Deborah M. Costakos

Retinopathy of Prematurity (ROP) affects preterm infants worldwide, involving abnormal development of retinal blood vessels associated with supplemental oxygen use in neonatal care. Although there have been strides in identifying at-risk infants, implementing early screening, updating disease criteria through the International Classification of Retinopathy of Prematurity (ICROP), and developing new therapies, ROP remains a leading cause of preventable blindness. As preterm birth survival rates rise, the incidence of ROP continues to increase and is projected to rise even in countries with abundant resources and well-established care programs. Improving ROP care requires global standardization of screening, diagnosis, and management to prevent missed diagnoses and minimize outcome variability. Intravitreal anti-vascular endothelial growth factor (VEGF) injections are changing the landscape of ROP management, but longitudinal research is needed to determine their long-term safety in preterm infants. Effective ROP management relies on teamwork across disciplines and open communication with parents. Given that parents are lifelong caregivers of a child who may be affected by ROP-related vision impairment, including them in the care team and encouraging psychosocial support is vital. Socioeconomic disparities and limited access to ROP-trained ophthalmologists exacerbate disease burden, underscoring the need for innovative solutions to improve access to care. This perspective emphasizes the importance of globally standardizing ROP prevention and care, noting that efforts are still incomplete, equitable access has not been realized, and the long-term role of anti-VEGF agents in ROP treatment remains unclear.

Diabetic retinopathy (DR) is a microvascular complication of diabetes in the retina. Chronic hyperglycemia damages retinal microvasculature embedded into the extracellular matrix (ECM), causing fluid leakage and ischemic retinal neovascularization. Current treatment strategies include intravitreal anti-vascular endothelial growth factor (VEGF) or steroidal injections, laser photocoagulation, or vitrectomy in severe cases. However, treatment may require multiple modalities or repeat treatments due to variable response. Though DR management has achieved great success, improved, long-lasting, and predictable treatments are needed, including new biomarkers and therapeutic approaches. Small-leucine rich proteoglycans, such as decorin, constitute an integral component of retinal endothelial ECM. Therefore, any damage to microvasculature can trigger its antifibrotic and antiangiogenic response against retinal vascular pathologies, including DR. We conducted a cross-sectional study to examine the association between aqueous humor (AH) decorin levels, if any, and severity of DR. A total of 82 subjects (26 control, 56 DR) were recruited. AH was collected and decorin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). Decorin was significantly increased in the AH of DR subjects compared to controls (p = 0.0034). AH decorin levels were increased in severe DR groups in ETDRS and Gloucestershire classifications. Decorin concentrations also displayed a significant association with visual acuity (LogMAR) measurements. In conclusion, aqueous humor decorin concentrations were found elevated in DR subjects, possibly due to a compensatory response to the retinal microvascular changes during hyperglycemia.

Retinal diseases such as age-related macular degeneration (AMD), retinopathy of prematurity (ROP), and diabetic retinopathy (DR) are the leading causes of visual impairment worldwide. There is a critical need to understand the structural and cellular components that play a vital role in the pathophysiology of retinal diseases. One potential component is the family of structural proteins called small leucine-rich proteoglycans (SLRPs). SLRPs are crucial in many fundamental biological processes involved in the maintenance of retinal homeostasis. They are present within the extracellular matrix (ECM) of connective and vascular tissues and contribute to tissue organization and modulation of cell growth. They play a vital role in cell–matrix interactions in many upstream signaling pathways involved in fibrillogenesis and angiogenesis. In this comprehensive review, we describe the expression patterns and function of SLRPs in the retina, including Biglycan and Decorin from class I; Fibromodulin, Lumican, and a Proline/arginine-rich end leucine-rich repeat protein (PRELP) from class II; Opticin and Osteoglycin/Mimecan from class III; and Chondroadherin (CHAD), Tsukushi and Nyctalopin from class IV.

