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The Ebola virus disease (EVD) outbreak of 2013–2016 was large, leaving in its wake an estimated 17,000 survivors in West Africa. Uveitis is one of the most common ophthalmic manifestations of EVD, but long-term follow-up in the at-risk population is lacking. We conducted a retrospective cross-sectional study of 521 EVD survivors from Sierra Leone who underwent comprehensive ophthalmic examination a median of 1,289 days, or ≈3.5 years, after discharge from Ebola treatment units. The most common ophthalmic findings were cataracts (117 eyes, 11.2%), uveitis (86 eyes, 8.3%), dry eyes (81 eyes, 7.8%), and chorioretinal scar (68 eyes, 6.5%). EVD survivors with cataracts, uveitis, optic neuropathy, and corneal scar were more likely to have vision impairment, defined as Snellen visual acuity worse than 20/50. Results of our study highlight the need for ongoing vision care in EVD survivors.

Coronavirus disease 2019 (COVID-19) is associated with increased risk of microvascular complications; however, reports of ophthalmic manifestations associated with retinal vascular occlusion associated with COVID-19 are limited. In this report, we describe two middle-aged female patients who were admitted for acute hypoxic respiratory failure secondary to COVID-19-induced pneumonia. Following prolonged intensive care unit admission requiring mechanical ventilation and critical care interventions, both patients reported substantially reduced vision upon regaining consciousness. Dilated funduscopic exam showed multiple blot hemorrhages in all quadrants of the posterior pole, bilateral retinal hemorrhage, macular edema, and retinal vascular tortuosity. Both patients were diagnosed with retinal ischemic events owing to bilateral ophthalmic artery occlusion in the first patient, and bilateral central retinal vein occlusion (CRVO) in the second individual. While uncommon, retinal microvascular complications associated with COVID-19 leading to vision loss require prompt evaluation and referral given their potential long-term impact following acute illness.

Intraocular foreign bodies (IOFBs) remain a severe complication of ocular trauma commonly encountered worldwide. This literature review aimed to discuss current practice patterns, areas of controversy, and advances in the management of IOFBs. Injuries involving IOFBs carry significant ocular morbidity and management can be extremely challenging. A systematic approach to preoperative evaluation and IOFB surgical management is detailed in this article and should be applied in each case. The location and composition of an IOFB have important implications on surgical approach and timing, especially in cases of toxic metals and vegetable matter. The advantages, disadvantages, and previous literature regarding immediate versus delayed foreign body removal are presented. Surgical approaches are described, with an emphasis on posterior chamber IOFB management and removal via pars plana vitrectomy. Final visual acuity is variable, but approaches have been used to prognosticate outcomes including the Ocular Trauma Score. By synthesizing current IOFB literature, the goal is to provide practitioners with guidance that will maximize the chances of surgical success and patient outcomes.

Objectives: To determine the associated pathogen during the 2023 conjunctivitis outbreak in Vietnam Methods: RNA-sequencing was used to identify pathogens before and during the outbreak. Results: 24 patients with infectious conjunctivitis between March and October 2023 from Hai Yen Vision Institute in Vietnam were swabbed. Coxsackievirus A24v was the most common pathogen identified. Phylogenetic analysis of these strains demonstrates similarities to the Coxsackievirus identified in the 2022 India outbreak. Human adenovirus D was also circulating. Ocular findings of tearing, purulence, and itching were common in this outbreak. Conclusions: Multiple viruses can co-circulate during conjunctivitis outbreaks. Hemorrhagic conjunctivitis, commonly associated with coxsackievirus conjunctivitis, was not a common clinical sign in this outbreak. Repeat genetic surveillance, with the notable inclusion of RNA virus detection strategies, is important for outbreak detection.

