Classification and Growth Rate of Chorioretinal Atrophy after Voretigene Neparvovec-Rzyl for RPE65-Mediated Retinal Degeneration.

PURPOSE: Classify the appearance and quantify the growth rate of chorioretinal atrophy in patients who received voretigene neparvovec-rzyl (VN) for RPE65-mediated retinal degeneration. DESIGN: Multicenter retrospective analysis. SUBJECTS: Patients who underwent subretinal VN injection at 5 institutions and demonstrated posterior-pole chorioretinal atrophy. METHODS: Ultrawidefield scanning laser ophthalmoscopy or color fundus photos were assessed before and after subretinal VN. Atrophy was defined as regions with ≥ 2 of the following: (1) partial or complete retinal pigment epithelial depigmentation; (2) round shape; (3) sharp margins; and (4) increased visibility of choroidal vessels. Atrophy was qualitatively classified into different subtypes. All atrophy was manually segmented. Linear mixed-effects models with random slopes and intercepts were fit using atrophy area and square root of atrophy area. MAIN OUTCOME MEASURES: Number of eyes with each atrophy pattern, and slopes of linear mixed-effects models. RESULTS: Twenty-seven eyes from 14 patients across 5 centers developed chorioretinal atrophy after subretinal VN. A mean of 5.8 ± 2.7 images per eye obtained over 2.2 ± 0.8 years were reviewed, and atrophy was categorized into touchdown (14 eyes), nummular (15 eyes), and perifoveal (12 eyes) subtypes. Fifteen eyes demonstrated > 1 type of atrophy. Thirteen of 14 patients demonstrated bilateral atrophy. The slopes of the mixed-effects models of atrophy area and square root of atrophy area (estimate ± standard error) were 1.7 ± 1.3 mm2/year and 0.6 ± 0.2 mm/year for touchdown atrophy, 5.5 ± 1.3 mm2/year and 1.2 ± 0.2 mm/year for nummular atrophy, and 16.7 ± 1.8 mm2/year and 2.3 ± 0.2 mm/year for perifoveal atrophy. The slopes for each type of atrophy were significantly different in the square root of atrophy model, which best fit the data (P < 0.05). CONCLUSIONS: Chorioretinal atrophy after subretinal VN for RPE65-mediated retinal degeneration developed according to a touchdown, nummular, and/or perifoveal pattern. Perifoveal atrophy grew the most rapidly, while touchdown atrophy grew the least rapidly. Understanding the causes of these findings, which are present in a minority of patients, merits further investigation. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Risk Factors Associated with Cystoid Macular Edema among Patients Undergoing Primary Repair of Rhegmatogenous Retinal Detachment.

PURPOSE: To investigate predictors of the development and resolution of cystoid macular edema (CME) after rhegmatogenous retinal detachment (RRD) repair. DESIGN: Retrospective cross sectional study. SUBJECTS: Patients who underwent primary repair of uncomplicated RRD. METHODS: Demographics, ophthalmic history, visual acuity, RRD features, time to development/resolution of CME, OCT characteristics of CME/epiretinal membrane (ERM), type of surgery, and treatments were collected. Logistic regressions were used to identify predictors of CME development and resolution. MAIN OUTCOME MEASURES: Predictors of CME development and resolution. RESULTS: A total of 708 eyes were included, of which 55 (7.8%) developed CME. Factors associated with an increased risk of CME development included total number of retinal detachment surgeries (odds ratio [OR] 1.66 [1.24-2.23], P < 0.001), prior intraocular surgery (OR 4.43 [1.19-16.51], P = 0.03), and presence of ERM after surgery (OR 4.49 [2.30-8.74], P < 0.001). Patients undergoing pars plana vitrectomy (PPV) were more likely to develop CME compared with patients undergoing scleral buckling (SB; OR 3.09 [1.18-8.10], P = 0.02). A longer average time to CME detection was associated with lower CME resolution (OR 0.94 [0.89-0.998], P = 0.04). In patients who developed an ERM postsurgically, those who developed CME after ERM had a lower rate of resolution compared with those who developed CME before ERM (P = 0.03). CONCLUSIONS: Cystoid macular edema may be more likely to develop in patients undergoing PPV than SB, those who underwent more surgeries for RRD repair, those who had prior intraocular surgery, or those who developed an ERM after RRD repair. Resolution of CME may be affected by the time to detection of CME and ERM development. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Application of a life table approach to assess duration of BNT162b2 vaccine-derived immunity by age using COVID-19 case surveillance data during the Omicron variant period.

