Same-Day Discharge Does Not Increase Resource Utilization Within One Year of Total Joint Arthroplasty.

BACKGROUND: While the safety of rapid recovery total joint arthroplasty is well established, less is known about its impact on postoperative care utilization patterns. We wished to examine whether same-day discharge-and its associated presumed reduction in hospital-based postoperative care and education-translates to the need for more postoperative support during the 1-year recovery period. METHODS: A retrospective review of 1,237 total hip arthroplasty (THA) and 1,710 total knee arthroplasty (TKA) patients who had 0- or 1-day length of stay (LOS) from January 2020 to October 2023 was conducted. The primary outcome was the number of follow-up visits with total joint arthroplasty providers at our institution during the 1-year postoperative period. Secondary outcomes included 30-day emergency department returns, readmissions, 1-year physical therapy utilization, and improvement in Patient-Reported Outcomes Measurement Information System Physical Function scores at 6 to 12 months postoperatively. Bivariate and multivariable analyses were performed to compare outcomes between 0-day and 1-day LOS THA and TKA patients. RESULTS: In both the THA and TKA populations, 0-day LOS patients were younger, had a lower average body mass index, were more likely to be White, men, and had an American Society of Anesthesiologists score < 3 than 1-day LOS patients. After controlling for differences between groups, no significant differences in the number of one-year follow-up visits, physical therapy visits, emergency department returns, or readmissions were seen between 0 and 1-day THA or TKA patients. In TKA patients, 1-day LOS was associated with lower improvements in Patient-Reported Outcomes Measurement Information System Physical Function scores. CONCLUSIONS: After risk adjustment, same-day discharge of THA and TKA patients did not result in increased resource utilization during the one-year postoperative period. In the setting of a coordinated joint arthroplasty program with nurse navigator support, same-day discharge can be safely performed without increasing the need for postoperative care in appropriately selected patients undergoing both THA and TKA.

Soluble CX3CL1 gene therapy improves cone survival and function in mouse models of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a disease that initially presents as night blindness due to genetic deficits in the rod photoreceptors of the retina. Rods then die, causing dysfunction and death of cone photoreceptors, the cell type that mediates high acuity and color vision, ultimately leading to blindness. We investigated immune responses in mouse models of RP and found evidence of microglia activation throughout the period of cone degeneration. Using adeno-associated vectors (AAVs), delivery of genes encoding microglial regulatory signals led to the identification of AAV serotype 8 (AAV8) soluble CX3CL1 (sCX3CL1) as a promising therapy for degenerating cones. Subretinal injection of AAV8-sCX3CL1 significantly prolonged cone survival in three strains of RP mice. Rescue of cones was accompanied by improvements in visual function. AAV8-sCX3CL1 did not affect rod survival, microglia localization, or inflammatory cytokine levels in the retina. Furthermore, although RNA sequencing of microglia demonstrated marked transcriptional changes with AAV8-sCX3CL1, pharmacological depletion of up to ∼99% of microglia failed to abrogate the effect of AAV8-sCX3CL1 on cone survival. These findings indicate that AAV8-sCX3CL1 can rescue cones in multiple mouse models of RP via a pathway that does not require normal numbers of microglia. Gene therapy with sCX3CL1 is a promising mutation-independent approach to preserve vision in RP and potentially other forms of retinal degeneration.

AAV cis-regulatory sequences are correlated with ocular toxicity.

Adeno-associated viral vectors (AAVs) have become popular for gene therapy, given their many advantages, including their reduced inflammatory profile compared with that of other viruses. However, even in areas of immune privilege such as the eye, AAV vectors are capable of eliciting host-cell responses. To investigate the effects of such responses on several ocular cell types, we tested multiple AAV genome structures and capsid types using subretinal injections in mice. Assays of morphology, inflammation, and physiology were performed. Pathological effects on photoreceptors and the retinal pigment epithelium (RPE) were observed. Müller glia and microglia were activated, and the proinflammatory cytokines TNF-α and IL-1ß were up-regulated. There was a strong correlation between cis-regulatory sequences and toxicity. AAVs with any one of three broadly active promoters, or an RPE-specific promoter, were toxic, while AAVs with four different photoreceptor-specific promoters were not toxic at the highest doses tested. There was little correlation between toxicity and transgene, capsid type, preparation method, or cellular contaminants within a preparation. The toxic effect was dose-dependent, with the RPE being more sensitive than photoreceptors. Our results suggest that ocular AAV toxicity is associated with certain AAV cis-regulatory sequences and/or their activity and that retinal damage occurs due to responses by the RPE and/or microglia. By applying multiple, sensitive assays of toxicity, AAV vectors can be designed so that they can be used safely at high dose, potentially providing greater therapeutic efficacy.