Abstract Purpose To report a case of primary vitreoretinal lymphoma masquerading as infectious retinitis that was diagnosed via a retinal biopsy. Observations A 72-year-old female patient was referred to our ophthalmology clinic for evaluation of retinitis and vasculitis in the right eye (OD). On examination, best-corrected visual acuities (BCVAs) were hand motions OD and 20/20 in the left eye (OS). Fundus examination revealed optic disc edema and diffuse retinal whitening superior to the superotemporal arcade OD. Given the high suspicion of infectious retinitis, the patient was treated with intravitreal foscarnet, systemic acyclovir, and oral prednisone and underwent a comprehensive uveitis workup, which was unremarkable for viral and autoimmune entities. Given the patient’s history of diffuse large B cell lymphoma with cutaneous involvement, vitreoretinal lymphoma was suspected, prompting pars plana vitrectomy with a retinal biopsy. Biopsy and immunohistochemistry results were consistent with B-cell lymphoma, and the patient was treated with high-dose methotrexate and rituximab. At 5-month follow-up, BCVAs were hand motions OD and 20/30 OS, and fundus examination demonstrated disc edema with resolution of retinal whitening OD. She responded well to the treatment with regression of vitreoretinal lymphoma on examination and is being monitored closely for lymphoma recurrence. Conclusions and importance Although uncommon, patients with vitreoretinal lymphoma may masquerade as infectious retinitis, and vitreoretinal lymphoma should be suspected when refractory to antiviral therapy and in the setting of a negative workup for viral etiologies. Vitrectomy with retinal biopsy may be considered to aid the diagnosis of vitreoretinal lymphoma although careful consideration of the risks and benefits is warranted.

We report the case of a 71-year-old man who presented 2 years following renal transplantation with diffuse, unilateral cytomegalovirus retinitis five weeks after receiving an intravitreal dexamethasone implant device for the management of central retinal vein occlusion. Examination of the left eye showed diffuse retinal hemorrhages, attenuated and tortuous retinal vessels, and superior retinal whitening. The patient was successfully treated with serial intravitreal foscarnet injections and oral valganciclovir with disease regression observed by 12 weeks after presentation. The patient’s visual acuity and examination remained stable at 9-months follow-up.

Childhood blindness is an issue of global health impact, affecting approximately 2 million children worldwide. Vision 2020 and the United Nations Sustainable Development Goals previously identified childhood blindness as a key issue in the twentieth century, and while public health measures are underway, the precise etiologies and management require ongoing investigation and care, particularly within resource-limited settings such as sub-Saharan Africa. We systematically reviewed the literature on childhood blindness in West Africa to identify the anatomic classification and etiologies, particularly those causes of childhood blindness with systemic health implications. Treatable causes included cataract, refractive error, and corneal disease. Systemic etiologies identified included measles, rubella, vitamin A deficiency, and Ebola virus disease. While prior public health measures including vitamin A supplementation and vaccination programs have been deployed in most countries with reported data, multiple studies reported preventable or reversible etiologies of blindness and vision impairment. Ongoing research is necessary to standardize reporting for anatomies and/or etiologies of childhood blindness to determine the necessity of further development and implementation of public health measures that would ameliorate childhood blindness and vision impairment.

As technology continues to evolve, the possibility for a wide range of dangers to people, organizations, and countries escalate globally. The United States federal government classifies types of threats with the capability of inflicting mass casualties and societal disruption as Chemical, Biological, Radiological, Nuclear, and Energetics/Explosives (CBRNE). Such incidents encompass accidental and intentional events ranging from weapons of mass destruction and bioterrorism to fires or spills involving hazardous or radiologic material. All of these have the capacity to inflict death or severe physical, neurological, and/or sensorial disabilities if injuries are not diagnosed and treated in a timely manner. Ophthalmic injury can provide important insight into understanding and treating patients impacted by CBRNE agents; however, improper ophthalmic management can result in suboptimal patient outcomes. This review specifically addresses the biological agents the Center for Disease Control and Prevention (CDC) deems to have the greatest capacity for bioterrorism. CBRNE biological agents, encompassing pathogens and organic toxins, are further subdivided into categories A, B, and C according to their national security threat level. In our compendium of these biological agents, we address their respective CDC category, systemic and ophthalmic manifestations, route of transmission and personal protective equipment considerations as well as pertinent vaccination and treatment guidelines.

Purpose: To describe the novel application of a urological instrument, the nitinol stone basket, in the removal of a retained intraocular foreign body (IOFB). Observations: This is a retrospective case series describing two eyes of two patients presenting with metallic IOFBs after hammering metal-on-metal. Both patients underwent 23-gauge pars plana vitrectomy (PPV) and successful IOFB extraction using the NCircle® Nitinol Tipless Stone Extractor. There were no intraoperative or post-surgical complications. Both patients demonstrated improvement in vision, with most recent postoperative visual acuities of 20/40 and 20/60. Conclusions and importance: The nitinol stone basket may be considered for removal of IOFBs, particularly larger IOFBs that are difficult to grasp with forceps. Our cases add to the literature showing favorable visual outcomes and few complications in the post-operative period using this technique.