BACKGROUND: SARS-CoV-2 Omicron variants have the potential to impact vaccine effectiveness and duration of vaccine-derived immunity. We analyzed U.S. multi-jurisdictional COVID-19 vaccine breakthrough surveillance data to examine potential waning of protection against SARS-CoV-2 infection for the Pfizer-BioNTech (BNT162b) primary vaccination series by age. METHODS: Weekly numbers of SARS-CoV-2 infections during January 16, 2022-May 28, 2022 were analyzed by age group from 22 U.S. jurisdictions that routinely linked COVID-19 case surveillance and immunization data. A life table approach incorporating line-listed and aggregated COVID-19 case datasets with vaccine administration and U.S. Census data was used to estimate hazard rates of SARS-CoV-2 infections, hazard rate ratios (HRR) and percent reductions in hazard rate comparing unvaccinated people to people vaccinated with a Pfizer-BioNTech primary series only, by age group and time since vaccination. RESULTS: The percent reduction in hazard rates for persons 2 weeks after vaccination with a Pfizer-BioNTech primary series compared with unvaccinated persons was lowest among children aged 5-11 years at 35.5% (95% CI: 33.3%, 37.6%) compared to the older age groups, which ranged from 68.7%-89.6%. By 19 weeks after vaccination, all age groups showed decreases in the percent reduction in the hazard rates compared with unvaccinated people; with the largest declines observed among those aged 5-11 and 12-17 years and more modest declines observed among those 18 years and older. CONCLUSIONS: The decline in vaccine protection against SARS-CoV-2 infection observed in this study is consistent with other studies and demonstrates that national case surveillance data were useful for assessing early signals in age-specific waning of vaccine protection during the initial period of SARS-CoV-2 Omicron variant predominance. The potential for waning immunity during the Omicron period emphasizes the importance of continued monitoring and consideration of optimal timing and provision of booster doses in the future.

Outbreaks of SARS-CoV-2 Infections in Nursing Homes during Periods of Delta and Omicron Predominance, United States, July 2021-March 2022.

SARS-CoV-2 infections among vaccinated nursing home residents increased after the Omicron variant emerged. Data on booster dose effectiveness in this population are limited. During July 2021-March 2022, nursing home outbreaks in 11 US jurisdictions involving >3 infections within 14 days among residents who had received at least the primary COVID-19 vaccine(s) were monitored. Among 2,188 nursing homes, 1,247 outbreaks were reported in the periods of Delta (n = 356, 29%), mixed Delta/Omicron (n = 354, 28%), and Omicron (n = 536, 43%) predominance. During the Omicron-predominant period, the risk for infection within 14 days of an outbreak start was lower among boosted residents than among residents who had received the primary vaccine series alone (risk ratio [RR] 0.25, 95% CI 0.19-0.33). Once infected, boosted residents were at lower risk for all-cause hospitalization (RR 0.48, 95% CI 0.40-0.49) and death (RR 0.45, 95% CI 0.34-0.59) than primary vaccine-only residents.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) outbreaks in nursing homes involving residents who had completed a primary coronavirus disease 2019 (COVID-19) vaccine series-13 US jurisdictions, July-November 2021.

Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents.

Management of uncomplicated rhegmatogenous retinal detachments: a comparison of practice patterns and clinical outcomes in a real-world setting.

