The mouse retinal pigment epithelium mounts an innate immune defense response following retinal detachment.

The retinal pigment epithelium (RPE) maintains photoreceptor viability and function, completes the visual cycle, and forms the outer blood-retinal barrier (oBRB). Loss of RPE function gives rise to several monogenic retinal dystrophies and contributes to age-related macular degeneration. Retinal detachment (RD) causes separation of the neurosensory retina from the underlying RPE, disrupting the functional and metabolic relationships between these layers. Although the retinal response to RD is highly studied, little is known about how the RPE responds to loss of this interaction. RNA sequencing (RNA-Seq) was used to compare normal and detached RPE in the C57BL6/J mouse. The naïve mouse RPE transcriptome was compared to previously published RPE signature gene lists and from the union of these 14 genes (Bmp4, Crim1, Degs1, Gja1, Itgav, Mfap3l, Pdpn, Ptgds, Rbp1, Rnf13, Rpe65, Slc4a2, Sulf1 and Ttr) representing a core signature gene set applicable across rodent and human RPE was derived. Gene ontology enrichment analysis (GOEA) of the mouse RPE transcriptome identified expected RPE features and functions, such as pigmentation, phagocytosis, lysosomal and proteasomal degradation of proteins, and barrier function. Differentially expressed genes (DEG) at 1 and 7 days post retinal detachment (dprd) were defined as mRNA with a significant (padj≤0.05) fold change (FC) of 0.67 ≥ FC ≥ 1.5 in detached versus naïve RPE. The RPE transcriptome exhibited dramatic changes at 1 dprd, with 2297 DEG identified. The KEGG pathways and biological process GO groups related to innate immune responses were significantly enriched. Lipocalin 2 (Lcn2) and several chemokines were upregulated, while numerous genes related to RPE functions, such as pigment synthesis, visual cycle, phagocytosis, and tight junctions were downregulated at 1 dprd. The response was largely transient, with only 18 significant DEG identified at 7 dprd, including upregulation of complement gene C4b. Validation studies confirmed RNA-Seq results. Thus, the RPE quickly downregulates cell-specific functions and mounts an innate immune defense response following RD. Our data demonstrate that the RPE contributes to the inflammatory response to RD and may play a role in attraction of immune cells to the subretinal space.

NO EFFECT OF REAL-WORLD UNIVERSAL FACE MASKING ON POST-INTRAVITREAL INJECTION ENDOPHTHALMITIS RATE AT A SINGLE TERTIARY ACADEMIC CENTER.

PURPOSE: To determine whether universal masking during COVID-19 altered rate and outcomes of postinjection endophthalmitis. METHODS: Retrospective, single-site, comparative, cohort study. Eyes diagnosed with endophthalmitis within 4 weeks of intravitreal injection at the University of Michigan from August 1, 2012, to November 15, 2022, were identified. Cases were considered "masking" between March 15, 2020, and November 15, 2022. Endophthalmitis rate, visual acuity, and microbial spectrum were investigated. RESULTS: There were 20 postinjection endophthalmitis cases out of 72,194 injections (0.028%; one in 3,571 injections) premasking and 10 of 38,962 with universal masking (0.026%; one in 3,846 injections; odds ratio 0.9; 95% [confidence interval]: 0.4-2.0). Referral from the community was unchanged with 32 cases referred premasking (0.35 cases/month) and 10 cases with masking (0.31 cases/month). Presenting mean the logarithm of the minimum angle of resolution visual acuity with masking of all postinjection endophthalmitis cases trended worse (2.35 ± 0.40) compared with premasking (2.09 ± 0.48; P = 0.05) with light perception visual acuity more common with masking (31.6% vs. 10.9%, P = 0.06). There was no delay in time from procedure to initial treatment ( P = 0.36), no difference in the rate of initial treatment with tap and inject (T/I), and similar positive-culture rates ( P = 0.77) between the cohorts. Visual acuity after 30 days of follow-up was clinically unchanged (∼20/500 vs. 20/400; P = 0.59). CONCLUSION: Universal masking had no effect on postinjection endophthalmitis rate or on the rate of culture-positive cases. Although presenting visual acuity appeared worse with masking, this was not statistically significant, and current treatment paradigms resulted in similar visual outcomes.

