The Continuing Impact of the COVID-19 Pandemic on Diabetic Retinopathy Screenings.

PURPOSE: This retrospective observational study of health claims data seeks to quantify the prolonged impact of the COVID-19 pandemic on DR screening rates in central Massachusetts. METHODS: Retrospective claims data from the UMass Memorial Managed Care Network were collected for the years of 2018-2022. Comprehensive and DR screening exams were identified using CPT codes for patients with diabetes. Data were derived from claims submitted by the UMass Memorial Managed Care network to four insurance programs via CPT billing code for comprehensive and DR screening exams for patients with diabetes. Over one million claims for the years 01/2018-05/2022 were collected. RESULTS: We found a significant decrease in unadjusted DR screening rates in the post-lockdown period compared to the pre-COVID-19 period (p < 0.001). Bivariate analysis revealed a 15.1% decrease in weekly DR screenings during post-lockdown (RR = 0.849, 95% CI = 0.811, 0.888). After adjusting for seasonal variation, the mean weekly DR screening rate was 12% lower in the post-lockdown period, with a 95% CI of 6.1% to 17.5% decrease (Adjusted RR = 0.880, 95% CI = 0.825, 0.939 Stratified analysis based on patient status revealed a significant decrease in adjusted DR screening rates for established patients post-lockdown compared to pre-pandemic (p < 0.0001), while no significant difference was observed for new patients (p > 0.05). CONCLUSION: The impact of COVID-19 on DR screening and treatment rates persisted even after the resumption of non-essential care services, with a discrepancy between new and established patients. Future research should work to identify and overcome the barriers to DR screening.

Ocular immunosuppressive microenvironment and novel drug delivery for control of uveitis.

Ocular immune privilege is a phenomenon described by Peter Medawar in relation to the indefinite survival of the placement of foreign tissue grafts into the eye. Several mechanisms have been described that contribute to ocular immune privilege, such as a blood-ocular barrier and lack of lymphatics in the eye, the production of immune-suppressing molecules inside the ocular microenvironment, and the induction of systemic regulatory immunity against antigens found in the eye. Because ocular immune privilege is not absolute, failure of it can result in uveitis. Uveitis is a group of inflammatory disorders that can lead to vision loss if not treated properly. The current uveitis treatments involve the use of immunosuppressive and anti-inflammatory medications. Researching mechanisms of ocular immune privilege and the development of novel treatments for uveitis is ongoing. This review discusses mechanisms of ocular immune privilege, followed by an overview of uveitis treatments and ongoing clinical trials.

Prenatal phenotype analysis and mutation identification of a fetus with meckel gruber syndrome.

Ciliopathies are a class of inherited severe human disorders that occur due to defective formation or function of cilia. The RPGRIP1L (retinitis pigmentosa GTPase regulator-interacting protein1-like) gene encodes for a ciliary protein involved in regulating cilia formation and function. Mutations in RPGRIP1L cause ciliopathies associated with severe embryonic defects, such as Meckel-Gruber Syndrome (MKS). Here we report RPGRIP1L mutation analysis in a family diagnosed with MKS. The clinical manifestations of the fetus included thoraco-lumbar open neural tube defect with associated Chiari type II malformation and hydrocephalus, bilateral club feet, and single right kidney/ureter. Analysis of the parental DNA samples revealed that the father carried a previously reported mutation R1236C/+ whereas the mother had a novel splice site mutation IVS6+1 G > A/+ in RPGRIP1L. The splice site mutation resulted in the exclusion of in-frame exon 6 of RPGRIP1L (RPGRIP1L-∆Ex6) but expressed a stable protein in fibroblasts derived from the parents' skin biopsies. The GFP-RPGRIP1L-∆Ex6 mutant protein exhibited relatively reduced ciliary localization in transiently-transfected cultured RPE-1 cells. Taken together, this study identifies a novel RPGRIP1L variant RPGRIP1L-∆Ex6, which in combination with RPGRIP1L-R1236C is associated with MKS. We also suggest that the deletion of exon 6 of RPGRIP1L leads to reduced ciliary localization of RPGRIP1L, indicating a plausible mechanism of associated disease.

Ocular Drug Delivery: Advancements and Innovations.

Ocular drug delivery has been significantly advanced for not only pharmaceutical compounds, such as steroids, nonsteroidal anti-inflammatory drugs, immune modulators, antibiotics, and so forth, but also for the rapidly progressed gene therapy products. For conventional non-gene therapy drugs, appropriate surgical approaches and releasing systems are the main deliberation to achieve adequate treatment outcomes, whereas the scope of "drug delivery" for gene therapy drugs further expands to transgene construct optimization, vector selection, and vector engineering. The eye is the particularly well-suited organ as the gene therapy target, owing to multiple advantages. In this review, we will delve into three main aspects of ocular drug delivery for both conventional drugs and adeno-associated virus (AAV)-based gene therapy products: (1) the development of AAV vector systems for ocular gene therapy, (2) the innovative carriers of medication, and (3) administration routes progression.