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.].

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.

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.

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.].

Risk Factors for Endophthalmitis Following Open Globe Injuries: A 17-Year Analysis.

BACKGROUND/AIMS: To determine the rate of endophthalmitis and assess risk factors for development of endophthalmitis following open globe injury (OGI). METHODS: A retrospective chart review of all patients treated for OGI at the University of Michigan from January 2000 to July 2017 was conducted. Exclusion criteria included intravitreal injection or intraocular surgery in the 30 days prior to injury or less than 30 days of follow-up. A total of 586 out of 993 open globe injuries were included in the study. The main outcome measure was the rate of endophthalmitis. RESULTS: In this study, 25/586 eyes (4.3%) had endophthalmitis. Of these, 12/25 eyes (48.0%) presented with endophthalmitis and 13/25 eyes (52.0%) developed endophthalmitis after globe closure. Multivariate analysis identified time to globe repair (OR 4.5, CI 1.9-10.7, p = 0.0008), zone I injury (OR 3.6, CI 1.1-11.0, p = 0.0282), and need for additional surgery (OR 5.5, CI 1.5-19.7, p = 0.0092) as factors associated with increased risk of developing endophthalmitis. Subconjunctival antibiotic injection at the time of globe closure (OR 0.3, CI 0.1-0.7, p = 0.0036) was associated with decreased risk of developing endophthalmitis. CONCLUSION: Prompt globe closure and subconjunctival antibiotics may reduce the risk of endophthalmitis in OGI. Furthermore, our practice of a one-time dose of systemic prophylactic antibiotics, and intravitreal antibiotics if intraocular foreign body (IOFB) removal is delayed, was not found to increase the rate of endophthalmitis.

Surgical repair of primary non-complex rhegmatogenous retinal detachment in the modern era of small-gauge vitrectomy.

OBJECTIVE: To report anatomic and visual outcomes of pars plana vitrectomy (PPV), as well as scleral buckling (SB) and PPV/SB as surgical treatments for the management of primary, non-complex rhegmatogenous retinal detachment (RRD). METHODS AND ANALYSIS: Data from 751 eyes that underwent PPV, SB or combined PPV/SB as a surgical treatment for primary non-complex RRD with at least 3 months of follow-up were analysed to determine rates of single surgery anatomic success (SSAS) and final anatomic success (FAS). Patients or the public were not involved in the design, conduct or reporting of this research. RESULTS: PPV accounted for 89.0% (n=668), PPV/SB for 6.8% (n=51) and SB for 4.2% (n=32) cases. Overall SSAS (91.2% PPV, 84.3% PPV/SB, 93.8% SB; p=0.267) and FAS (96.7% PPV, 94.1% PPV/SB and 100.0% SB; p=0.221) were reported for the three surgical groups. SSAS and FAS were similar for lens status, macular detachment status and the presence or absence of inferior retinal breaks for each of the PPV, PPV/SB and SB groups. CONCLUSIONS: In this large, single institution, retrospective case series, we report surgical outcomes for patients with primary non-complex RRD managed with PPV, SB or PPV/SB in the modern era of small-gauge vitrectomy. We demonstrate that primary PPV without adjunct SB provides excellent anatomic and visual outcomes irrespective of lens status, macular involvement or pathology location.

Contemporary Management of Complex and Non-Complex Rhegmatogenous Retinal Detachment Due to Giant Retinal Tears.