Retinal Detachments after Open-Globe Injury: Risk Factors and Outcomes.

PURPOSE: To identify risk factors for retinal detachment (RD) after open-globe injury (OGI) and evaluate outcomes of RD repair after OGI. DESIGN: Case-control study. PARTICIPANTS: Overall, 769 patients presented with 786 OGIs, which were surgically managed with ≥ 30 days of follow-up. Of the 786 eyes, 223 developed RD, the other 551 served as controls, and RD status of 12 eyes was unknown. METHODS: A retrospective chart review was performed of all OGIs presented to the University of Michigan between 2000 and 2022. Multivariable regression identified risk factors for RD after OGI and predictors of poor vision after RD repair. Kaplan-Meier analysis estimated time from OGI to RD. MAIN OUTCOME MEASURE: Predictors of visual outcome after RD repair after OGI. RESULTS: After OGI, 223 (28.4%) of 786 eyes were diagnosed with RD, with > 73% diagnosed within a month. Predictors of RD include posterior injury (zone II vs. I odds ratio [OR], 1.60 [95% confidence interval {CI}, 1.04-2.46]; P = 0.0331; zone III vs. I OR, 2.29 [1.53-3.41]; P < 0.0001), vitreous hemorrhage (OR, 2.29 [1.54-3.1]; P < 0.0001), and presenting acuity worse than count fingers (CFs) (OR, 2.65 [1.69 - 4.16]; P < 0.0001). Retinal detachment repair took place in 142 of 223 eyes. The mean logarithm of minimal angle of resolution visual acuity (VA) improved from 2.3 ± 0.8 to 1.7 ± 0.9 after RD repair at 6-month follow-up, with 51.2% of eyes achieving CF or better vision. Single surgery anatomic success rate was 69.7% and final anatomic success was 88%. Predictors of vision worse than CF include history of ocular surgery (OR, 0.32 [0.11-0.94]; P = 0.039), proliferative vitreoretinopathy (PVR; OR, 0.39 [0.16 - 0.92]; P = 0.032), aphakia (OR, 0.25 [0.08 - 0.77]; P = 0.016), and redetachment (OR, 0.26 [0.1 - 0.63]; P = 0.003). CONCLUSIONS: Most RD occur within the first month after OGI. Patients with posterior injuries, vitreous hemorrhage, or poor presenting VA were more likely to develop RD after OGI. Anatomic success was achieved in the majority, as was final VA of CF vision or better. History of ocular surgery, PVR at time of repair, aphakia, and redetachment were risk factors for a poor outcome. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

An Evaluation of the Repeatability of Visual Function Following Surgical Repair of Macula-Off Rhegmatogenous Retinal Detachment.

Purpose: To evaluate the reliability and reproducibility of visual function assessments for patients with macula-off rhegmatogenous retinal detachment (RRD). Methods: This prospective study included patients with unilateral macula-off RRD of <10-day duration successfully treated with a single, uncomplicated surgery at least 1 year following repair. Visual function assessments were performed at time of enrollment and 1 month later. Testing included Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), low-contrast visual acuity (VA) 2.5% and 5%, contrast sensitivity assessment with Mars and Gabor patches, reading speed (acuity, speed, and critical print size), color vision testing (protan, deutan, and tritan), and microperimetry. Spectral-domain ocular coherence tomography (SD-OCT) was performed. Paired t-statistics were used to compare values between visits and between the study and fellow eyes. Results: Fourteen patients (9 male, 5 female) with a mean age of 69 years at time of surgery were evaluated. Correlation coefficients across the two visits were highest for ETDRS BCVA (0.97), tritan color vision testing (0.96), and low-contrast VA 5% (0.96), while the average t-statistic was largest for low-luminance deficit (4.2), ETDRS BCVA (4.1), and reading speed critical print size (3.7). ETDRS BCVA did not correlate with SD-OCT findings. Conclusions: ETDRS BCVA can be considered a highly reliable and reproducible outcome measure. LLVA, protan color discrimination, contrast sensitivity, and reading speed may be useful secondary outcome measures. Translational Relevance: This study provides guidance on the selection of visual function outcome measures for clinical trials of patients with macula-off RRD.

