen species and act as an oxygen buffer. Their application in industry is well-established.

Catalytic nanoceria are preferentially retained in the rat retina and are not cytotoxic after intravitreal injection.

Cerium oxide nanoparticles (nanoceria) possess catalytic and regenerative radical scavenging activities. The ability of nanoceria to maintain cellular redox balance makes them ideal candidates for treatment of retinal diseases whose development is tightly associated with oxidative damage. We have demonstrated that our stable water-dispersed nanoceria delay photoreceptor cell degeneration in rodent models and prevent pathological retinal neovascularization in vldlr mutant mice.

Loss of caveolin-1 impairs retinal function due to disturbance of subretinal microenvironment.

Caveolin-1 (Cav-1), an integral component of caveolar membrane domains, is expressed in several retinal cell types, including photoreceptors, retinal vascular endothelial cells, Müller glia, and retinal pigment epithelium (RPE) cells. Recent evidence links Cav-1 to ocular diseases, including autoimmune uveitis, diabetic retinopathy, and primary open angle glaucoma, but its role in normal vision is largely undetermined. In this report, we show that ablation of Cav-1 results in reduced inner and outer retinal function as measured, in vivo, by electroretinography and manganese-enhanced MRI.