PURPOSE: Evaluate the differences between clinical visual acuity (VA) as recorded in medical records and electronic ETDRS (eETDRS) protocol VA measurements and factors affecting the size of the differences. DESIGN: Retrospective chart review. PARTICIPANTS: Study and fellow eyes of participants enrolled in DRCR Retina Network Protocols AC and AE (diabetic macular edema), and W (non-proliferative diabetic retinopathy) with clinical VA recorded within 3 months before the protocol visit. METHODS: Linear mixed models evaluated the differences and their association with patient and ocular factors in univariable and multivariable models, with random effects for correlations within sites and participants. MAIN OUTCOME MEASURE: Difference between VA letter scores measured by eETDRS during a study protocol visit versus measured by Snellen during a regular clinical visit (Snellen fraction converted to eETDRS). RESULTS: Data from 1016 eyes (511 participants) across 74 sites were analyzed. The mean VA measurements were 68.6 letters (Snellen equivalent 20/50) at the clinical visit and 76.3 letters (Snellen equivalent 20/32) at the protocol visit, with a mean (standard deviation, SD) of 26 (21) days between visits. Mean (SD) protocol VA was better than clinical VA by 7.6 (9.6) letters overall, 10.7 (12.6) letters in eyes with clinical VA ≤20/50 (n = 376) and 5.8 (6.6) letters in eyes with clinical VA ≥20/40 (n = 640). On average, the difference between clinical and protocol VA was 1.3 letters smaller for every 1-line (5 letters) increase in clinical VA (p < 0.001). Mean (SD) differences by clinical correction of refractive error were 3.9 (9.0) letters with refraction, 6.9 (9.2) letters with glasses/contact lenses, 7.9 (11.5) letters with pinhole and 9.8 (9.3) letters without correction (p=0.06). CONCLUSION: On average, clinical Snellen VA is likely to be 1-2 lines worse than eETDRS protocol refraction and VA testing, which may partly explain why clinical practice does not always replicate clinical trial results. Eyes with lower clinical measurements and eyes tested without clinical refraction tended to have larger differences. Considering the potential discrepancies between clinical and protocol VA measurements, refracting eyes in the clinic may benefit patients when determining treatment plans and study referrals based on vision.

Despite rigorous investigations, the hydrogels currently available to replace damaged tissues, such as the cornea, cannot fulfill mechanical and structural requirements and, more importantly, cannot be sutured into host tissues due to the lack of hierarchical structures to dissipate exerted stress. In this report, solution electrospinning of polycaprolactone (PCL), protein-based hydrogel perfusion, and layer-by-layer stacking are used to generate a hydrogel-microfiber composite with varying PCL fiber diameters and hydrogel concentrations. Integrating PCL microfibers into the hydrogel synergistically improves the mechanical properties and suturability of the construct up to 10-fold and 50-fold, respectively, compared to the hydrogel and microfiber scaffolds alone, approaching those of the corneal tissue. Human corneal cells cultured on composites are viable and can spread, proliferate, and retain phenotypic characteristics. Moreover, corneal stromal cells migrate into the scaffold, degrade it, and regenerate the extracellular matrix. The current hydrogel reinforcing system paves the way for producing suturable and, therefore, transplantable tissue constructs with desired mechanical properties.

PURPOSE: To compare the types and dosages of anti-VEGFs to ascertain whether specific dosages or types of injection were associated with retreatment in clinical practice in the US. DESIGN: Multicenter, retrospective, consecutive series. SUBJECTS: Patients with ROP treated with anti-VEGF injections from 2007 to 2021. METHODS: Sixteen sites from the US participated. Data collected included demographics, birth characteristics, examination findings, type and dose of anti-VEGF treatment, retreatment rates, and time to retreatment. Comparisons of retreatment rates between bevacizumab and ranibizumab intravitreal injections were made. MAIN OUTCOME MEASURES: Relative rate of retreatment between varying types of anti-VEGF therapy, including bevacizumab and ranibizumab, and the various dosages used for each. RESULTS: Data from 873 eyes of 661 patients (61% males and 39% females) were collected. After exclusion of 40 eyes treated with laser prior to anti-VEGF injection and 266 eyes retreated with laser at or beyond 8 weeks after the initial anti-VEGF treatment, 567 eyes of 307 patients (63% males and 37% females) remained and were included in the primary analysis. There was no difference between the no-retreatment and retreatment groups in terms of birthweight, gestational age, age at first injection, ROP stages, or number of involved clock hours. The retreatment group had a larger percentage of A-ROP (34 vs 18%, P < .001), and greater percentage of Zone 1 ROP (49 vs 34%, P = .001) than the no retreatment group. Ranibizumab use was associated with a higher rate of retreatment than bevacizumab use (58% vs 37%, P < .001), while the rate of retreatment was not associated with a specific dose of ranibizumab (R2 = .67, P = .32). Meanwhile, lower doses of bevacizumab were associated with higher rates of retreatment compared to the higher doses (R2 = .84, P = .01). There was a dose specific trend with higher doses trending towards lower retreatments for bevacizumab. CONCLUSIONS: In a multicenter study of ROP patients initially treated with anti-VEGF therapy, ranibizumab and lower dose bevacizumab use were associated with an increased rate of retreatment when compared to higher dose bevacizumab.