Increase in Retinal Detachment Repair Over a Ten-Year Period at an Academic Center Compared to National Trends.

BACKGROUND AND OBJECTIVE: This study aimed to determine whether cases of surgical retinal detachment (RD) repair at a tertiary care center from January 1, 2011 to December 31, 2020 increased proportionately to macular surgery cases as a control and to national trends. PATIENTS AND METHODS: Current Procedural Terminology codes were used to identify cases of primary RD repair (67107, 67108), complex RD repair (67113), pneumatic retinopexy (67110), and vitrectomy with membrane peeling (67041, 67042) at an academic center and in the Part B National Summary Data Files. Numbers of cases and mean case times at the academic center were determined. RESULTS: We identified 5,183 and 948,831 operative cases locally and nationally, respectively. Between 2011 and 2019, the total volume of RD repair at the academic center increased by 118.7%, compared to 23.3% for cases of membrane peeling. In contrast, surgical RD repairs and membrane peelings increased by 26.0% and 6.8% cases nationally. The ratio of RD repairs to membrane peelings from 2011 to 2019 increased from 1.5 to 2.6 locally compared to 0.6 to 0.7 nationally. Complex RD repairs increased more than primary RD repairs locally (129.3% vs 110.9% cases) and less than primary RD repairs nationally (20.6% versus 30.2% cases). CONCLUSION: Cases of surgical RD repair increased disproportionately compared to macular surgery at our institution and compared to RD repairs nationwide. [Ophthalmic Surg Lasers Imaging Retina 2023;54:505-511.].

Clinical Characteristics and Visual Outcomes of Acute Syphilitic Posterior Placoid Chorioretinopathy.

PURPOSE: To evaluate presenting features and visual outcomes in eyes with acute syphilitic posterior placoid chorioretinopathy (ASPPC). DESIGN: Retrospective cohort study. SUBJECTS: A total of 24 eyes of 17 adult patients with ASPPC. METHODS: Chart review of patients with ASPPC who presented to the University of Michigan W. K. Kellogg Eye Center between January 1, 2012, and November 4, 2022. Demographic and clinical information, fundus photographs, fundus autofluorescence, and spectral-domain-OCT (SD-OCT) findings were reviewed. MAIN OUTCOME MEASURES: Clinical characteristics and visual acuity (VA) on presentation and follow-up examination. RESULTS: The median age was 46 (interquartile range [IQR], 38-51) years. At presentation, 20 (83.3%) eyes had subjectively decreased vision, with a median initial VA of 0.54 (IQR, 0.35-1.00) logarithm of the minimum angle of resolution (logMAR); at 45 days, median logMAR VA was 0.096 (IQR, 0.02-0.17). Initial VA was positively associated with posterior pole-sparing lesions (coefficient estimate [CE], -0.75; 95% confidence interval [CI], -1.38 to -0.12); P = 0.03), and negatively associated with ellipsoid zone (EZ) disruption (CE, 0.72; 95% CI, 0.03-1.42; P = 0.04), subfoveal EZ disruption (CE, 0.62; 95% CI, 0.02-1.23; P = 0.046), and initial hyperreflective foci on SD-OCT (CE, 0.66; 95% CI, 0.09-1.23; P = 0.03). Female eyes were more likely (hazard ratio [HR], 3.36; 95% CI, 1.07-10.6; P = 0.04), and eyes with optic nerve abnormality were less likely (HR, 0.34; 95% CI, 0.12-0.96; P = 0.04), to achieve a VA ≥ 20/40 (logMAR, 0.30). CONCLUSIONS: This study of patients with ASPPC showed that symptomatic eyes had an improvement from a median VA of 20/69 on presentation to a median VA of 20/25 at 45 days. Female sex and absence of optic nerve involvement were associated with higher probability of achieving ≥ 20/40. These findings provide refined guidance for counseling patients who present with decreased vision due to ASPPC. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

AUTOPHAGY IN THE EYE: FROM PHYSIOLOGY TO PATHOPHYSOLOGY.