Chemical agents have been utilized for centuries in warfare and pose a health threat to civilians and military personnel during armed conflict. Despite treaties and regulations against their use, chemical agent exposure remains a threat and measures to understand their effects and countermeasures for systemic and organ-specific health are needed. Many of these agents have ocular complications, both acute and chronic. This mini-review focuses on key chemical agents including vesicants (mustards, lewisite), nerve agents (sarin, VX), knockdown gasses (hydrogen cyanide), and caustics (hydrofluoric acid). Their ophthalmic manifestations and appropriate treatment are emphasized. Acute interventions include removal of the source and meticulous decontamination, as well as normalization of pH to 7.2–7.4 if alteration of the ocular pH is observed. Besides vigorous lavage, acute therapies may include topical corticosteroids and non-steroid anti-inflammatory therapies. Appropriate personal protective equipment (PPE) and strict donning and doffing protocols to avoid healthcare provider exposure are also paramount in the acute setting. For more severe disease, corneal transplantation, amniotic membrane graft, and limbal stem cell transplantation may be needed. Orbital surgery may be required in patients in whom cicatricial changes of the ocular surface have developed, leading to eyelid malposition. Multidisciplinary care teams are often required to handle the full spectrum of findings and consequences associated with emerging chemical threats.

Deep characterization of uveitis in a rhesus monkey confirms Ebola virus RNA persistence is associated with severe immunopathology in the eye, with broader implications for the prevention and treatment of sight-threatening uveitis in human survivors of Ebola virus.

Abstract Background Primary vitreoretinal lymphoma (PVRL) is an aggressive lymphoma that may present with protean features and represents a diagnostic challenge. Given that patients with PVRL are at high risk of CNS involvement with a high mortality and morbidity rate, prompt diagnosis is crucial to initiate treatment early in the disease course. A multimodality imaging approach including fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), fluorescein and indocyanine angiography, and electroretinography (ERG) can provide information to establish a diagnosis and provide objective measures for management. We review key findings seen via these imaging modalities in patients with PVRL. Observations Fundus photography can highlight commonly seen patterns of PVRL including vitritis, subretinal disease, retinal pigment epithelial (RPE) abnormalities, optic nerve edema, retinal detachment, and less typical retinitis-like lesions. FAF can identify characteristic patterns of hyper- and hypoautofluorescent signal abnormalities in the macula. Spectral-domain OCT will demonstrate vitreous cells, RPE nodularity, and hyperreflectivity of the outer retina. The presence of a hyper-reflective band in the subretinal space and infiltrates between the RPE and Bruch’s membrane can assist in distinguishing PVRL from choroidal lymphoma. Vertical hyperreflective columns (VHRLs) are another pertinent finding that may represent microinfiltrates of the tumor. OCT has proven to be a particularly useful modality in assessing the progress of treatment in PVRL. Fluorescein angiography can show RPE changes, which include granularity, late staining at the RPE level, and blockage. Indocyanine green angiography (ICGA) primarily shows hypocyanescence, which corresponds to PVRL lesions on fundus photography and may occur secondary to loss of RPE and choriocapillaris. Conclusion While PVRL remains a challenging disease to diagnose and follow, the use of a multimodality imaging approach may assist in establishing a diagnosis. Because of the anatomic spaces PVRL may affect, fundus photography, OCT, FAF, angiography, and ERG can identify key characteristics of the disease, differentiate PVRL from other diseases, and provide baseline information for targeted systemic and local therapies. Further assessment of anatomic and functional targets will aid our clinical application of multimodal imaging in the management of PVRL.

Early diagnosis of infectious uveitis can lead to prompt initiation of treatment to minimize vision-threatening sequelae. As various infectious etiologies of uveitis share similar clinical features, advancements in polymerase chain reaction (PCR) and metagenomic next-generation sequencing (MDS) have shown significant promise in improving diagnostic capabilities. Various techniques of PCR, including real-time, multiplex, comprehensive, and broad-range, have increased the armamentarium for infectious uveitis diagnosis. Additionally, metagenomic deep sequencing technology has provided a methodology to identify causative pathogens as well as novel etiologies of uveitis. This review discusses the diagnostic tools available for infectious uveitis and highlights the advantages and disadvantages of the techniques.