Rapid Osteoarthritis and Femoral Head Collapse: A Case Series.

Introduction: Rapidly progressive hip osteoarthritis (OA) leading to femoral head collapse (FHC) following intra-articular (IA) corticosteroid injections is a perplexing variant of OA. We explored eight cases of chronic joint pain treated with IA corticosteroid injections. Subsequently, they experienced swift deterioration of the femoral head integrity within as little as 10 weeks. These cases underscore the need for a comprehensive assessment of risk factors versus benefits in this patient population. Case Report: The study reveals a complex interplay between comorbidities, treatments, and outcomes. Patients exhibited various health factors, including obesity, smoking history, cancer treatment, and deficiencies in Vitamin D levels, which have been found to increase the risk of FHC. Furthermore, the study explores the chondrotoxicity of corticosteroids and local anesthetics used in IA injections. In vitro studies show complete loss of chondrocyte viability after a single dose of corticosteroids, potentially leading to cartilage degradation. In addition, local anesthetics may induce cellular demise and structural alterations in the articular cartilage. These factors highlight various influences affecting treatment outcomes in patients with OA. Conclusion: In conclusion, this case series highlights the rare adverse outcome of rapidly progressive hip OA and FHC following IA corticosteroid injections and possible risk factors. While a definitive etiology remains unclear, the study provides valuable conclusions to aid in future treatment decision-making.

Outcomes in Lumbar Fusion Patients Stratified by the Clinical and Radiographic Degenerative Spondylolisthesis (CARDS) Classification System.

Background and objective The Meyerding classification system remains the most common classification system for spondylolisthesis based on the percentages of vertebral translation. However, the majority of patients with degenerative disease fall into Grade 1, limiting its utility in this subset of patients. The Clinical and Radiographic Degenerative Spondylolisthesis (CARDS) classification system provides a simple radiographic framework for classifying degenerative lumbar spondylolisthesis (DLS) patients by incorporating disc height, kyphosis, and anterior translation. The purpose of this study was to evaluate how clinical characteristics, treatments, and outcomes vary across different CARDS groups in patients undergoing one- or two-level lumbar fusion for DLS. Methods The patients were classified into one of the following four CARDS groups - Type A: advanced disc space collapse with no evidence of kyphosis; Type B: partially preserved disc space with less than 5.0 mm of translation; Type C: partially preserved disc space with greater than 5.0 mm of translation; and Type D: kyphotic alignment. Univariate analyses were performed to compare demographics, symptoms, clinical outcomes, and Patient-Reported Outcomes Measurement Information System (PROMIS) physical (PH) and mental health (MH) scores across groups. Results Ninety-one patients were included in the study. Based on the CARDS classification, there were three (3%) Type A patients, 25 (28%) Type B, 58 (64%) Type C, and five (5%) Type D. No significant differences in baseline demographics, symptom duration, or PROMIS scores were observed across groups. Interbody utilization varied, ranging from 19% in CARDS C (n=11) to 60% in CARDS B (n=15) and D (n=3) patients (p=0.005). Thirty-day clinical outcomes were similar across groups. At an average follow-up of 8.9 months, improvements in PROMIS PH and MH scores and rates of clinically significant improvement were similar across groups. Conclusions Based on our findings, patients undergoing lumbar fusion for DLS present with similar demographic and clinical characteristics and experience similar clinical and patient-reported outcomes when stratified using the CARDS classification system. Posterolateral fusion (PLF) can be effective for various radiographic presentations of DLS. Further research is warranted to assess the utility of CARDS in preoperative planning.

Social Determinants of Health in Maryland Hip Arthroscopy Patients.