Autophagy is a catabolic self-degradative pathway that promotes the degradation and recycling of intracellular material through the lysosomal compartment. Although first believed to function in conditions of nutritional stress, autophagy is emerging as a critical cellular pathway, involved in a variety of physiological and pathophysiological processes. Autophagy dysregulation is associated with an increasing number of diseases, including ocular diseases. On one hand, mutations in autophagy-related genes have been linked to cataracts, glaucoma, and corneal dystrophy; on the other hand, alterations in autophagy and lysosomal pathways are a common finding in essentially all diseases of the eye. Moreover, LC3-associated phagocytosis, a form of non-canonical autophagy, is critical in promoting visual cycle function. This review collects the latest understanding of autophagy in the context of the eye. We will review and discuss the respective roles of autophagy in the physiology and/or pathophysiology of each of the ocular tissues, its diurnal/circadian variation, as well as its involvement in diseases of the eye.

Quantitative contrast sensitivity test to assess visual function in central serous chorioretinopathy.

BACKGROUND: To characterise the contrast sensitivity function (CSF) in central serous chorioretinopathy (CSCR) compared with healthy controls using novel computerised contrast sensitivity (CS) testing with active learning algorithms. METHODS: Prospective observational study measuring CSF in CSCR eyes and controls using the Manifold Platform (Adaptive Sensory Technology, San Diego, California). Mixed effects multivariate regression models were used. Outcomes included area under the log CSF (AULCSF), CS thresholds at 1, 1.5, 3, 12 and 18 cycles per degree (cpd) and best-corrected visual acuity (BCVA). Associations of contrast outcomes with structural findings on optical coherence tomography (OCT) and subjective symptomatology were investigated. RESULTS: Forty CSCR eyes and 89 controls were included with median BCVA logarithm of median angle of resolution 0.10 (20/25) versus 0.00 (20/20), respectively (p=0.01). When accounting for age, CSCR was associated with significantly reduced median AULCSF (p=0.02, ß=-0.14) and reduced CS thresholds at 6 cpd (p=0.009, ß=-0.18), 12 cpd (p<0.001, ß=-0.23) and 18 cpd (p=0.04, ß=-0.09), versus controls. Within the CSCR group, subjectively perceived visual impairment (N=22) was associated with significantly decreased CS thresholds at all spatial frequencies and in AULCSF compared with asymptomatic CSCR eyes (N=18). Ellipsoid zone attenuation and subfoveal fluid on OCT were associated with decreased AULCSF and CS thresholds specifically at 3, 6 and 12 cpd, whereas presence of extrafoveal fluid at 1.5 and 3 cpd. CONCLUSION: Contrast sensitivity is significantly reduced in CSCR, and strongly correlates with subjective visual impairment. Different structural biomarkers correlate with contrast thresholds reductions at different spatial frequencies.

Risk Factors for Enucleation Following Open Globe Injury: A 17-Year Experience.