Methamphetamine use has become a rampant public health issue that not only causes devastating consequences to the user but also poses a burden to surrounding communities. A spectrum of ophthalmic sequelae is associated with methamphetamine use and includes episcleritis, scleritis, corneal ulceration, panophthalmitis, endophthalmitis, retinal vasculitis, and retinopathy. In many instances, prompt recognition of the condition and associated infectious process and early initiation of antimicrobial therapy are crucial steps to preventing vision loss. In this review, we summarize the reported ocular complications that may result from methamphetamine use in addition to several postulated mechanisms regarding the ocular toxicity of methamphetamine. The increasing prevalence of methamphetamine use as a public health threat highlights the need for continued investigation of this ophthalmologic issue.

Abstract Purpose To describe the visual acuity and anatomic outcomes of intravitreal methotrexate (MTX) for the treatment of primary vitreoretinal lymphoma (PVRL). Methods Single-center retrospective case series of patients with a diagnosis of PVRL treated with intravitreal MTX. Patient records were reviewed for demographic information, ocular exam findings, and treatment regimens including number of MTX injections. Clinical outcomes recorded included visual acuity (VA), time to partial (PR) or complete response (CR), disease-free survival, time to relapse, and any CNS progression. Results Ten eyes of 7 patients (4 male, 6 female) were reviewed. The mean age ± standard deviation (SD) was 70 ± 12 years. Five patients had prior or concomitant diagnosis of primary CNS lymphoma with a history of systemic chemotherapy including MTX. Three eyes (30%) exhibited isolated vitreous involvement, four (40%) had subretinal lesions, and three (30%) presented with both vitreous and subretinal disease. Mean initial logMAR VA was 0.38 ± 0.52 (Snellen visual equivalent 20/50), while mean final logMAR VA ± SD was 0.34 ± 0.27 (Snellen visual equivalent 20/40) with a mean follow-up time of 26 months (Range, 3–49 months). Patients received an average of 6 intravitreal MTX injections (Range 1–10) over the course of treatment. Two patients received concomitant systemic chemotherapy. Mean time to either PR or CR was 57 days, and 6 eyes (60%) exhibited regression with no relapse after local treatment. For the 4 eyes that eventually relapsed, the mean time ± SD to first relapse was 193 days ± 155 days, and one eye experienced a second relapse. Two of 3 patients with subretinal disease showed complete regression with extended follow-up of 1 and 4 years following treatment with less than 3 doses of intravitreal MTX. One patient with PVRL developed CNS lymphoma during the study period. VA remained stable overall between the initial treatment visit, 3, 6, and 12-months (P > 0.05 for paired comparisons of VA over time). Conclusions Intravitreal methotrexate was well-tolerated and led to local disease response in the majority of patients at approximately 2 months after initiation of treatment of intraocular lymphoma. Further studies on the efficacy of intravitreal treatment alone versus combined systemic and intravitreal treatment are warranted.

Abstract Background Intraocular lymphoma accounts for fewer than 1% of intraocular tumors. When the posterior segment is involved, it can be further classified as vitreoretinal or choroidal lymphoma. Vitreoretinal lymphoma (VRL) can rarely masquerade as an infectious retinitis making diagnosis and management challenging. Results A 73-year-old woman with a history of non-central nervous system (CNS) involving diffuse large B-cell lymphoma (DLBCL) was referred for worsening blurry vision—visual acuity of count figures at 2 ft—in her right eye for 8 months. Dilated fundus examination of the right eye was significant for retinal whitening and dot-blot hemorrhages, which was concerning for a viral retinitis and guided initial management. Secondary intraocular lymphoma was also considered. The retinal disease continued to progress despite intravitreal and systemic antiviral therapy, and a diagnostic vitrectomy was inconclusive. A retinal biopsy was then performed, which showed DLBCL, confirming a diagnosis of secondary VRL. Three subsequent treatments with intravitreal methotrexate led to regression of the VRL. Conclusions Our case highlights the utility of a retinal biopsy after an inconclusive diagnostic vitrectomy in a challenging scenario of VRL to establish a diagnosis and initiate successful treatment. A multidisciplinary team of providers was essential for diagnosis, comprehensive workup, medical and surgical management of the patient.