OBJECTIVE: To investigate practice patterns and clinical outcomes in the repair of uncomplicated rhegmatogenous retinal detachments (RRD) in a real-world setting over a 10-year period. METHODS: We compared preferences for scleral buckling (SB), pars plana vitrectomy (PPV), PPV/SB, or pneumatic retinopexy (PR) over time, and examined the 1-year single surgery anatomic success (SSAS) and best-corrected visual acuity (BCVA) at a tertiary academic institution from 2008-2018. RESULTS: Eight hundred eight eyes had RRD repair between 2008-2011 (n = 240), 2012-2014 (n = 271), and 2015-2017 (n = 297). Compared to 2008-2011, PPV was preferred over SB in 2012-2014 (OR: 2.93; 95% CI: 1.86-4.63) and 2015-2017 (OR: 5.94; 95% CI: 3.76-9.38), and over PPV/SB in 2012-2014 (OR: 2.74; 95% CI: 1.65-4.56) and 2015-2017 (OR: 3.16; 95% CI: 31.96-5.12). PR was uncommonly utilized (<10%). Younger surgeons (graduating 2010-2017) favored PPV over SB when compared to older surgeons [graduating 1984-2000 (OR: 1.77; 95% CI: 1.18-2.65) and 2001-2009 (OR 1.73; 95% CI: 1.14-2.65)], but similarly selected PPV vs. PPV/SB as their older counterparts (p > 0.05). Compared to PPV, SSAS was higher with SB (OR: 1.53; 95% CI: 1.03-2.26) and PPV/SB (OR: 2.55; 95% CI: 1.56-4.17). One-year BCVA was markedly improved compared to baseline only for eyes that achieved SSAS (p < 0.001). CONCLUSIONS: Over the past 10 years, PPV has become the favored approach to repair uncomplicated RRD and this appears to be driven by younger surgeons' preferences. Given the superior long-term SSAS in SB and PPV/SB as compared to PPV, SB and PPV/SB should be more frequently considered when determining the appropriate repair strategy for uncomplicated RRD.

Characteristics of nursing home residents and healthcare personnel with repeated severe acute respiratory coronavirus virus 2 (SARS-CoV-2) tests positive ≥90 days after initial infection: Four US jurisdictions, July 2020-March 2021.

One in six nursing home residents and staff with positive SARS-CoV-2 tests ≥90 days after initial infection had specimen cycle thresholds (Ct) <30. Individuals with specimen Ct<30 were more likely to report symptoms but were not different from individuals with high Ct value specimens by other clinical and testing data.

Global Disparities in Retinopathy of Prematurity: A Literature Review.

PURPOSE: To provide an overview of the impact of retinopathy of prematurity (ROP), and the challenges in the screening, diagnosis, and treatment of ROP worldwide. METHODS: A comprehensive search was conducted using the PubMed database from January 2011 to October 2021 using the following keywords: retinopathy of prematurity, laser, and anti-vascular endothelial growth factor (VEGF). Data on patient characteristics, ROP treatment type, and recurrence rates were collected. The countries included in these studies were classified based on 2021-2022 World Bank definitions of high, upper-middle, lower-middle, and low-income groups. Moreover, a search for surgical outcomes for ROP and screening algorithms and artificial intelligence for ROP was conducted. RESULTS: Thirty-nine studies met the inclusion criteria. ROP treatment and outcomes showed a trend towards intravitreal anti-VEGF injections as the initial treatment for ROP globally and the treatment of recurrent ROP in high-income countries. However, laser remains the treatment of choice for ROP recurrence in middle-income countries. Surgical outcomes for ROP stage 4A, 4B and 5 are similar worldwide. The incidence of ROP and ROP-related visual impairment continue to increase globally. Although telemedicine and artificial intelligence offer potential solutions to ROP screening in resource-limited areas, the current models require further optimization to reflect the global diversity of ROP patients. CONCLUSION: ROP screening and treatment paradigms vary widely based on country income group due to disparities in resources, limited access to care, and lack of universal guidelines.

Combined Therapeutic Penetrating Keratoplasty and Pars Plana Vitrectomy for the Treatment of Infectious Keratitis Endophthalmitis: Mexican Endophthalmitis Study Group Protocol 4.

PURPOSE: The purpose of this study was to assess the role of combined surgical treatment of therapeutic penetrating keratoplasty and pars plana vitrectomy in the anatomical and functional outcome of infectious keratitis endophthalmitis. METHODS: This study reviewed the medical records of 4 participating centers in the United States and Mexico. This study included patients with a clinical diagnosis of infectious keratitis endophthalmitis who had been treated with an early therapeutic penetrating keratoplasty and pars plana vitrectomy as the main treatment for endophthalmitis. From each medical record, the study retrieved demographic data, relevant medical and drug history, baseline clinical manifestation of endophthalmitis, best-corrected visual acuity, and the need for enucleation/evisceration for the control of the infection or any other reason through the follow-up. RESULTS: The study included 48 patients (50.15 ± 20.6 years). The mean follow-up time was 13 ± 0.5 months. The mean best-corrected visual acuity at baseline was 2.1 ± 0.25 logarithm of the minimum angle of resolution. At month 12 was 2.09 ± 0.61 logarithm of the minimum angle of resolution ( P = 0.9). The overall prevalence of enucleation/evisceration was 8.3% (95% confidence interval: 2.32%-19.98%). The prevalence of a vision of no-light perception was 20.8% (95% confidence interval: 2.32%-19.98%). CONCLUSIONS: Combined surgery for severe cases of infectious keratitis endophthalmitis eradicates the infection in most cases, while significantly improving the overall outcomes.