Over the past decades, substantial advances in neonatal medical care have increased the survival of extremely premature infants. However, there continues to be significant morbidity associated with preterm birth with common complications including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), neuronal injury such as intraventricular hemorrhage (IVH) or hypoxic ischemic encephalopathy (HIE), as well as retinopathy of prematurity (ROP). Common developmental immune and inflammatory pathways underlie the pathophysiology of such complications providing the opportunity for multisystem therapeutic approaches. To date, no single therapy has proven to be effective enough to prevent or treat the sequelae of prematurity. In the past decade mesenchymal stem/stromal cell (MSC)-based therapeutic approaches have shown promising results in numerous experimental models of neonatal diseases. It is now accepted that the therapeutic potential of MSCs is comprised of their secretome, and several studies have recognized the small extracellular vesicles (sEVs) as the paracrine vector. Herein, we review the current literature on the MSC-EVs as potential therapeutic agents in neonatal diseases and comment on the progress and challenges of their translation to the clinical setting.

PURPOSE OF REVIEW: This review paper aims at discussing pathogenesis, etiology, clinical features, management, and prognosis of OPN. RECENT FINDINGS: Optic perineuritis (OPN) is an inflammatory process primarily involving the optic nerve sheath. Clinically, OPN usually presents with unilateral, gradual decline of visual function, eye pain, and/or pain on eye movements, disc edema and various features of optic nerve dysfunction, including visual field defects. It can mimic typical optic neuritis. In most cases of OPN, the disease is isolated with no specific etiology being identified, however, it can also occur secondary to a wide range of underlying systemic diseases. OPN is clinically diagnosed and radiologically confirmed based on the finding of circumferential perineural enhancement of the optic nerve sheath on magnetic resonance imaging (MRI). SUMMARY: Unlike optic nerve, OPN is not typically self-limited without treatment. High-dose oral corticosteroids are the mainstay of treatment in OPN. The initiation of therapy usually causes rapid and dramatic improvement in signs and symptoms. In general, OPN usually has a relatively good visual prognosis, which is influenced by delays between the onset of visual loss and the initiation of steroid therapy as well as the presence of underlying systemic diseases.

Inherited retinal diseases (IRDs) are a genetically and phenotypically heterogeneous group of genetic eye disorders. There are more than 300 disease entities, and together this group of disorders affects millions of people globally and is a frequent cause of blindness or low-vision certification. However, each type is rare or ultra-rare. Characteristically, the impaired vision in IRDs is due to retinal photoreceptor dysfunction and loss resulting from mutation in a gene that codes for a retinal protein. Historically, IRDs have been considered incurable and individuals living with these blinding conditions could be offered only supportive care. However, the treatment landscape for IRDs is beginning to evolve. Progress is being made, driven by improvements in understanding of genotype-phenotype relationships, through advances in molecular genetic testing and retinal imaging. Alongside this expanding knowledge of IRDs, the current era of precision medicine is fueling a growth in targeted therapies. This has resulted in the first treatment for an IRD being approved. Several other therapies are currently in development in the IRD space, including RNA-based therapies, gene-based therapies (such as augmentation therapy and gene editing), cell therapy, visual prosthetics, and optogenetics. RNA-based therapies are a novel approach within precision medicine that have demonstrated success, particularly in rare diseases. Three antisense oligonucleotides (AONs) are currently in development for the treatment of specific IRD subtypes. These RNA-based therapies bring several key advantages in the setting of IRDs, and the potential to bring meaningful vision benefit to individuals living with inherited blinding disorders. This review will examine the increasing breadth and relevance of RNA-based therapies in clinical medicine, explore the key features that make AONs suitable for treating genetic eye diseases, and provide an overview of the three-leading investigational AONs in clinical trials.

At preterm birth, the retina is incompletely vascularized. Retinopathy of prematurity (ROP) is initiated by the postnatal suppression of physiological retinal vascular development that would normally occur in utero. As the neural retina slowly matures, increasing metabolic demand including in the peripheral avascular retina, leads to signals for compensatory but pathological neovascularization. Currently, only late neovascular ROP is treated. ROP could be prevented by promoting normal vascular growth. Early perinatal metabolic dysregulation is a strong but understudied risk factor for ROP and other long-term sequelae of preterm birth. We will discuss the metabolic and oxygen needs of retina, current treatments, and potential interventions to promote normal vessel growth including control of postnatal hyperglycemia, dyslipidemia and hyperoxia-induced retinal metabolic alterations. Early supplementation of missing nutrients and growth factors and control of supplemental oxygen promotes physiological retinal development. We will discuss the current knowledge gap in retinal metabolism after preterm birth.