Background Prior studies have demonstrated racial and socioeconomic disparities in patient-reported outcome measure (PROM) completion rates, and improvement exists across multiple orthopedic conditions. The purpose of this study was to assess whether these disparities are present in patients undergoing hip arthroscopy (HA) procedures. Methods A retrospective study of 306 patients undergoing HA from 2021 to 2023 was performed. Social determinants of health (SDOH) were compared between HA patients and the general Maryland population. Patients were then classified by whether they completed baseline and six-month PROMs (Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) instrument). Patients who completed PROMIS-PF were classified by whether or not they achieved minimal clinically important difference (MCID) at six months. Demographics and SDOH were compared using univariate analyses between patients who did and did not complete PROMs and between those who did and did not achieve MCID. SDOH were evaluated at the zip-code level using regional health information exchange measures. Results Compared to the Maryland population, HA patients resided in areas of lower social vulnerability. Preoperative and six-month PROMs were completed by 102 (33%) patients. No significant differences in demographics or any SDOH were found between patients who did and did not complete PROMs. Six-month MCID was achieved in 75 of 102 (74%) patients with complete PROMs; no significant differences in demographics or SDOH were observed between patients who did and did not achieve MCID. Conclusions For patients undergoing HA, disparities in patient-reported outcome completion rates and postoperative functional improvement do not appear to be present across demographics and SDOH, indicating equitable care is being delivered.

The Relationship Between Preoperative Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference and Pain Intensity Scores and Early Postoperative Pain and Opioid Consumption After Lumbar Fusion.

Background The Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference and pain intensity measures quantify separate dimensions of pain from the patient's perspective. This study aimed to assess differences in these outcomes and to evaluate whether baseline PROMIS pain scores could be used as a leading indicator of increased pain and opioid consumption during early recovery after lumbar fusion. Methods A retrospective review of 199 consecutive patients undergoing posterolateral fusion (PLF) at a single institution was performed. All patients underwent one to three level lumbar PLF and preoperatively completed the PROMIS pain intensity and PROMIS pain interference measures. Multivariate linear regression was used to assess the relationship between preoperative PROMIS scores and postoperative pain numeric rating scale (NRS) and oral morphine milligram equivalents (OMME) by day after controlling for age, sex, and body mass index (BMI). Results In comparison to patients with the lowest preoperative pain intensity scores, those with the highest scores required significantly more OMME on postoperative day (POD) zero and one (both p<0.05) and had higher pain NRS on POD one (p=0.02). Patients with the highest pain interference scores reported higher pain NRS on POD zero (p=0.02) but required similar OMME at all time points. After controlling for age, sex, and BMI, each one-point increase in preoperative PROMIS pain interference scores was associated with increased OMME on POD zero (ß=0.29, p=0.04) and POD one (ß=0.64, p=0.03). Conclusions Patients with high pain intensity reported higher levels of pain and required more opioids during the first 24 hours postoperatively, while those with high pain interference reported higher levels of pain on the day of surgery but utilized similar amounts of opioids. After risk adjustment, increased baseline PROMIS pain interference scores - but not pain intensity - were associated with increased opioid use. These results suggest that both measures should be considered when identifying patients at risk for increased pain and opioid consumption after PLF.

The association between losartan potassium prescription and postoperative outcomes following total knee arthroplasty: A TriNetX analysis.

BACKGROUND: Total knee arthroplasty (TKA) is a common surgical procedure performed to alleviate pain and improve functional outcomes in patients with knee osteoarthritis and rheumatoid arthritis who have failed conservative treatments. Arthrofibrosis has been extensively studied due to its negative impact on TKA outcomes. Losartan, an angiotensin receptor blocker (ARB), has the potential to improve TKA outcomes by inhibiting TGF-ß and decreasing fibrosis. This study aims to analyze a large-scale, real-world healthcare database to investigate the association between losartan potassium prescription and postoperative outcomes such as readmissions, ED visits, and the need for MUA or revision TKA. HYPOTHESIS: Based on previous literature and the nature of ARBs, it is expected that the addition of losartan will aid in better outcomes for patients following a primary TKA. PATIENTS AND METHODS: In this retrospective observational study, the TriNetX Research Network (TriNetX) database was queried as of June 21, 2023. All patients who underwent a primary total knee arthroplasty (TKA) prior to June 21, 2022 were included. Patients were then divided into two cohorts by whether they had an active losartan potassium prescription within the year prior to their surgery to within 90days postoperatively. Patients were then propensity-matched to eliminate differences in demographics and comorbidities. RESULTS: Losartan TKA patients were 1.18 [OR: 0.85 (95% CI: 0.79-0.90), p<0.001] times less likely to be readmitted within 90days and were 1.15 (OR: 0.87 (95% CI: 0.79-0.96); p=0.009) times less likely to undergo a manipulation under anesthesia (MUA) within the 1-year postoperative period. There were no statistically significant differences in rates of emergency department (ED) visits at 90days postoperatively or revision TKAs at 1year postoperatively. DISCUSSION: In conclusion, patients with an active losartan prescription prior to TKA had a significantly lower likelihood of readmission within 90days and a lower likelihood of undergoing MUA within the 1-year postoperative period compared to patients not taking losartan. This presents an opportunity for further clinical investigation to explore the value of losartan in TKA. LEVEL OF EVIDENCE: III; an observational cohort study.

