HANDHELD SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IMAGING THROUGH THE UNDILATED PUPIL IN INFANTS BORN PRETERM OR WITH HYPOXIC INJURY OR HYDROCEPHALUS.

PURPOSE: The authors investigated feasibility of undilated handheld spectral domain optical coherence tomography (SDOCT) retinal imaging in preterm infants and children with neurologic abnormalities. METHODS: Under an institutional review board-approved protocol, the authors attempted handheld SDOCT imaging of the retina, choroid, and optic nerve in infants and young children without pupil dilation. Scans were analyzed for quality and successful capture of foveal, optic nerve, and retinal structural parameters and abnormalities. RESULTS: The authors obtained images through an undilated pupil of 11 infants/children over 28 eye imaging sessions, 27 at the bedside without sedation, and one under anesthesia. Infants had retinopathy of prematurity (n = 8), hypoxic ischemic encephalopathy (n = 2), or obstructive hydrocephalus (n = 1 child). Pupil sizes ranged from 1.0 mm to 3.5 mm. The authors captured fovea and optic nerve scans in 25/28 eye imaging sessions, with scans of adequate quality to discern prespecified foveal and optic nerve morphology, and of the 25 sessions, the choroidal-scleral junction was visible in all but 6 sessions. CONCLUSION: Undilated, handheld SDOCT imaging is a potential alternative method to evaluate the retina and optic nerve in patients with relative contraindication to pharmacological pupil dilation. This approach will enable the study of the eye-brain connection and ocular manifestations of neurologic diseases.

Systemic and ocular outcomes in patients with young-onset type 2 diabetes.

PURPOSE: To analyze the systemic and ocular outcomes in patients with young-onset type 2 diabetes (YO-DM2) based on grade of presenting diabetic retinopathy (DR). METHODS: Retrospective cohort study analysis of empaneled patients with type 2 diabetes <40 years old with retinopathy screening within the Los Angeles Department of Health Services between 01/01/2017-07/01/2021 were included. Patients were stratified based on presenting severity of DR determined on fundus photographs or clinical examination. Patient's systemic co-morbidities and ocular outcomes were then compared across each group. Procedural (e.g. intravitreal injections) and surgical interventions (e.g. pars plana vitrectomy) were documented as performed by the treating physician. RESULTS: 2795 patients were screened from 12,456 patients diagnosed with diabetes younger than age 40 (22.4 %). Of these, 1496 patients were diagnosed with type 2 DM. 1084 (72.4 %) of patients presented without DR, 307 (20.5 %) presented with non-proliferative diabetic retinopathy (NPDR), and 105 (7.0 %) of patients presented with proliferative diabetic retinopathy (PDR). Increasing presenting diabetic retinopathy severity was associated with longer duration of diabetes, greater systemic comorbidities (e.g. diabetic foot disease, neuropathy, chronic kidney or end stage renal disease), worse baseline and final visual acuity, and required more procedural and surgical interventions. CONCLUSIONS: Worse presenting DR severity in patients young-onset type 2 diabetes was associated with greater comorbid systemic and ocular disease with worse visual acuity outcomes. <1 % of patients without diabetic retinopathy or with mild NPDR were likely to progress to PDR. Diabetic kidney disease was an independent risk factor for developing neovascular glaucoma and retinal detachments. Prompt evaluation and intervention in patients with YO-DM2 may help reduce the associated systemic and ocular morbidity.

Evaluation of 3D tablet-based stereoacuity test ASTEROID in children with normal and abnormal visual acuity.

PURPOSE: To assess the utility of 3D, tablet-based, glasses-free Accurate STEReotest (ASTEROID) in children compared with the Titmus test. METHODS: Children aged 5-13 years were enrolled in a single-center, nonrandomized, observational comparison study and analyzed by age (5-7 vs 8-13 years) and visual acuity (20/25 or better in both eyes vs abnormal). Each participant underwent both the ASTEROID and Titmus stereoacuity tests. Stereoacuity was defined as fine (≤60 arcsec), moderate (61-200 arcsec), coarse (201-1199 arcsec), or very coarse to nil (≥1200 arcsec). Agreement between the tests was assessed using a weighted kappa (κ) statistic based on all four categories. RESULTS: A total of 112 children were included: 28 aged 5-7 with normal visual acuity, 30 aged 5-7 with abnormal visual acuity, 34 aged 8-13 with normal visual acuity, and 20 aged 8-13 with abnormal visual acuity. Mean ASTEROID score was 688 ± 533 arcsec (range, 13-1200 arcsec). Agreement between ASTEROID and Titmus test scores for participants overall was moderate (κ = 0.52). By subgroup, agreement was fair for children 5-7 with abnormal visual acuity (κ = 0.31), moderate for children 5-7 with normal visual acuity (κ = 0.47) and children 8-13 with normal visual acuity (κ = 0.42), and substantial for children 8-13 with abnormal visual acuity (κ = 0.76). Where ASTEROID and Titmus score group varied, ASTEROID score was poorer in 94% (47/50) of cases. CONCLUSIONS: ASTEROID is a digital, tablet-based test that evaluates global stereopsis, does not require glasses, and provides a continuum of scores. Among children, ASTEROID has good agreement with the Titmus test; however, it may be more sensitive at detecting stereovision deficits. Further study is necessary to determine which test is more accurate.