PURPOSE: To investigate the clinical features and surgical outcomes of rhegmatogenous retinal detachment (RRD) associated with giant retinal tears (GRTs) at a tertiary referral center. PATIENTS AND METHODS: A retrospective, non-consecutive interventional case series of GRT-associated RRDs that underwent primary surgical repair at the University of Michigan W.K. Kellogg Eye Center between January 1, 2011 and July 1, 2020. Clinical characteristics and preoperative, perioperative, and postoperative data were collected. RESULTS: Forty-eight eyes of 47 patients with GRT-associated RRDs met inclusion criteria, including those that were children (under 12 years, N=4, 8.3%), associated with a history of trauma (N=20, 41.7%) or with grade C proliferative vitreoretinopathy (PVR-C) (N=7, 14.6%) at baseline. Median age was 46 years (interquartile range (IQR): 29 years, range: 4 to 72 years), median follow-up was 28 months (IQR: 43 months, range: 3-124 months), and 83.3% (N=40) of subjects were male. Primary surgical repair for GRT-associated RRDs included pars plana vitrectomy (PPV) (N=40, 83.3%), scleral buckle (SB) (N=1, 2.1%), or combined PPV/SB (N=7, 14.6%). Surgical approach commonly involved the use of perfluorocarbon liquid (N=43, 90%) and gas tamponade (N=39, 81%). Single surgery anatomic success (SSAS) was 75% (95% CI: 60%, 85%) at 3 months and 65% (95 CI: 47%, 78%) at 2 years. Final anatomic success was achieved in all 48 eyes (100%). Median visual acuity improved from 20/250 preoperatively to 20/60 at final follow-up, with 44% (N=20) of eyes achieving postoperative visual acuity of 20/40 or better. CONCLUSION: In this series from a tertiary referral center, both complex and non-complex GRT-associated RRDs were most commonly managed with PPV alone, perfluorocarbon liquid, and gas tamponade with favorable final anatomic and visual outcomes comparable to other modern GRT series.

Measuring Contrast Sensitivity Function With Active Learning in Retinal Vein Occlusion: A New Endpoint of Visual Function.

BACKGROUND AND OBJECTIVE: To characterize contrast sensitivity function (CSF) in patients with retinal vein occlusion (RVO) compared to age-matched controls using novel computerized contrast sensitivity (CS) testing with active learning algorithms. PATIENTS AND METHODS: CSF was prospectively measured in RVO patients with visual acuity (VA) greater than 20/200 and age-matched controls using the novel Manifold Contrast Vision Meter implementing quantitative CSF testing. Outcomes included area under the Log CSF (AULCSF), contrast acuity (CA), and CS thresholds at 1, 1.5, 3, 12, and 18 cycles per degree (cpd). A sub-analysis was performed on RVO eyes with good acuity (VA ≥ 20/30). RESULTS: Twenty-two eyes with RVO and 63 control eyes were included. Mean AULCSF (± standard deviation) in RVO eyes was 0.817 (0.28) compared to 1.217 (0.28) in controls (P < .0001). Mean contrast acuity in the RVO group was 1.054 (0.19) versus 1.286 ± 0.16 in controls (P < .0001). For individual spatial frequencies, CS loss at 6.0 cpd was most prominent in the RVO group. In 10 RVO eyes with VA of 20/30 or greater, mean AULCSF was 0.978 versus 1.217 in control eyes. (P = .008). CONCLUSIONS: CSF in eyes with RVO was found to be significantly reduced compared to age-matched controls. CSF seems to be a promising visual function endpoint with potential applications in clinical practice and future clinical trials. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:392-400.].

Randomized Safety and Feasibility Trial of Ultra-Rapid Cooling Anesthesia for Intravitreal Injections.