Introduction Vitreoretinal lymphoma is a rare ocular cancer with high morbidity and mortality despite treatment. Diagnosis by cytopathology is often delayed, and various molecular and image-based investigations have been developed. Diverse treatments are used, but there is a limited medical evidence to differentiate their effectiveness. We designed an international registry that would collect diagnostic, treatment and outcomes data, to establish new evidence for the management of this cancer.Methods and analysis The International Vitreoretinal B-Cell Lymphoma Registry will accrue data retrospectively for individuals aged 18 years or older, diagnosed with new or recurrent vitreoretinal B-cell lymphoma on or after 1 January 2020. A steering committee of subspecialised ophthalmologists identified 20 key clinical data items that describe patient demographics, tissue involvements, diagnostic testing, ocular and systemic treatments and treatment complications, and visual acuity and survival outcomes. Customised software was designed to permit collection of these data across a single baseline and multiple follow-up forms. The platform collects data without identifiers and at 3 month reporting intervals. Outcomes of the project will include: (1) descriptions of clinical presentations, and diagnostic and therapeutic preferences; (2) associations between clinical presentations, and diagnostics and treatments, and between diagnostics and treatments (assessed by ORs with 95% CIs); and (3) estimations of rates of vision loss, and progression-free and overall survival (assessed by Kaplan-Meier estimates).Ethics and dissemination The registry has received Australia-wide approval by a national human research ethics committee. Sites located outside Australia are required to seek local human research ethics review. Results generated through the registry will be disseminated primarily by peer-reviewed publications that are expected to inform clinical practice, as well as educational materials.

Summary: Background: Ebola virus disease (EVD) outbreaks in West Africa (2013-2016) and the Democratic Republic of Congo (2018-2020) have resulted in thousands of EVD survivors who remain at-risk for survivor sequelae. While EVD survivorship has been broadly reported in adult populations, pediatric EVD survivors are under-represented. In this cross-sectional study, we investigated the prevalence of eye disease, health-related quality-of-life, vision-related quality-of-life, and the burden of mental illness among pediatric EVD survivors in Sierra Leone. Methods: Twenty-three pediatric EVD survivors and 58 EVD close contacts were enrolled. Participants underwent a comprehensive ophthalmic examination and completed the following surveys: Pediatric Quality of Life Inventory Version 4.0, Effect of Youngsters Eyesight on Quality-of-Life, and the Revised Child Anxiety and Depression Scale. Findings: A higher prevalence of uveitis was observed in EVD survivor eyes (10·8%) cohort compared to close contacts eyes (1·7%, p=0·03). Overall, 47·8% of EVD survivor eyes and 31·9% of close contact eyes presented with an eye disease at the time of our study (p=0·25). Individuals diagnosed with an ocular complication had poorer vision-related quality-of-life (p=0·02). Interpretation: Both health related quality-of-life and vision-related quality-of-life were poor among EVD survivors and close contacts. The high prevalence of eye disease associated with reduced vision health, suggests that cross-disciplinary approaches are needed to address the unmet needs of EVD survivors. Funding: National Institutes of Health R01 EY029594, K23 EY030158; National Eye Institute; Research to Prevent Blindness (Emory Eye Center); Marcus Foundation Combating Childhood Illness; Emory Global Health Institute; Stanley M. Truhlsen Family Foundation.

Uveitis is a common manifestation of post-Ebola syndrome, associated with persistence of Ebola virus (EBOV; Zaire ebolavirus) inside the eye. The iris and retinal pigment epithelia are key components of the blood-ocular barriers, but have the capacity to act as hosts for microorganisms. We investigated the ability of EBOV to productively infect these cell populations. Donor-matched human iris and retinal pigment epithelial isolates (n = 5) were infected with EBOV at a multiplicity of infection of 1 for up to 72 hours. Parallel cultures were infected with Reston virus (RESTV; Reston ebolavirus) or Zika virus (ZIKV), or held uninfected under the same conditions. Viral transcript expression by RT-qPCR on total cellular RNA, cytoimmunofluorescence, and assays of 50% tissue culture infected dose of culture supernatant showed that both iris and retinal pigment epithelial isolates were permissive to infection, and supported replication and release of EBOV, as well as RESTV and ZIKV. However, in comparison to cells isolated from iris, those from retina demonstrated obvious EBOV-induced cytopathic effect, had higher intracellular EBOV nucleoprotein transcript, expressed intracellular EBOV protein more widely, and released EBOV at higher titer. Comparable results were obtained for isolates infected with RESTV and ZIKV. Consistent with observations of retinal pigment epithelial scars in Ebola survivors, our results suggest that an early event in post-Ebola uveitis is infection of the retinal pigment epithelium. Relative susceptibility of retinal pigment epithelial cells to infection with RESTV and ZIKV, as well as EBOV, implies this phenomenon may relate to a cell-specific attribute, such as high phagocytic activity.