Purpose: At the time of open globe injury (OGI), it may be difficult for clinicians to predict which eyes are at highest risk for requiring enucleation. We performed a 17-year retrospective cohort study to report outcomes and risk factors for enucleation following open globe injuryto better aid clinicians counseling patients at OGI diagnosis. Methods: A retrospective cohort study of all patients who presented to the University of Michigan with open globe injury (OGI) and were surgically managed between January 2000 and July 2017 was conducted. At least 30 days of follow-up was required. All eyes that ultimately underwent enucleation following OGI were identified and their clinical course analyzed. The main outcome measured was the rate of enucleation after OGI. Results: There were 587 eyes meeting inclusion criteria. The mean patient age was 40.75 ± 25.1 (range 1-91). 441/585 (75.4%) patients were male. Average follow-up time was 1029.9 ± 1285.9 days. 116/587 eyes (19.8%) required enucleation after OGI, with 81.9% undergoing enucleation less than 30 days from injury. In enucleated eyes, the mean presenting logMAR vision was 2.91 ± 0.47 (Snellen equivalent between hand motion and light perception). The most common mechanism of injury requiring enucleation was globe rupture, 89/116 (76.7%), with 14/116 (12.1%) penetrating injuries and 13/116 (11.2%) perforating injuries. The mean age of patients that underwent enucleation was 45.6 ± 22.5 (range 3-91). Conclusion: Open globe injuries are often visually devastating and a significant number of cases ultimately require enucleation. Despite emergent closure within 24 hours, 19.8% of eyes managed for OGI at our institution required eventual enucleation. 81.2% of these eyes required enucleation within 30 days of injury. Wound length greater than 10 mm, uveal prolapse, higher zone of injury, IOFB, and RAPD were identified as risk factors that predict future need for enucleation.

Hypoxia-Inducible Factor-1α in Rods Is Neuroprotective Following Retinal Detachment.

Purpose: Following retinal detachment (RD) photoreceptors (PRs) sustain hypoxic stress and eventually die. Hypoxia-inducible factor-1α (HIF-1α) plays a central role in cellular adaptation to hypoxia. The purpose of this study is to determine the necessity of HIF-1α on PR cell survival after RD. Methods: Experimental RD was created in mice by injection of hyaluronic acid (1%) into the subretinal space. Mice with conditional HIF-1α knockout in rods (denoted as HIF-1αΔrod) were used. HIF-1α expression in retinas was measured real-time polymerase chain reaction (RT-PCR) and Western blotting. PR cell death after RD was evaluated using TUNEL assay. Optical coherence tomography (OCT) and histology were used to evaluate retinal layer thicknesses and PR cell densities. A hypoxia signaling pathway PCR array was used to examine the expression of HIF-1α target genes after RD. Results: HIF-1α protein levels were significantly increased after RD, and depletion of HIF-1α in rods blunted this increase. A compensatory increase of HIF-2α protein was observed in HIF-1αΔrod mice. Conditional knockout (cKO) of HIF-1α in rods did not lead to any morphologic change in attached retinas but resulted in significantly increased PR cell loss after RD. HIF-1α cKO in rods altered the responses to retinal detachment for 25 out of 83 HIF-1α target genes that were highly enriched for genes involved in glycolysis. Conclusions: Rod-derived HIF-1α plays a key role in the PR response to RD, mediating the transcriptional activity of a battery of genes to promote PR cell survival.

Loss of Fas Receptor Function Preserves Photoreceptor Structure and Function in Two Mouse Models of Inherited Retinal Degeneration.

Purpose: The genetic heterogeneity of inherited retinal degeneration (IRD) has limited the development of mutation-specific therapies, necessitating the development of therapeutic approaches targeting broadly shared pathophysiologic pathways. The Fas receptor has been reported as a contributor to retinal cell death and inflammation in a wide variety of ocular diseases. The purpose of this study was to assess targeting the Fas pathway as a novel mutation-independent approach to improve photoreceptor survival in IRD. Methods: We examined the effects of genetic inactivation of the Fas receptor on retinal degeneration in two distinct IRD mouse models, P23H and rd10. The Fas-lpr mouse, which contains a functionally inactive Fas receptor, was crossed with the P23H and rd10 mice to generate P23H/Fas-lpr and rd10/Fas-lpr mice. Fas activation, photoreceptor survival and retinal function were assessed. Results: We detected elevated levels of Fas receptor and microglial activation in the retinas of both P23H and rd10 mice. Inactivation of Fas in these two IRD models (P23H/Fas-lpr and rd10/Fas-lpr mice) resulted in reduced cell death, increased photoreceptor survival, improved retinal function, and reduced microglial activation and inflammatory cytokine production. Conclusions: The protective effect of a nonfunctional Fas receptor in two different mouse models of retinal degeneration suggests that whereas the individual IRD mutation may be specific, the retina's response to the different stressors appears to be shared and driven by Fas. Reducing Fas activity might represent a potential mutation-independent therapeutic approach to preserve retinal structure and function in patients with IRD.