Socioeconomic disadvantage and impact on visual outcomes in patients with viral retinitis and retinal detachment.

While socioeconomic disparities impact clinical care and patient outcomes, their impact on the anatomic and visual outcomes of retinal detachment in patients with viral retinitis is unstudied. This case series included 18 eyes in 18 patients from a single academic institution between January 1, 2008 and December 31, 2018. Patient characteristics including age, sex, race, ethnicity, insurance, immunosuppression, viral retinitis, retinal detachment, retinal detachment repair, visual and anatomic outcomes, missed appointments, and Area Deprivation Index [ADI] were collected. The low-ADI group, indicating less socioeconomic disadvantage, was comprised of twelve patients with national ADIs less than 38, and the high-ADI group of six patients with national ADIs greater than 38. High-ADI patients tended to be younger (average age 38.0 versus 51.3; P = 0.06), of female sex (P = 0.03), and had more missed appointments (median 11.0 vs 0; P = 0.002). A similar number of patients in both the high-ADI and low-ADI groups underwent pars plana vitrectomy alone or pars plana vitrectomy with scleral buckle. Visual acuity was similar in the high-ADI group than in the low-ADI group at baseline, but worse at the final follow-up visit (P = 0.004). Post-operative and final visit ocular hypotony were more common in the high-ADI group (P = 0.02). In our series, socioeconomic disadvantage negatively affects the visual outcomes in patients with viral retinitis associated-retinal detachments. These factors should be considered by ophthalmologists when treating these patients.

Vitrectomy versus Vitrectomy with Scleral Buckling in the Treatment of Giant Retinal Tear Related Retinal Detachments: An International Multicenter Study.

PURPOSE: To determine the practice pattern for treating giant retinal tear (GRT) related detachments, and their anatomic and visual outcomes with pars plana vitrectomy (PPV) with or without scleral buckling (SB). DESIGN: Retrospective cohort study. SUBJECTS: Eyes with GRT detachments repaired from 2008 to 2020 with at least 6 months of follow-up from 7 institutions in North and South America, Europe, and Asia. METHODS: Eyes repaired using PPV versus PPV/SB were compared. MAIN OUTCOME MEASURES: Anatomic and functional outcomes. RESULTS: A comparable number of eyes underwent PPV (n = 101) and PPV/SB (n = 99). Except for history of developmental abnormalities, prior intraocular surgery, and lens status, no differences in baseline demographics, ocular characteristics, or intraoperative surgical adjuncts were observed. The overall single surgery anatomic success (SSAS) at 6 months and 1 year were similar between the groups (82.2% and 77.2% of PPV, and 87.9% and 85.7% of PPV/SB). When stratified by age, the 1-year SSAS rate was higher for PPV/SB (88.5%) than PPV (56.3%) (P = 0.03) for children <18 years. For both children and adults, the mean best-corrected visual acuity (BCVA) at baseline did not differ between the PPV and PPV/SB groups. However, for children, mean BCVA at 1 year was better in the PPV/SB than PPV groups (P = 0.001) while for adults, no difference was found between the 2 groups. The mean time to the first redetachment was 7.9 months in the PPV group and 5.5 months in the PPV/SB group (P = 0.8). Proliferative vitreoretinopathy was the most common cause for redetachment (70.4% of PPV and 93.8% of PPV/SB in redetached eyes; P = 0.1). Postoperative complications were also similar between the 2 groups, including ocular hypertension, epiretinal membrane, and cataract formation. CONCLUSIONS: PPV and PPV/SB are equally popular among surgeons globally for managing GRT detachments and have comparable anatomic and visual outcomes in adults. In children, PPV/SB is superior to PPV for anatomic and functional success at 1 year. In adults, the relief of traction by the GRT may reduce peripheral traction and obviate the need for an SB. However, in children, a supplemental SB can be beneficial as complete vitreous shaving and posterior hyaloid detachment, and postoperative positioning, are difficult in this group.

COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence - 25 U.S. Jurisdictions, April 4-December 25, 2021.