Disparities in Patient Reported Outcome Measure Completion Rates and Baseline Function in Newly Presenting Spine Patients.

STUDY DESIGN: Retrospective Review. OBJECTIVE: The purpose of this study was to evaluate disparities in patient reported outcome measures (PROM) completion rates and baseline function scores among newly presenting spine patients. SUMMARY OF BACKGROUND DATA: Prior studies have demonstrated that minority patients and those of low socioeconomic status may present with worse physical and mental health on PROMs. As PROMs are increasingly used in clinical care, research, and health policy, accurate assessment of health status among populations relies on the successful completion of PROM instruments. METHODS: A retrospective review of 10,803 consecutive new patients presenting to a single multidisciplinary spine clinic from June 2020 to September 2022 was performed. Univariate statistics were performed to compare demographics between patients who did and did not complete PROMs. Multivariable analysis was used to compare PROM instrument completion rates by race, ethnicity, and Social Vulnerability Index (SVI) and baseline scores among responders. RESULTS: 68.4% of patients completed PROMs at the first clinic visit. After adjusting for age, sex, body mass index, and diagnosis type, patients of non-white race (OR=0.661, 95%-CI=0.599-0.729, P<0.001), Hispanic ethnicity (OR=0.569, 95%-CI=0.448-0.721, P<0.001), and increased social vulnerability (OR=0.608, 95%-CI=0.511-0.723, P<0.001) were less likely to complete PROMs. In the multivariable models, patients of non-white race reported lower levels of physical function (ß=-6.5, 95%-CI=-12.4 to -0.6, P=0.032) and higher levels of pain intensity (ß=0.6, 95%-CI=0.2-1.0, P=0.005). Hispanic ethnicity (ß=1.5, 95%-CI=0.5-2.5, P=0.004) and increased social vulnerability (ß=1.1, 95%-CI=0.4-1.8, P=0.002) were each associated with increased pain intensity. CONCLUSION: Among newly presenting spine patients, those of non-white race, Hispanic ethnicity, and with increased social vulnerability were less likely to complete PROMs. As these subpopulations also reported worse physical function or pain intensity, additional strategies are needed to better capture patient reported health status in order to avoid bias in clinical care, outcomes research and health policy.

Addressing Barriers to Timely Orthopaedic Follow-up for Foot and Ankle Fractures After Emergency Department Visits.

INTRODUCTION: Foot and ankle fractures present common challenges in emergency departments, warranting careful follow-up protocols for optimal patient outcomes. This study investigates the predictors of orthopaedic follow-up for these injuries after an emergency department (ED) visit. METHODS: A retrospective observational study of 1450 patients seen in the ED with foot or ankle fractures from July 2015 to February 2023 was conducted. All included patients were discharged with instructions to follow-up with an orthopaedic provider. Demographic data, fracture details, and follow-up patterns were extracted from medical records. Social vulnerability was assessed using the Centers for Disease Control (CDC) Social Vulnerability Index. Univariate and multivariate analyses were performed to identify predictors of follow-up. A subgroup analysis comparing patients who followed up >7 days from ED presentation (ie, delayed follow-up) to those who followed up within 7 days of presentation was then performed. Statistical significance was assessed at P < .05. RESULTS: Overall, 974/1450 (67.2%) patients followed up with orthopaedics at an average time of 4.16 days. After risk adjustment, Medicaid coverage (odds ratio [OR] = 0.56, P = .018), increased overall social vulnerability (OR = 0.83, P = .032), and increased vulnerability across the dimensions of socioeconomic status (P = .002), household characteristics (P = .034), racial and ethnic minority status (P = .007), and household type and transportation (P = .032) were all associated with lower odds of follow-up. Phalangeal fractures were also associated with decreased odds of follow-up (OR = 0.039, P < .001), whereas ankle fractures were more likely to follow-up (OR = 1.52, P = .002). In the subgroup analysis, patients of older age (P = .008), non-white race (P = .024), motor vehicle accident (MVA) (P = .027) or non-private insurance (P = .027), those experiencing phalangeal fractures (P = .015), and those seen by an orthopaedic provider in the ED (P = .006) were more likely to present with delayed follow-up. CONCLUSION: Patients with increased social vulnerability and Medicaid insurance are less likely to seek follow-up care after presentation to the ED with foot and ankle fractures.