PURPOSE: To test the safety and preliminary efficacy of rapid, nonpharmacologic anesthesia via cooling for intravitreal injections. DESIGN: Single-center, randomized phase 1 dose-ranging safety study (ClinicalTrials.gov identifier, NCT02872012). PARTICIPANTS: Adults 18 years of age or older with a diagnosis of exudative macular degeneration or diabetic macular edema requiring bilateral anti-vascular endothelial growth factor therapy were included. METHODS: A handheld device was developed to provide anesthesia via cooling to a focal area on the surface of the eye before intravitreal treatment (IVT). In 22 patients undergoing bilateral IVT, 1 eye was randomized to receive standard of care (SOC) lidocaine-based anesthesia and the other eye received cooling-anesthesia at 1 of 5 different temperatures and cooling times. Subjective pain was assessed via the visual analog scale (VAS; range, 1-10) at 2 time points: (1) immediately after IVT and (2) 4 hours after IVT. Treated eyes were assessed for ocular safety 24 hours after IVT. MAIN OUTCOME MEASURES: We determined the occurrence of adverse events in eyes treated with cooling anesthesia. Mean VAS pain scores immediately after IVT and 4 hours after IVT in eyes receiving cooling anesthesia were compared with eyes receiving SOC. RESULTS: A total of 44 eyes were treated, 22 with cooling anesthesia and 22 with SOC. No dose-related toxicity was found with cooling anesthesia. Mild, transient adverse events were recorded in 32% of patients treated with cooling anesthesia versus 44% of patients receiving SOC. The mean±standard error of the mean (SEM) VAS pain scores immediately after intravitreal injection were 2.3 ± 0.4 for patients receiving SOC and 2.2 ± 0.6 in patients receiving -10° C cooling anesthesia (P = 0.8). Mean±SEM pain scores 4 hours after injection were 1.6 ± 0.4 for SOC and 1.2 ± 0.5 in the combined -10° C arms (P = 0.56). Total mean±SEM procedure time was 124 ± 5 seconds for patients treated with cooling anesthesia versus 395 ± 40 seconds for SOC (P < 0.0001). CONCLUSIONS: Ultra-rapid cooling of the eye for anesthesia was well tolerated, with -10° C treatment resulting in comparable levels of anesthesia to SOC with a reduction in procedure time.

ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.

PURPOSE: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. METHODS: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. RESULTS: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. CONCLUSION: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.

Rationale for American Society of Retina Specialists Best Practice Recommendations for Conducting Vitreoretinal Surgery during the COVID-19 Era.

PURPOSE: To detail the rationale behind recommendations recently published by the American Society of Retina Specialists (ASRS) outlining best practices for safety of vitreoretinal surgeons and staff while performing vitreoretinal surgery during the coronavirus disease (COVID)-19 pandemic. METHODS: The committee for ASRS Best Practices for Retinal Surgery during the COVID-19 Pandemic reviewed existing evidence and information on SARS-CoV-2 transmission, and risk factors during vitreoretinal surgery. Recommendations were based on best available published data, cumulative clinical experiences, and recommendations and policies from other organizations. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the strength of recommendations and confidence in the evidence. These serve as interim recommendations which are routinely updated given gaps of knowledge and lack of high-quality data on this evolving subject. RESULTS: Relevant existing literature related to methods of transmission, and ocular manifestations of SARS-CoV-2 are summarized. The data and clinical experiences driving recommendations for pre-operative, intraoperative and post-operative surgical considerations, anesthesia choice, as well as considerations for intravitreal injections are provided. CONCLUSION: Recommendations are provided with the goal of protecting vitreoretinal surgeons and associated personnel from exposure to SARS-CoV-2 during interventional vitreoretinal procedures. This is a rapidly evolving topic with numerous remaining gaps in our current knowledge. As such, recommendations will evolve and the current manuscript is intended to serve as a foundation for continued dialogue on best practices.

A small peptide antagonist of the Fas receptor inhibits neuroinflammation and prevents axon degeneration and retinal ganglion cell death in an inducible mouse model of glaucoma.