Previous reports of COVID-19 case, hospitalization, and death rates by vaccination status† indicate that vaccine protection against infection, as well as serious COVID-19 illness for some groups, declined with the emergence of the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, and waning of vaccine-induced immunity (1-4). During August-November 2021, CDC recommended§ additional primary COVID-19 vaccine doses among immunocompromised persons and booster doses among persons aged ≥18 years (5). The SARS-CoV-2 B.1.1.529 (Omicron) variant emerged in the United States during December 2021 (6) and by December 25 accounted for 72% of sequenced lineages (7). To assess the impact of full vaccination with additional and booster doses (booster doses),¶ case and death rates and incidence rate ratios (IRRs) were estimated among unvaccinated and fully vaccinated adults by receipt of booster doses during pre-Delta (April-May 2021), Delta emergence (June 2021), Delta predominance (July-November 2021), and Omicron emergence (December 2021) periods in the United States. During 2021, averaged weekly, age-standardized case IRRs among unvaccinated persons compared with fully vaccinated persons decreased from 13.9 pre-Delta to 8.7 as Delta emerged, and to 5.1 during the period of Delta predominance. During October-November, unvaccinated persons had 13.9 and 53.2 times the risks for infection and COVID-19-associated death, respectively, compared with fully vaccinated persons who received booster doses, and 4.0 and 12.7 times the risks compared with fully vaccinated persons without booster doses. When the Omicron variant emerged during December 2021, case IRRs decreased to 4.9 for fully vaccinated persons with booster doses and 2.8 for those without booster doses, relative to October-November 2021. The highest impact of booster doses against infection and death compared with full vaccination without booster doses was recorded among persons aged 50-64 and ≥65 years. Eligible persons should stay up to date with COVID-19 vaccinations.

Covid-19 Rates by Time since Vaccination during Delta Variant Predominance.

BACKGROUND: With the emergence of the delta variant, the United States experienced a rapid increase in Covid-19 cases in 2021. We estimated the risk of breakthrough infection and death by month of vaccination as a proxy for waning immunity during a period of delta variant predominance. METHODS: Covid-19 case and death data from 15 U.S. jurisdictions during January 3 to September 4, 2021 were used to estimate weekly hazard rates among fully vaccinated persons, stratified by age group and vaccine product. Case and death rates during August 1 to September 4, 2021 were presented across four cohorts defined by month of vaccination. Poisson models were used to estimate adjusted rate ratios comparing the earlier cohorts to July rates. RESULTS: During August 1 to September 4, 2021, case rates per 100,000 person-weeks among all vaccine recipients for the January to February, March to April, May to June, and July cohorts were 168.8 (95% confidence interval [CI], 167.5 to 170.1), 123.5 (95% CI, 122.8 to 124.1), 83.6 (95% CI, 82.9 to 84.3), and 63.1 (95% CI, 61.6 to 64.6), respectively. Similar trends were observed by age group for BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccine recipients. Rates for the Ad26.COV2.S (Janssen-Johnson & Johnson) vaccine were higher; however, trends were inconsistent. BNT162b2 vaccine recipients 65 years of age or older had higher death rates among those vaccinated earlier in the year. Protection against death was sustained for the mRNA-1273 vaccine recipients. Across age groups and vaccine types, people who were vaccinated 6 months ago or longer (January-February) were 3.44 (3.36 to 3.53) times more likely to be infected and 1.70 (1.29 to 2.23) times more likely to die from COVID-19 than people vaccinated recently in July 2021. CONCLUSIONS: Our study suggests that protection from SARS-CoV-2 infection among all ages or death among older adults waned with increasing time since vaccination during a period of delta predominance. These results add to the evidence base that supports U.S. booster recommendations, especially for older adults vaccinated with BNT162b2 and recipients of the Ad26.COV2.S vaccine. (Funded by the Centers for Disease Control and Prevention.).

Nonmydriatic Ultra-Widefield Fundus Photography in a Hematology Clinic Shows Utility for Screening of Sickle Cell Retinopathy.