Inpatient or Outpatient: Does Initial Disposition Affect Outcomes in Trimalleolar Ankle Fractures?

Background The repair of trimalleolar fractures can be challenging for surgeons and may be managed as an inpatient or an outpatient. However, it is often unclear whether these patients should be admitted immediately or sent home from the emergency department (ED). This study aims to evaluate trimalleolar fractures treated surgically in the inpatient or outpatient settings to evaluate differences in outcomes for these patients. Methods A retrospective chart review of 223 patients undergoing open reduction internal fixation of a trimalleolar ankle fracture was performed from January 2015 to August 2022. Patients were classified by whether the fixation was performed as an inpatient or outpatient. Outcomes of interest included time from injury to surgery, complications, ED returns, and readmissions within 90 days. Results Inpatients had significantly higher ASA scores, BMI, and rates of comorbidities. Inpatient treatment was associated with faster time to surgery (median 2.0 vs. 9.0 days) and fewer delayed surgeries more than seven days from injury (18.4 vs. 67.9%). There were no differences in complications, 90-day ED returns, readmissions, or reoperation between groups. Conclusions Inpatient admission of patients presenting with trimalleolar ankle fractures resulted in faster time to surgery and fewer surgical delays than outpatient surgery. Despite having more preoperative risk factors, inpatients experienced similar postoperative outcomes as patients discharged home to return for outpatient surgery. Less restrictive admission criteria may improve the patient experience by providing more patients with support and pain control in the hospital setting while decreasing the time to surgery.

Optimizing Patient Outcomes in Spinal Surgery: An Investigation Into Anesthesiologists' Case Volume.

Introduction Nearly one million patients in the United States undergo spine surgical procedures annually to seek relief from chronic back and neck pain. A multidisciplinary approach is key to ensuring the efficiency and safety of the surgical process, with the anesthesia team, nursing, surgeon, and healthcare facilities all playing a role. The purpose of this study is to capture potential associations between the anesthesiologists' case volume and patient postoperative outcomes in the early recovery period. Methods A retrospective review of anterior cervical discectomy and fusion (ACDF), lumbar decompression (LD), and lumbar fusion (LF) patients from July 2019 to June 2023 was performed. Anesthesiologists were categorized into low, medium, and high volumes of spine surgical cases. Univariate analysis was performed on patient demographics, intraoperative measures, post-anesthesia care unit (PACU) measures, and postoperative measures by anesthesiologist volume. Results This study included 545 ACDF, 815 LD, and 1,144 LF patients. There were no differences between groups in ACDF patients by anesthesiologist volume. When examining patients undergoing LD, there was a difference in patients with an American Society of Anesthesiologists (ASA) physical status classification of three or greater (low volume: 41.7% vs. medium volume: 53.7% vs. high volume: 45.0%; p=0.029). When examining patients undergoing LF, there were differences in patients with low temperatures in PACU (low volume: 2.8% vs. medium volume: 7.3% vs. high volume: 4.2%; p=0.044) and the percentage of patients with a 90-day emergency department return (low volume: 7.7% vs. medium volume: 11.9% vs. high volume: 7.0%; p=0.024). Conclusion While this study found a minimal impact of anesthesiologist volume on postoperative outcomes, recent literature has emphasized the critical role of teamwork and specialized surgical teams to enhance efficiency and patient care. Further studies are warranted to identify other variables in anesthesia, nursing, and surgical team workflow that may impact postoperative outcomes in spinal surgeries.

AAV-Txnip prolongs cone survival and vision in mouse models of retinitis pigmentosa.