BACKGROUND: Glaucoma is a complex, multifactorial disease where apoptosis, microglia activation, and inflammation have been linked to the death of retinal ganglion cells (RGCs) and axon degeneration. We demonstrated previously that FasL-Fas signaling was required for axon degeneration and death of RGCs in chronic and inducible mouse models of glaucoma and that Fas activation triggered RGC apoptosis, glial activation, and inflammation. Here, we investigated whether targeting the Fas receptor with a small peptide antagonist, ONL1204, has anti-inflammatory and neuroprotective effects in a microbead-induced mouse model of glaucoma. METHODS: Intracameral injection of microbeads was used to elevate intraocular pressure (IOP) in Fas-deficient (Faslpr) mice and WT C57BL/6J mice that received an intravitreal injection of the Fas inhibitor, ONL1204 (2 µg/1 µl) (or vehicle only), on day 0 or day 7 after microbead injection. The IOP was monitored by rebound tonometry, and at 28 days post-microbead injection, Brn3a-stained RGCs and paraphenylenediamine (PPD)-stained axons were analyzed. The effects of ONL1204 on retinal microglia activation and the expression of inflammatory genes were analyzed by immunostaining of retinal flatmounts and quantitative PCR (qPCR). RESULTS: Rebound tonometry showed equivalent elevation of IOP in all groups of microbead-injected mice. At 28 days post-microbead injection, the RGC and axon counts from microbead-injected Faslpr mice were equivalent to saline-injected (no IOP elevation) controls. Treatment with ONL1204 also significantly reduced RGC death and loss of axons in microbead-injected WT mice when compared to vehicle-treated controls, even when administered after IOP elevation. Confocal analysis of Iba1-stained retinal flatmounts and qPCR demonstrated that ONL1204 also abrogated microglia activation and inhibited the induction of multiple genes implicated in glaucoma, including cytokines and chemokines (GFAP, Caspase-8, TNFα, IL-1ß, IL-6, IL-18, MIP-1α, MIP-1ß, MIP-2, MCPI, and IP10), components of the complement cascade (C3, C1Q), Toll-like receptor pathway (TLR4), and inflammasome pathway (NLRP3). CONCLUSIONS: These results serve as proof-of-principal that the small peptide inhibitor of the Fas receptor, ONL1204, can provide robust neuroprotection in an inducible mouse model of glaucoma, even when administered after IOP elevation. Moreover, Fas signaling contributes to the pathogenesis of glaucoma through activation of both apoptotic and inflammatory pathways.

Vitreous Cytokine Expression and a Murine Model Suggest a Key Role of Microglia in the Inflammatory Response to Retinal Detachment.

Purpose: Retinal detachment (RD) separates the retina from the underlying retinal pigment epithelium, resulting in a gradual degeneration of photoreceptor (PR) cells. It is known that RD also results in an inflammatory response, but its contribution to PR degeneration is unknown. In this study we examine the inflammatory responses to RD in patient vitreous and validate a mouse experimental RD as a model of this phenomenon. Methods: Multiplex bead arrays were used to examine cytokine levels in vitreous samples from 24 patients with macula-off rhegmatogenous retinal detachment (RRD) undergoing reattachment surgery and from 10 control patients undergoing vitrectomy for vitreous opacities or epiretinal membrane. Activation of the innate immune response was then examined in a mouse model of RD. Results: Twenty-eight factors were significantly increased in vitreous from RD patients versus controls. Notable were the cytokines MCP-1 (CCL2), IP-10 (CXCL10), fractalkine (CX3CL1), GRO (CXCL1), MDC (CCL22), IL-6, and IL-8, which all exhibited relatively high concentrations and several-fold increases in the vitreous of RD patients. Concentrations of various analytes correlated with a range of clinical variables such as duration of detachment and visual acuity. Retinal detachment in the mouse resulted in cytokine mRNA expression changes consistent with human RD vitreous results, as well as microglial proliferation and migration toward the outer retina. Conclusions: The findings suggest that an inflammatory response involving microglia is a component of the reaction to retinal detachment that may impact visual acuity after surgical repair and that mouse experimental RD can serve as a model to study this effect.

Persistent macular puckering following excision of causative orbital tumor.

PURPOSE: To describe the clinical course of a patient with a retrobulbar orbital tumor causing myopic shift and macular pucker. OBSERVATION: Following complete surgical removal of a retrobulbar orbital cavernous hemangioma, the myopic shift improved but the macular pucker persisted even 3 years after orbital surgery, with no sign of tumor recurrence. CONCLUSION AND IMPORTANCE: Chorioretinal folds secondary to chronic mechanical force from an orbital tumor may persist long after the tumor is removed. This case may assist ophthalmologists in their discussions with, and counseling of, patients regarding visual prognosis following excision of orbital tumors that are causing retinal changes.