Purpose Formalized handoff procedures have been shown to increase patient safety and quality of care across multiple medical and surgical specialties,^1–4 but literature regarding handoffs in ophthalmology remains sparse. We instituted a standardized handoff utilizing an electronic medical record (EMR) system to improve care for patients shared by multiple resident physicians across weekday, weeknight, and weekend duty shifts. We measured efficiency, efficacy, and resident satisfaction before and after the standardized handoff was implemented. Methods Resident physicians surveyed were primarily responsible for patient care on consult and call services at two quaternary academic medical centers in a major metropolitan area. Patient care was performed in outpatient, emergency, and inpatient settings. Annual anonymous questionnaires consisting of 6 questions were used to collect pre- and postintervention impressions of the standardized EMR handoff process from ophthalmology resident physicians (9 per year; 3 preintervention years and 1 postintervention year). An additional anonymous postintervention questionnaire consisting of 12 questions was used to further characterize resident response to the newly implemented handoff procedure. Results Prior to implementation of a standardized EMR-based handoff procedure, residents unanimously reported incomplete, infrequently updated handoff reports that did not include important clinical and/or psychosocial information. Following implementation, residents reported a statistically significant increase in completeness and timeliness of handoff reports. Additionally, resident perception of EMR handoff utility, efficiency, and usability were comprehensively favorable. Residents reported handoffs only added a mean of 6.5 minutes to a typical duty shift. Conclusion Implementation of our protocol dramatically improved resident perceptions of the handoff process at our institution. Improvements included increased quality, ease-of-use, and efficiency. Our standardized EMR-based handoff procedure may be of use to other ambulatory-based services. Received: 03 August 2020 Accepted: 31 August 2020 Publication Date: 30 October 2020 (online) © 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

BACKGROUND AND OBJECTIVE: To determine whether retinopathy of prematurity (ROP) that persists beyond a postmenstrual age (PMA) of 45 weeks has abnormalities that can be documented by fundus photography or fluorescein angiography (FA). PATIENTS AND METHODS: Fundus photographs and FAs were reviewed for all premature infants who underwent FA for persistent ROP after 45 weeks PMA. RESULTS: Of the 487 infants who were screened for ROP, 16 (3.3%) demonstrated ROP beyond 45 weeks. Seven (43.8%) infants received prior treatment with intravitreal bevacizumab (IVB) for Type 1 ROP. FAs were obtained in eight cases; four subjects were previously treated with IVB. Leakage at the vascular-avascular border was demonstrated in seven subjects (87.5%). Shunt vessels, posterior retinal nonperfusion, and absence of the foveal avascular zone was limited to the IVB group. CONCLUSIONS: There are persistent vascular abnormalities among infants with ROP beyond 45 weeks. Findings that may be missed by RetCam fundus photographs were highlighted with FA. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:497–503.]

Congenital cataracts affect 3–6 per 10,000 live births and represent one of the leading causes of blindness in children. Congenital cataracts have a strong genetic component with high heterogeneity and variability. Analysis of whole exome sequencing data in a patient affected with congenital cataracts identified a pathogenic deletion which was further defined by other techniques. A ~98-kb homozygous deletion of 6p24.3 involving the first three exons (two non-coding and one coding) of GCNT2 isoform A, the first exon (coding) of GCNT2 isoform B, and part of the intergenic region between GCNT2 and TFAP2A was identified in the patient and her brother while both parents were found to be heterozygous carriers of the deletion. The exact breakpoints were identified and revealed the presence of Alu elements at both sides of the deletion, thus indicating Alu-mediated non-homologous end-joining as the most plausible mechanism for this rearrangement. Recessive mutations in GCNT2 are known to cause an adult i blood group phenotype with congenital cataracts in some cases. The GCNT2 gene has three differentially expressed transcripts, with GCNT2B being the only isoform associated with lens function and GCNT2C being the only isoform expressed in red blood cells based on earlier studies; previously reported mutations/deletions have either affected all three isoforms (causing blood group and cataract phenotype) or the C isoform only (causing blood group phenotype only). Dominant mutations in TFAP2A are associated with syndromic anophthalmia/microphthalmia and other ocular phenotypes as part of Branchio-Ocular-Facial-Syndrome (BOFS). While the patients do not fit a diagnosis of BOFS, one sibling demonstrates mild overlap with the phenotypic spectrum, and therefore an effect of this deletion on the function of TFAP2A cannot be ruled out. To the best of our knowledge, this is the first case reported in which disruption of the GCNT2 gene does not involve the C isoform. The congenital cataracts phenotype in the affected patients is consistent with the previously defined isoform-specific roles of this gene. The GCNT2-TFAP2A region may be prone to rearrangements through Alu-mediated non-homologous end-joining.