PURPOSE: To determine the feasibility and accuracy of nonmydriatic ultra-widefield (UWF) fundus photographs taken in a hematology clinic setting for screening of sickle cell retinopathy (SCR) DESIGN: Prospective cohort study. METHODS: This single-site study took place at the Johns Hopkins Sickle Cell Center for Adults and the Wilmer Eye Institute. The study population was 90 eyes of 46 consecutive adults with sickle cell disease (SCD). Bilateral nonmydriatic fundus photos taken by clinic personnel during the participants' routine hematology appointment were graded by 2 masked retina specialists at the Wilmer Eye Institute for the presence of nonproliferative SCR (NPSR) and proliferative sickle retinopathy (PSR). A third retina specialist adjudicated in cases of grader disagreement. All participants underwent the standard dilated fundus examination (DFE) within 2 years of acquisition of UWF photographs. The main outcome measure was the sensitivity and specificity of nonmydriatic UWF images for the detection of NPSR and PSR RESULTS: PSR was noted in 19 of 90 eyes that underwent DFE and in 9 of 67 gradable UWF images. Interrater agreement between the 2 graders was moderate, with κ = 0.65 (range 0.43-0.87) for PSR. For gradable UWF photos, the sensitivity and specificity of detecting SCR using the nonmydriatic photos compared with the DFE were 85.2% and 62.5% for NPSR, respectively, and 69.2% and 100% for detection of PSR, respectively. One participant required ophthalmic therapy in both eyes for active sea-fan neovascularization. CONCLUSIONS: UWF imaging shows utility in screening for SCR and may help identify patients with PSR who require a DFE and who may benefit from treatment.

Repair of progressive retinal detachment complicating degenerative retinoschisis: surgical management and outcomes in phakic eyes.

BACKGROUND: Degenerative retinoschisis is a common condition defined by the splitting of the neurosensory retina that may rarely be associated with progressive retinal detachment (RD). Here, we aim to describe the anatomic and functional outcomes of surgical treatment of progressive symptomatic retinal detachment complicating degenerative retinoschisis (PSRDCR) using pars plana vitrectomy (PPV), scleral buckle (SB), or combined PPV/SB procedure. METHODS: A retrospective chart review of patients with PSRDCR between Jan 1, 2008 and Dec 31, 2019 was conducted. Data regarding demographics, surgical approach, and anatomic/functional outcomes were collected. RESULTS: Of the 4973 charts with RD repair during the study period, 36 eyes (0.7%) had retinoschisis with RD. 18 eyes met inclusion criteria (0.4%). The median age was 54 years (range 18-74) and all eyes were phakic. All eyes had outer layer breaks (OLBs) and 16 eyes (89%) had identifiable inner layer breaks. All OLBs were posterior to the equator in charts where position was recorded (16 eyes). The single surgery anatomic success (SSAS) and final anatomical success rates were 66% (12/18) and 100%, respectively. Eyes treated with PPV/SB had an SSAS rate of 75% (9/12), while PPV and SB had SSAS rates of 66% (2/3) and 33% (1/3), respectively. CONCLUSIONS: PSRDCR is an exceedingly rare complication of degenerative retinoschisis associated with an SSAS rate lower than for uncomplicated rhegmatogenous RD. The majority of PSRDCR were repaired via combined PPV/SB in our study, and the rarity of this complication limits statistical support of an optimal surgical method in our and prior studies. The role of SB combined with PPV for PSRDCR requires further investigation.

The Impact of COVID-19 on Diabetic Retinopathy Monitoring and Treatment.

PURPOSE OF REVIEW: Diabetic retinopathy (DR) is one of the leading causes of vision loss worldwide. Although screening and early treatment guidelines for DR have significantly reduced the disease burden, restrictions related to the COVID-19 pandemic have changed real-world practice patterns in the management of DR. This review summarizes evolving guidelines and outcomes of the treatment of DR in the setting of the pandemic. RECENT FINDINGS: Intravitreal injections for DR have decreased significantly globally during the pandemic, ranging from approximately 30 to nearly 100% reduction, compared to corresponding timepoints in 2019. Most studies on functional outcomes show a decrease in visual acuity on delayed follow-up. Changing practice patterns in the management of DR has led to fewer intravitreal injections and overall reduction in visual acuity on follow-up. As COVID variants emerge, it will be necessary to continue evaluating practice guidelines.

Pluripotent stem cell therapy for retinal diseases.