Purpose: To describe the devastating ophthalmic sequelae of methamphetamine use disorder in two patients who developed vision loss from ocular complications, including keratitis and endophthalmitis. Observations: Case 1 is a 26-year-old male with hepatitis C, poorly controlled type 1 diabetes, and chronic methamphetamine use who presented with a corneal ulcer in the left eye. Corneal culture grew Staphylococcus aureus and Streptococcus viridans, prompting antibiotic therapy. Follow-up exam showed peripheral corneal ulceration OD and diffusely vascularized and scarred cornea OS, although nonadherence was reported. Vision eventually worsened to hand motions OD and light perception OS.Case 2 is a 44-year-old woman with hepatitis C, acute myeloid leukemia, dry eye syndrome secondary to chronic graft-versus-host disease (GVHD), and chronic methamphetamine use who presented with a diffuse corneal infiltrate and hypopyon. She underwent emergent corneal transplantation, vitrectomy, and broad-spectrum intravitreal and intravenous antibiotics. Vitreous cultures were positive for Streptococcus pyogenes. However, progressive disease eventually required enucleation despite initial globe salvaging measures. Conclusions and importance: These two patient cases highlight the risk of vision loss or blindness due to the detrimental effects of chronic methamphetamine use on the eye, including the potential for keratitis and endophthalmitis. Given the increasing prevalence of methamphetamine use disorder in the United States, further understanding of these toxicities and preventive strategies are needed.

Abstract We report a case of varicella zoster virus (VZV)-associated anterior uveitis in a patient with weight loss, arthritis and signs of inflammatory bowel disease. Her clinical course included the development of a thalamic stroke secondary to VZV cerebral vasculopathy. Following antiviral therapy, the patient’s neurologic symptoms recovered and her ophthalmic findings improved.

Abstract Background The management of an outbreak of endophthalmitis associated with intravitreal bevacizumab represents a challenging real-time process involving identification of cases, treatment and mitigation measures during the outbreak. We summarize the clinical presentation and management of a cluster of endophthalmitis cases from contaminated bevacizumab, in addition to mathematical probabilistic assessment of the number of cases that define an outbreak. Methods A retrospective study was conducted to assess the management of an endophthalmitis outbreak after intravitreal bevacizumab (IVB) administration. Demographic data, clinical information, individual patient management and public health reporting measures were reviewed. Outcomes of patients who received prophylactic antibiotics for endophthalmitis prevention were also reviewed. Binomial tail probability calculations were performed to determine the likelihood of clusters of endophthalmitis that could inform when an outbreak was evolving that would warrant more public health notification measures and communication. Results Forty-five eyes of 42 patients who received IVB from a single batch were reviewed. Four cases of endophthalmitis from Granulicatella adiacens, a nutritionally-variant Streptococcus species, were treated successfully with intravitreal antibiotics ± vitrectomy. Thirty-four of the remaining 41 eyes were treated with prophylactic intravitreal vancomycin with no additional cases of endophthalmitis. Outbreak management also included CDC, ASRS and public health authority notification. Binominal tail probabilities demonstrated the rarity of clusters from a single batch (i.e. ~ 1/10,000 for 2 cases; 1/2 million for 3 cases). However, given the U.S. scale of IVB administration, there is an 87% chance of a cluster ≧ 2 and a 1% chance of a cluster ≧ 3 cases annually, which may guide outbreak management. A process diagram was developed to incorporate patient management and public health measures when an outbreak is suspected. Conclusion Intravitreal antibiotics and vitrectomy were effective in the individual management of cases of endophthalmitis, and no serious adverse events occurred with prophylactic intravitreal vancomycin for at-risk eyes. Best practices for outbreaks should be evaluated, given their likelihood within the U.S. and the sight-threatening consequences of endophthalmitis.

Autoimmune toxicities, while common following treatment with cancer immunotherapies, are not well-characterized in patients treated with BRAF/MEK inhibitors. Emerging data suggest that autoimmune effects may be linked with superior responses to both treatment modalities; however, there is little evidence describing mechanisms of immune-related toxicity for patients on BRAF/MEK inhibitors. Here we describe the experience of a 59-year-old HLA-A2, A29, B27-positive male with recurrent/metastatic melanoma. After progression on checkpoint inhibitor therapy, he was treated with dabrafenib/trametinib followed by encorafenib/binimetinib, which were well-tolerated and resulted in a complete response. Eighteen months into BRAF/MEK inhibitor therapy, and three months after initially finding a complete response, he developed a series of sudden-onset, severe toxicities: namely, bilateral panuveitis, cytopenias, joint pain, skin rash, hypercalcemia, and interstitial nephritis, which led to BRAF/MEKi cessation. Immunological analyses revealed induction of a peripheral type-17 cytokine signature characterized by high IL-23, IL-6, IL-10, IL-17A/F, IL-1β, and IL-21 among other cytokines in plasma corresponding with the height of symptoms. These findings highlight a novel instance of delayed autoimmune-like reaction to BRAF/MEK inhibition and identify a possible role for Th/Tc17 activation in their pathogenesis thus warranting future clinical and immunological characterization.