Fungal Infection After Descemet Membrane Endothelial Keratoplasty: Incidence and Outcomes.

PURPOSE: The aim of the study was to describe the incidence, presentation, management, and outcomes of fungal infection after Descemet membrane endothelial keratoplasty (DMEK). METHODS: Retrospective case series of culture-proven fungal infections after DMEK reported in the literature, directly by surgeons, and to the Eye Bank Association of America from January 1, 2011, to December 31, 2020. RESULTS: The domestic incidence of fungal infections, fungal keratitis, and fungal endophthalmitis after DMEK from 2011 to 2020 was 3.5, 1.3, and 2.2 per 10,000 cases, respectively, with no significant increasing trend. Thirty-four cases were identified, 14 (41.2%) published and 20 (58.8%) unpublished. Donor tissue fungal cultures were performed in 20 of the 34 (58.8%) cases and were positive in 19 of the 20 (95.0%), all but one Candida species. Recipient fungal cultures were performed in 29 of the 34 (85.3%) cases and were positive in 26 of the 29 (89.7%), all but one Candida species. Infection presented a mean of 33 ± 38 days (median 23, range 2-200, outlier 949) after transplantation: 25 (73.5%) with endophthalmitis and 9 (26.5%) with keratitis. Topical, intrastromal, intracameral, intravitreal, or systemic antifungal therapy was used in all 27 eyes with treatment data. Surgical intervention (DMEK explantation or partial removal, repeat endothelial keratoplasty, penetrating keratoplasty, and/or pars plana vitrectomy) was required in 21 of the 27 (77.8%) eyes. The corrected distance visual acuity at the last follow-up was ≥20/40 in 13 of the 27 (48.1%) eyes and counting fingers or worse in 6 of the 27 (22.2%) eyes. CONCLUSIONS: Fungal infection is a rare but serious complication of DMEK that results in counting fingers or worse corrected distance visual acuity in nearly a quarter of eyes.

Antibiotics prior to embryo transfer in ART.

BACKGROUND: Embryo transfer (ET) involves the placement of one or more embryos into the uterine cavity, usually by passing a catheter through the cervical os. ET is the final step in an assisted reproductive technology (ART) cycle, where a woman has undergone controlled ovarian stimulation, egg retrieval and in vitro fertilisation of her eggs. Despite the transfer of high quality embryos, many ETs do not result in a pregnancy. There are many factors which may affect the success of ET, including the presence of upper genital tract microbial colonisation. The administration of antibiotics prior to ET has been suggested as an intervention to reduce levels of microbial colonisation and hence improve pregnancy rates. OBJECTIVES: To evaluate the effectiveness and safety of antibiotic administration prior to ET during ART cycles. SEARCH METHODS: We searched the Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library, MEDLINE, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Ovid MEDLINE® Daily and Ovid MEDLINE® (from inception to February 2011), Ovid EMBASE (January 2010 to February 2011), Ovid PsycINFO, CINAHL, LILACS, trial registers for ongoing and registered trials, citation indexes, ClinicalStudyResults, PubMed, OpenSIGLE database and for for herbal and complimentary therapy protocols and reviews. SELECTION CRITERIA: Only randomised controlled trials were included. DATA COLLECTION AND ANALYSIS: The titles and abstracts of articles identified by the search were screened by one review author for eligibility. Two review authors then independently examined the full text articles for suitability for inclusion in the review. Data were extracted independently by two review authors. MAIN RESULTS: We identified four potential studies, of which three were excluded.The included trial reported clinical pregnancy rates but not live births. There was no evidence of a difference in clinical pregnancy rate between those receiving an amoxycillin and clavulanic acid antibiotic combination (64/178: 36%) and those not (61/172: 35.5%) (OR1.02, 95% CI 0.66 to 1.58). Genital tract colonisation was significantly reduced in women receiving this antibiotic regimen (OR 0.59, 95% CI 0.37 to 0.95). AUTHORS' CONCLUSIONS: This review suggests that the administration of amoxycillin and clavulanic acid prior to embryo transfer reduced upper genital tract microbial contamination but did not alter clinical pregnancy rates. The effect of this intervention on live birth is unknown. There are no data from randomised controlled trials to support or refute other antibiotic regimens in this setting.Future research is warranted to assess the efficacy of alternative antibiotic regimens. Researchers should assess live birth as the primary outcome and address quantitative microbial colonization as a secondary outcome.