Endophthalmitis, Visual Outcomes, and Management Strategies in Eyes with Intraocular Foreign Bodies.

Purpose: Ocular trauma with intraocular foreign body (IOFB) can have devastating visual consequences. Management and antimicrobial strategies remain variable due to the infrequency and heterogeneity of presentation. Our goal was to identify risk factors for endophthalmitis and poor visual outcomes in cases of IOFB and investigate management strategies. Patients and Methods: A retrospective chart review was conducted in 88 eyes of 88 patients suffering traumatic injury with IOFB at the University of Michigan between January 2000 and December 2019. Medical records were reviewed to characterize the injuries and IOFBs as well as how clinical presentation and treatment modalities were associated with outcomes. Results: Delayed presentation (P=0.016) and organic IOFB (P=0.044) were associated with development of endophthalmitis. Retinal detachment (P=0.012), wound length greater than 5 mm (P=0.041), and poor presenting visual acuity (P=0.003) correlated with poor final visual outcome. Antibiotic prophylaxis was given to all patients, though agents and routes of delivery varied. Endophthalmitis developed in 4.9% of the eyes after initial management, with primary and secondary removal of posterior segment IOFBs associated with similar rates of endophthalmitis (P=1.000). Conclusion: Poor presenting visual acuity and severity of injury, as measured by large wound and retinal detachment, correlate with poor visual outcome. Prompt globe closure and antimicrobial prophylaxis are critical for infection prevention. In cases where IOFB removal and globe closure cannot be performed concurrently, primary globe closure with aggressive antibiotic prophylaxis offers a reasonable alternative to prevent endophthalmitis.

Cell Death in AMD: The Rationale for Targeting Fas.

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the developed world. While great advances have been made in the treatment of the neovascular ("wet") form of the disease, there is still a significant need for therapies that prevent the vision loss associated with the advanced forms of dry, atrophic AMD. In this atrophic form, retinal pigment epithelial (RPE) and photoreceptor cell death is the ultimate cause of vision loss. In this review, we summarize the cell death pathways and their relation to RPE and retinal cell death in AMD. We review the data that support targeting programmed cell death through inhibition of the Fas receptor as a novel approach to preserve these structures and that this effect results from inhibiting both canonical death pathway activation and reducing the associated inflammatory response. These data lay the groundwork for current clinical strategies targeting the Fas pathway in this devastating disease.

Expanded Clinical Spectrum of Pentosan Polysulfate Maculopathy: A Macula Society Collaborative Study.

PURPOSE: Explore the spectrum of clinical manifestations of pentosan polysulfate sodium (PPS) maculopathy observed across a range of practice settings. DESIGN: Multi-institutional retrospective study. PARTICIPANTS: Patients exhibiting findings suggestive of PPS maculopathy identified from April 30, 2019, to December 4, 2020. METHODS: Members of the Macula Society submitted cases of presumed PPS maculopathy for consideration in this series. Diagnosis was confirmed by masked review of fundus imaging. Clinical characteristics of confirmed cases were summarized with descriptive statistics. MAIN OUTCOME MEASURES: Pentosan polysulfate exposure characteristics and fundus imaging features. RESULTS: There were 74 patients with PPS maculopathy included in the current study. Median (interquartile range) age at diagnosis was 62.0 years (56.0-65.8). The median duration of exposure to PPS was 14.0 years (10.2-18.9), with a median cumulative exposure of 1.5 kg (0.9-2.4). The most common presenting symptom was decreased or blurry vision (66.2%), followed by prolonged dark adaption or nyctalopia (32.4%). The most common referral diagnosis was age-related macular degeneration (54.1%); 16.2% of patients were referred for suspected PPS maculopathy. Novel imaging findings emerged, including highly asymmetric disease in 2 patients and a prominent vitelliform maculopathy in 2 patients. CONCLUSIONS: Most patients with PPS maculopathy exhibit characteristic findings on multimodal fundus imaging in the setting of high cumulative exposure to the oral drug. Some patients in the current study manifested novel imaging findings, expanding our understanding of the phenotypic spectrum of this condition. We recommend considering standardized ophthalmic screening of patients treated with PPS.