A 46-year-old patient with previously documented Ebola virus persistence in his ocular fluid, associated with severe panuveitis, developed a visually significant cataract. A multidisciplinary approach was taken to prevent and control infection. Ebola virus persistence was assessed before and during the operation to provide safe, vision-restorative phacoemulsification surgery.

Abstract Background The cases discussed highlight the atypical presentation and diagnostic dilemmas of toxoplasmosis with fulminant retinal necrosis and the potentially devastating visual outcomes of toxoplasma chorioretinitis following local corticosteroid exposure. Case presentation We report a series of three patients who presented with toxoplasmosis mimicking severe acute retinal necrosis. Patients were between 59 and 77 years old and had been exposed to local corticosteroids preceding our evaluation. All patients demonstrated diffuse retinal whitening with severe vision loss on presentation. Polymerase chain reaction testing (PCR) was diagnostic in two patients, and histopathologic examination of a vitrectomy specimen was diagnostic in one patient. All cases of retinitis resolved with anti-parasitic medication; however, visual acuity failed to improve in all patients due to disease severity and presentation. Conclusions Local corticosteroid injection may trigger or exacerbate toxoplasmosis chorioretinitis, leading to fulminant retinal necrosis and severe vision loss. Toxoplasma chorioretinitis should be considered in the differential diagnosis of patients presenting with clinical features of acute retinal necrosis, particularly following local corticosteroid injection regardless of their baseline systemic immune status. Diagnostic vitrectomy may be helpful in patients in whom PCR testing is negative and ocular toxoplasmosis is suspected.

Abstract A 64-year-old man with a past medical history of liver transplantation on chronic immunosuppressive therapy presented with gradual worsening of vision over 2 months in his right eye. His recent history of Aspergillus and Nocardia pneumonia with positive bronchoalveolar lavage, in concert with vitritis and subretinal abscess, were concerning for endogenous endophthalmitis. A sputum culture and transbronchial lung biopsy stains grew Nocardia farcinica although aqueous humor sampling was negative. He was treated with four serial amikacin intravitreal injections over the course of 4 weeks. Pars plana vitrectomy for worsening macular traction and subsequent cataract surgery resulted in significant clinical and anatomic improvement of vision to 20/60 and consolidation of the subretinal abscess.

This report describes the case of a previously healthy 30-year-old woman who presented with uncontrolled hypertension and renal failure. This case emphasizes the importance of considering renal artery disease. The differential diagnosis for renal artery stenosis is discussed, and the diagnosis and management of Takayasu's arteritis in this patient are highlighted. (Level of Difficulty: Beginner.)

PurposeTo assess hospitalized COVID-19 inpatients for the prevalence of retinopathy and tear film SARS-CoV-2 RNA, and associated risk factors for their detection.MethodsHospitalized COVID-19 patients underwent dilated ophthalmic examination and fundus photography. Conjunctival swabs were assessed for SARS-CoV-2 RT-PCR via a triple target assay. We assessed the relationships of retinopathy with clinical outcomes, systemic risk factors and laboratory data.ResultsThe median age was 59.5 years and 29 (48%) were female. Retinopathy associated with COVID-19 was observed in 12 of 60 patients (20%). The median age of patients with COVID-19 retinopathy was 51.5 compared to 62.5 years in individuals without retinopathy (p = 0.01). Median BMI was 34.3 in patients with retinopathy versus 30.9 in those without retinopathy (p = 0.04). Fifteen of 60 patients (25%) tested SARS-CoV-2 RNA-positive in their tear film without a relationship with timing of illness and hospitalization. The N2 gene was particularly sensitive with 18 of 19 eyes (94.7%) showing N2-positivity, including 2 patients with alpha variant-positivity (B.1.1.7).ConclusionRetinopathy was observed in 20% of patients hospitalized for COVID-19. Patients with retinopathy were more likely to be younger and have higher BMI than hospitalized patients without retinopathy. Tear film SARS-CoV-2 RNA was detected in 25% of patients. The relationship of obesity and age with retinopathy requires further investigation.