Pluripotent stem cells (PSCs), which include human embryonic stem cells (hESCs) and induced pluripotent stem cell (iPSC), have been used to study development of disease processes, and as potential therapies in multiple organ systems. In recent years, there has been increasing interest in the use of PSC-based transplantation to treat disorders of the retina in which retinal cells have been functionally damaged or lost through degeneration. The retina, which consists of neuronal tissue, provides an excellent system to test the therapeutic utility of PSC-based transplantation due to its accessibility and the availability of high-resolution imaging technology to evaluate effects. Preclinical trials in animal models of retinal diseases have shown improvement in visual outcomes following subretinal transplantation of PSC-derived photoreceptors or retinal pigment epithelium (RPE) cells. This review focuses on preclinical studies and clinical trials exploring the use of PSCs for retinal diseases. To date, several phase I/II clinical trials in patients with age-related macular degeneration (AMD) and Stargardt disease (STGD1) have demonstrated the safety and feasibility of PSC-derived RPE transplantation. Additional phase I/II clinical trials using PSC-derived RPE or photoreceptor cells for the treatment of AMD, STGD1, and also retinitis pigmentosa (RP) are currently in the pipeline. As this field continues to evolve, additional technologies may enhance PSC-derived cell transplantation through gene-editing of autologous cells, transplantation of more complex cellular structures such as organoids, and monitoring of transplanted cells through novel imaging technologies.

Association of Acute Macular Neuroretinopathy or Paracentral Acute Middle Maculopathy with Sickle Cell Disease.

PURPOSE: To investigate the structural and microvascular changes in the retina and choriocapillaris in patients with sickle cell disease (SCD) demonstrating acute vision loss and acute macular neuroretinopathy (AMN) or paracentral acute middle maculopathy (PAMM) using multimodal imaging including OCT and OCT angiography (OCTA). DESIGN: Retrospective case series. PARTICIPANTS: Four hemoglobin SS (HbSS) or hemoglobin SC (HbSC) patients who demonstrated vision loss attributed to AMN (n = 2) or PAMM (n = 2). METHODS: Clinical characteristics including best-corrected visual acuity and multimodal imaging features from fundus photography, fluorescein angiography, OCT, and OCTA were analyzed. MAIN OUTCOME MEASURES: Longitudinal changes in the structure and microvasculature of the retina and choriocapillaris were examined. RESULTS: In 2 patients with AMN, characteristic hyperreflective changes were observed in the outer nuclear layer with involvement of the ellipsoid and interdigitation zones. In 1 patient, the lesion was located in the foveal avascular zone, and only flow deficits in the choriocapillaris were noted. In the second patient, no flow loss was observed in the superficial capillary plexus (SCP) corresponding to the lesion, but flow loss was seen in the deep capillary plexus (DCP) and choriocapillaris. At the respective 1-year and 4-month follow-up examinations, the hyperreflectivities improved with no ensuing retinal atrophy. Deep capillary plexus and choriocapillaris flow also improved. Of the 2 patients with PAMM, 1 had PAMM in association with branch retinal arteriolar occlusions. In both patients, a hyperreflective band involving the inner plexiform, inner nuclear, and outer plexiform layers was seen in or adjacent to areas of prior macular thinning. These areas corresponded to flow deficits in both the SCP and DCP. At the respective 1-month and 1-year follow-up examinations, the hyperreflective band improved with ensuing atrophy of the middle retinal layers. OCT angiography demonstrated worsening of flow deficits in the corresponding SCP and DCP. CONCLUSIONS: To the best of our knowledge, this is the first report of AMN and the largest case series of AMN or PAMM in SCD to date. Paracentral acute middle maculopathy may precede macular thinning commonly observed in SCD. OCT angiography is a useful tool to demonstrate associated microvascular changes in AMN and PAMM in SCD.

Mutant Huntingtin Disrupts the Nuclear Pore Complex.

Huntington's disease (HD) is caused by an expanded CAG repeat in the Huntingtin (HTT) gene. The mechanism(s) by which mutant HTT (mHTT) causes disease is unclear. Nucleocytoplasmic transport, the trafficking of macromolecules between the nucleus and cytoplasm, is tightly regulated by nuclear pore complexes (NPCs) made up of nucleoporins (NUPs). Previous studies offered clues that mHTT may disrupt nucleocytoplasmic transport and a mutation of an NUP can cause HD-like pathology. Therefore, we evaluated the NPC and nucleocytoplasmic transport in multiple models of HD, including mouse and fly models, neurons transfected with mHTT, HD iPSC-derived neurons, and human HD brain regions. These studies revealed severe mislocalization and aggregation of NUPs and defective nucleocytoplasmic transport. HD repeat-associated non-ATG (RAN) translation proteins also disrupted nucleocytoplasmic transport. Additionally, overexpression of NUPs and treatment with drugs that prevent aberrant NUP biology also mitigated this transport defect and neurotoxicity, providing future novel therapy targets.