Retinitis pigmentosa (RP) is an inherited retinal disease affecting >20 million people worldwide. Loss of daylight vision typically occurs due to the dysfunction/loss of cone photoreceptors, the cell type that initiates our color and high-acuity vision. Currently, there is no effective treatment for RP, other than gene therapy for a limited number of specific disease genes. To develop a disease gene-agnostic therapy, we screened 20 genes for their ability to prolong cone photoreceptor survival in vivo. Here, we report an adeno-associated virus vector expressing Txnip, which prolongs the survival of cone photoreceptors and improves visual acuity in RP mouse models. A Txnip allele, C247S, which blocks the association of Txnip with thioredoxin, provides an even greater benefit. Additionally, the rescue effect of Txnip depends on lactate dehydrogenase b (Ldhb) and correlates with the presence of healthier mitochondria, suggesting that Txnip saves RP cones by enhancing their lactate catabolism.

Retinitis pigmentosa is an inherited eye disease affecting around one in every 4,000 people. It results from genetic defects in light sensitive cells of the retina, called photoreceptor cells, which line the back of the eye. Though vision loss can occur from birth, retinitis pigmentosa usually involves a gradual loss of vision, sometimes leading to blindness. Rod photoreceptors, which are responsible for vision in low light, are impacted first. The disease then affects cone photoreceptors, the cells that detect light during the day, providing both color and sharp vision. Around 100 mutated genes associated with retinitis pigmentosa have been identified, but only a handful of families with one of these mutant genes have been treated with a gene therapy specific for their mutated gene. There are currently no therapies available to treat the vast number of people with this disease. The mutations that cause retinitis pigmentosa directly affect the rod cells that detect dim light, leading to loss of night vision. There is also an indirect effect that causes cone photoreceptors to stop working and die. One theory to explain this two-step disease process relates to the fact that cone photoreceptors are very active cells, requiring a high level of energy, nutrients and oxygen. If surrounding rod cells die, cone photoreceptors may be deprived of some essential supplies, leading to cone cell death and daylight vision loss. To examine this theory, Xue et al. tested a new gene therapy designed to alleviate the potential shortfall in nutrients. The experiments used three different strains of mice that had the same genetic mutations as humans with retinitis pigmentosa. The gene therapy used a virus, called adeno-associated virus (AAV), to deliver 20 different genes to cone cells. Each of the 20 genes tested plays a different role in cells' processing of nutrients to provide energy. After administering the treatment, Xue et al. monitored the mice to see whether or not their vision was affected, and how cone cells responded. Only one of the 20 genes, Txnip, delivered using gene therapy, had a beneficial effect, prolonging cone cell survival in all three mouse strains. The mice that received Txnip also retained their ability to discern moving stripes on vision tests. Further investigations demonstrated that activating Txnip forced the cones to start using a molecule called lactate as an energy source, which could be more available to them than glucose, their usual fuel. These cells also had healthier mitochondria ­ the compartments inside cells that produce and manage energy supplies. This dual effect on fuel use and mitochondrial health is thought to be the basis for the extended cone survival and function. These experiments by Xue et al. have identified a good gene therapy candidate for treating retinitis pigmentosa independently of which genes are causing the disease. Further research will be required to test the safety of the gene therapy, and whether its beneficial effects translate to humans with retinitis pigmentosa, and potentially other diseases with unhealthy photoreceptors.

Nrf2 overexpression rescues the RPE in mouse models of retinitis pigmentosa.

Nrf2, a transcription factor that regulates the response to oxidative stress, has been shown to rescue cone photoreceptors and slow vision loss in mouse models of retinal degeneration (rd). The retinal pigment epithelium (RPE) is damaged in these models, but whether it also could be rescued by Nrf2 has not been previously examined. We used an adeno-associated virus (AAV) with an RPE-specific (Best1) promoter to overexpress Nrf2 in the RPE of rd mice. Control rd mice showed disruption of the regular array of the RPE, as well as loss of RPE cells. Cones were lost in circumscribed regions within the cone photoreceptor layer. Overexpression of Nrf2 specifically in the RPE was sufficient to rescue the RPE, as well as the disruptions in the cone photoreceptor layer. Electron microscopy showed compromised apical microvilli in control rd mice but showed preserved microvilli in Best1-Nrf2-treated mice. The rd mice treated with Best1-Nrf2 had slightly better visual acuity. Transcriptome profiling showed that Nrf2 upregulates multiple oxidative defense pathways, reversing declines seen in the glutathione pathway in control rd mice. In summary, Nrf2 overexpression in the RPE preserves RPE morphology and survival in rd mice, and it is a potential therapeutic for diseases involving RPE degeneration, including age-related macular degeneration (AMD).