Outcomes of Penetrating Keratoplasty After Open Globe Injury.

PURPOSE: The purpose of this study was to investigate the clinical features, surgical outcomes, and prognostic factors of penetrating keratoplasty (PKP) after open globe injury (OGI). METHODS: A retrospective review of all patients treated for OGI between January 2000 and July 2017 was conducted. Demographic, preoperative, perioperative, and postoperative data were collected for those who underwent PKP after OGI. The predictive value of each preoperative variable on graft failure was assessed using univariate and multivariable Cox proportional hazards models, and the predictive value of variables on post-PKP visual outcome was assessed using both univariate and multivariable logistic regression models. All eyes that underwent PKP after OGI were included unless they had less than 365 days of follow-up. RESULTS: Forty-six eyes that underwent PKP met inclusion criteria. The median age was 46 years (interquartile range = 23.00-61.25), median follow-up was 78.5 months (interquartile range = 38.63-122.02), and 37 of 46 subjects (80.4%) were male. The observed 1- and 5-year graft survival estimates were 80.4% and 41.7%, respectively. Factors statistically associated with graft failure in multivariable analyses were rejection episode, hazard ratio (HR) = 3.29; retinal detachment (RD), HR = 3.47; and endophthalmitis, HR = 6.27. Fifteen of 42 eyes (35.7%) regained ambulatory vision (20/200 or better). The strongest predictors of vision worse than 20/200 at the last follow-up were RD, odds ratio (OR) = 43.88; graft rejection, OR = 12.42; and injury outside the workplace, OR = 25.05. CONCLUSIONS: Despite a high graft survival at 1 year, most of the patients did not regain ambulatory vision. Graft rejection, RD, and endophthalmitis were risk factors for graft failure. These factors should be considered when counseling patients regarding PKP after OGI.

Clinical Presentation and Outcomes of Rhegmatogenous Retinal Detachments During the COVID-19 Lockdown and Its Aftermath at a Tertiary Care Center in Michigan.

BACKGROUND AND OBJECTIVE: To investigate the effect of the coronavirus disease 2019 (COVID-19) lockdown on the presentation and management of acute, primary rhegmatogenous retinal detachment (RRD). PATIENTS AND METHODS: This was a single-center, consecutive case series with historic controls, examining patients during the COVID-19 "stay-at-home" order (March 24 to June 1, 2020), the subsequent reopening phase (June 1 to July 31, 2020), and corresponding preceding intervals (March 24 to July 31, 2016 to 2019). RESULTS: Despite a significant increase in patients presenting with macula-off RRD during the COVID-19 lockdown compared to the 2016 to 2019 timeframe (P = .03), the rate of single surgery anatomical success was similar between all groups (P = .66), as was final visual acuity (P = .61). No delays between presentation and surgical intervention were observed during the lockdown (P = .49). CONCLUSIONS: Despite the limitations of the COVID-19 lockdown, patients underwent surgery in a timely manner and achieved comparable visual outcomes to controls before COVID-19. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:593-600.].

Active Learning of Contrast Sensitivity to Assess Visual Function in Macula-off Retinal Detachment.