Eyelid nystagmus in a child with cardiofaciocutaneous syndrome associated with BRAF mutation.

Eyelid nystagmus, thought to reflect midbrain or hindbrain disease, is a rare condition that typically occurs in association with neurologic and neuroophthalmic abnormalities. Cardiofaciocutaneous (CFC) syndrome associated with B-raf protooncogene serine/threonine kinase (BRAF) mutation is a complex syndrome that is associated with neurologic and neuroophthalmologic abnormalities. We report the case of a 4-year-old girl with CFC syndrome with global developmental delay who was referred for evaluation of alternating exotropia, right-sided dissociated vertical deviation, bilateral upgaze nystagmus, and bilateral eyelid fluttering. Neurological work-up revealed bilateral frontocentral sharp waves without seizure activity on electroencephalogram and mild left-sided cerebral volume loss on magnetic resonance imaging. To our knowledge, this is the first reported case of eyelid nystagmus in CFC syndrome. Eyelid nystagmus warrants neurological evaluation, because it is commonly associated with significant neurological abnormalities.

Isolation, Culture, and Genetic Engineering of Mammalian Primary Pigment Epithelial Cells for Non-Viral Gene Therapy.

Age-related macular degeneration (AMD) is the most frequent cause of blindness in patients >60 years, affecting ~30 million people worldwide. AMD is a multifactorial disease influenced by environmental and genetic factors, which lead to functional impairment of the retina due to retinal pigment epithelial (RPE) cell degeneration followed by photoreceptor degradation. An ideal treatment would include the transplantation of healthy RPE cells secreting neuroprotective factors to prevent RPE cell death and photoreceptor degeneration. Due to the functional and genetic similarities and the possibility of a less invasive biopsy, the transplantation of iris pigment epithelial (IPE) cells was proposed as a substitute for the degenerated RPE. Secretion of neuroprotective factors by a low number of subretinally-transplanted cells can be achieved by Sleeping Beauty (SB100X) transposon-mediated transfection with genes coding for the pigment epithelium-derived factor (PEDF) and/or the granulocyte macrophage-colony stimulating factor (GM-CSF). We established the isolation, culture, and SB100X-mediated transfection of RPE and IPE cells from various species including rodents, pigs, and cattle. Globes are explanted and the cornea and lens are removed to access the iris and the retina. Using a custom-made spatula, IPE cells are removed from the isolated iris. To harvest RPE cells, a trypsin incubation may be required, depending on the species. Then, using RPE-customized spatula, cells are suspended in medium. After seeding, cells are monitored twice per week and, after reaching confluence, transfected by electroporation. Gene integration, expression, protein secretion, and function were confirmed by qPCR, WB, ELISA, immunofluorescence, and functional assays. Depending on the species, 30,000-5 million (RPE) and 10,000-1.5 million (IPE) cells can be isolated per eye. Genetically modified cells show significant PEDF/GM-CSF overexpression with the capacity to reduce oxidative stress and offers a flexible system for ex vivo analyses and in vivo studies transferable to humans to develop ocular gene therapy approaches.

Regression of Cystoid Macular Edema Three Weeks After Laser for Retinopathy of Prematurity.

Cystoid macular edema (CME) has been reported in the neonatal period associated with preterm birth; however, its pathogenesis remains unclear and is likely multifactorial. The authors report the case of a preterm infant imaged using optical coherence tomography (OCT), which revealed severe CME that regressed after laser treatment. Because laser for retinopathy of prematurity aims to reduce vascular endothelial growth factor (VEGF) levels, this case considers the possibility of VEGF-mediated CME pathogenesis. Further, the authors provide additional evidence of the value of OCT for noninvasive visualization of the preterm retina; the modality provides an effective way to evaluate and monitor progression of CME. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:472-475.].

Morphological characteristics of early- versus late-onset macular edema in preterm infants.

Macular images of infants with early-onset edema (occurring at or before 33 weeks' postmenstrual age [PMA]) and infants with late-onset edema (at or after 36 weeks' PMA) were compared. At first appearance, early-onset edema has a more severe morphology, with foveal bulging and elongated cystoid spaces than late-onset edema, which presents as small cystoid spaces outside the foveal center. Morphological variations may be an indicator of the underlying cause of edema in preterm infants. The presence of mostly parafoveal small cystoid spaces in the late-onset edema group may be suggestive of an association with neurological injury.