NOVEL CLASSIFICATION SYSTEM FOR COMBINED HAMARTOMA OF THE RETINA AND RETINAL PIGMENT EPITHELIUM.

PURPOSE: To develop an anatomical classification scheme for combined hamartoma of the retina and retinal pigment epithelium (RPE) and specify recommendations for follow-up interval. METHODS: Retrospective review of patients with combined hamartoma of the retina and RPE examined during a 7-year period (2008-2015). The clinical presentation, fundus examination, and optical coherence tomography were analyzed. RESULTS: Lesions were classified based on location, fundus features, and optical coherence tomography findings. Lesion location: macular/peripapillary-Zone 1; mid-periphery-Zone 2; and far periphery-Zone 3. Associated fundus findings: no retinal traction-Stage 1; retinal traction and/or retinoschisis-Stage 2; and retinal detachment-Stage 3. Optical coherence tomography findings: epiretinal component only-A; partial retinal involvement-B; and complete retinal and RPE involvement-C. Complete ophthalmologic evaluation is recommended at least every 6 months for patients younger than 12 years, with more frequent follow-up in patients with: lesions in the macula/peripapillary (Zone 1) or with retinal traction, retinoschisis, or retinal detachment (Stage 2 and 3). Surgical intervention is recommended in patients with vision loss secondary to macular traction or retinal detachment. CONCLUSION: A new clinical classification system is proposed for evaluating and managing patients with combined hamartoma of the retina and RPE. The zone and stage of combined hamartoma of the retina and RPE lesion will assist in determining follow-up interval and surgical intervention. Application of a uniform classification scheme will facilitate assessment and comparison of findings across different studies.

POSTOPERATIVE ENDOPHTHALMITIS CAUSED BY BOSEA THIOOXIDANS.

PURPOSE: To report an unusual case of postcataract endophthalmitis secondary to Bosea thiooxidans. METHODS: Case report. RESULTS: An 86-year-old man presented with postoperative endophthalmitis 3 weeks after uncomplicated cataract surgery. He complained of a headache and blurry vision but denied having eye pain. Slit-lamp examination demonstrated leukocytes with a fibrinous membrane in the anterior segment and vitritis. A diagnosis of acute postoperative endophthalmitis was made, and the patient was treated with intravitreal antibiotics. Culture of vitreous tap revealed Bosea thiooxidans, a gram-negative rod found in soil and water systems. CONCLUSION: To our knowledge, this report is the first to describe Bosea thiooxidans endophthalmitis and one of a few reports of human infection with this microbial agent.

FAS apoptotic inhibitory molecule 2 is a stress-induced intrinsic neuroprotective factor in the retina.

We report the neuroprotective role of FAS apoptotic inhibitory molecule 2 (FAIM2), an inhibitor of the FAS signaling pathway, during stress-induced photoreceptor apoptosis. Retinal detachment resulted in increased FAIM2 levels in photoreceptors with higher amounts detected at the tips of outer segments. Activation of FAS death receptor via FAS-ligand led to JNK-mediated FAIM2 phosphorylation, decreased proteasome-mediated degradation and increased association with the FAS receptor. Photoreceptor apoptosis was accelerated in Faim2 knockout mice following experimental retinal detachment. We show that FAIM2 is primarily involved in reducing stress-induced photoreceptor cell death but this effect was transient. FAIM2 was found to interact with both p53 and HSP90 following the activation of the FAS death pathway and FAIM2/HSP90 interaction was dependent on the phosphorylation of FAIM2. Lack of FAIM2 led to increased expression of proadeath genes Fas and Ripk1 in the retina under physiologic conditions. These results demonstrate that FAIM2 is an intrinsic neuroprotective factor activated by stress in photoreceptors and delays FAS-mediated photoreceptor apoptosis. Modulation of this pathway to increase FAIM2 expression may be a potential therapeutic option to prevent photoreceptor death.