PURPOSE: To characterize the contrast sensitivity function (CSF) in patients with successful repair of macula-off rhegmatogenous retinal detachment (RD) using an adaptive computerized contrast testing device. METHODS: CSF was prospectively measured in macula-off RD patients following successful repair and age-matched controls at W. K. Kellogg Eye Center and Massachusetts Eye and Ear, employing the active learning device Manifold Contrast Vision Meter (Adaptive Sensory Technology, San Diego, CA). Outcome measures included average area under the CSF curve (AULCSF), CS thresholds at 1-18 cycles per degree (cpd) and best correctd visual acuity (BCVA) in RD eyes fellow eyes and controls. A sub-analysis was performed in eyes with BCVA of 20/30 or better. RESULTS: Twenty-three macula-off RD eyes status post repair, fellow healthy eyes and 45 age-matched control eyes underwent CSF testing. The mean BCVA of the 23 RD eyes was 0.250 logMAR, significantly reduced compared to fellow eyes 0.032 (p<0.001) and controls 0.026 (p< 0.00001). There was a statistically significant reduction in AULCSF in RD eyes compared to the fellow eyes (p<0.0001) and to age-matched controls (Z-score -0.90, p<0.0001) and CSF reduction across all spatial frequencies. In the 15 RD eyes with BCVA of 20/30 or better, the mean CSF was significantly reduced compared to fellow eyes (p=0.0158) and controls (p=0.0453). CONCLUSIONS: CSF in macula-off RD eyes following repair was significantly reduced compared to fellow eyes and age-matched controls. CSF seems to be a promising visual function endpoint with potential applications in the clinical practice and future clinical trials.

Conditional Knock out of High-Mobility Group Box 1 (HMGB1) in Rods Reduces Autophagy Activation after Retinal Detachment.

After retinal detachment (RD), the induction of autophagy protects photoreceptors (PR) from apoptotic cell death. The cytoplasmic high-mobility group box 1 (HMGB1) promotes autophagy. We previously demonstrated that the deletion of HMGB1 from rod PRs results in a more rapid death of these cells after RD. In this work, we tested the hypothesis that the lack of HMGB1 accelerates PR death after RD due to the reduced activation of protective autophagy in the retina after RD. The injection of 1% hyaluronic acid into the subretinal space was used to create acute RD in mice with a rhodopsin-Cre-mediated conditional knockout (cKO) of HMGB1 in rods (HMGB1Δrod) and littermate controls. RD sharply increased the number of apoptotic cells in the outer nuclear layer (ONL), and this number was further increased in HMGB1Δrod mouse retinas. The activation of autophagy after RD was reduced in the HMGB1Δrod mouse retinas compared to controls, as evidenced by diminished levels of autophagy regulatory proteins LC3-II, Beclin1, ATG5/12, and phospho-ATG16L1. The cKO of HMGB1 in rods increased the expression of Fas and the Bax/Bcl-2 ratio in detached retinas, promoting apoptotic cell death. In conclusion, endogenous HMGB1 facilitates autophagy activation in PR cells following RD to promote PR cell survival and reduce programmed apoptotic cell death.

Temporally independent association of multiple evanescent white dot syndrome and optic neuritis.

PURPOSE: To describe three patients that developed temporally distinct episodes of optic neuritis and multiple evanescent white dot syndrome (MEWDS). METHODS: We retrospectively reviewed the medical records and imaging studies of three women evaluated at a tertiary referral center for both optic neuritis and MEWDS. RESULTS: Three otherwise healthy women, aged 17, 36, and 41, developed temporally separated episodes of optic neuritis and MEWDS. The time periods between the two events were 3, 48, and 60 months, and in two of the three cases, the optic neuritis event preceded the episode of MEWDS. No patient endorsed prodromal flu-like symptoms prior to developing vision loss. The mean presenting visual acuities were better with the optic neuritis episode (LogMAR 0.360, Snellen 20/46) than with retinal event (LogMAR 0.684, Snellen 20/97). All three patients had improvement in vision, with mean visual acuity of 20/29 (LogMAR 0.165) at last follow-up. One patient later developed idiopathic noninfectious posterior uveitis and another developed multiple sclerosis requiring treatment. CONCLUSION: While a rare association, patients can develop both optic neuritis and MEWDS within the same eye at different time points. It is unknown whether such patients are at even higher risk of developing systemic autoimmune disease than are patients with either MEWDS or optic neuritis alone.