Amidst the ongoing monkeypox outbreak, global awareness has been directed towards the prevention of viral transmission and case management, with the World Health Organization declaring the outbreak a public health emergency of international concern. Monkeypox virus is one of several species in the Orthopoxvirus genus, with other species of the genus including the variola, cowpox, mousepox, camelpox, raccoonpox, skunkpox, and volepox viruses. Although the nomenclature of these species is based on the animal host from which they were originally isolated, transmission from animals to humans has been reported with several species. The progression of disease, following an incubation period, typically consists of a prodromal phase with systemic flu-like symptoms. Various organ systems may be affected in addition to the formation of pathognomonic skin lesions. As monkeypox poses a continued public health concern, the ophthalmic sequelae of monkeypox virus, especially those leading to vision loss, warrant consideration as well. This review provides a comprehensive summary of the ophthalmic implications of poxviruses in clinical and laboratory settings reported in the literature, as well as areas of unmet need and future research.

Abstract Background JIA-associated uveitis (JIAU) is a serious, sight-threatening disease with significant long-term complications and risk of blindness, even with improved contemporary treatments. The MIWGUC was set up in order to propose specific JIAU activity and response items and to validate their applicability for clinical outcome studies. Methods The group consists of 8 paediatric rheumatologists and 7 ophthalmologists. A consensus meeting took place on November 2015 in Barcelona (Spain) with the objective of validating the previously proposed measures. The validation process was based on the results of a prospective open, international, multi-centre, cohort study designed to validate the outcome measures proposed by the initial MIWGUC group meeting in 2012. The meeting used the same Delphi and nominal group technique as previously described in the first paper from the MIWGUC group (Arthritis Care Res 64:1365–72, 2012). Patients were included with a diagnosis of JIA, aged less than 18 years, and with active uveitis or an uveitis flare which required treatment with a disease-modifying anti-rheumatic drug. The proposed outcome measures for uveitis were collected by an ophthalmologist and for arthritis by a paediatric rheumatologist. Patient reported outcome measures were also measured. Results A total of 82 patients were enrolled into the validation cohort. Fifty four percent (n = 44) had persistent oligoarthritis followed by rheumatoid factor negative polyarthritis (n = 15, 18%). The mean uveitis disease duration was 3.3 years (SD 3.0). Bilateral eye involvement was reported in 65 (79.3%) patients. The main findings are that the most significant changes, from baseline to 6 months, are found in the AC activity measures of cells and flare. These measures correlate with the presence of pre-existing structural complications and this has implications for the reporting of trials using a single measure as a primary outcome. We also found that visual analogue scales of disease activity showed significant change when reported by the ophthalmologist, rheumatologist and families. The measures formed three relatively distinct groups. The first group of measures comprised uveitis activity, ocular damage and the ophthalmologists’ VAS. The second comprised patient reported outcomes including disruption to school attendance. The third group consisted of the rheumatologists’ VAS and the joint score. Conclusions We propose distinctive and clinically significant measures of disease activity, severity and damage for JIAU. This effort is the initial step for developing a comprehensive outcome measures for JIAU, which incorporates the perspectives of rheumatologists, ophthalmologists, patients and families.

BackgroundFollowing the West African Ebola virus disease (EVD) outbreak of 2013-2016 and more recent EVD outbreaks in the Democratic Republic of Congo, thousands of EVD survivors are at-risk for sequelae including uveitis, which can lead to unremitting inflammation and vision loss from cataract. Because of the known risk of Ebola virus persistence in ocular fluid and the need to provide vision-restorative, safe cataract surgery, the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study was implemented in Sierra Leone. During implementation of this multi-national study, challenges included regulatory approvals, mobilization, community engagement, infection prevention and control, and collaboration between multiple disciplines. In this report, we address the multifacted approach to address these challenges and the impact of implementation science research to address an urgent clinical subspecialty need in an outbreak setting.Methodology/principal findingsGiven the patient care need to develop a protocol to evaluate ocular fluid for Ebola virus RNA persistence prior to cataract surgery, as well as protocols to provide reassurance to ophthalmologists caring for EVD survivors with cataracts, the EVICT study was designed and implemented through the work of the Ministry of Health, Sierra Leone National Eye Programme, and international partnerships. The EVICT study showed that all 50 patients who underwent ocular fluid sampling at 19 and 34 months, respectively, tested negative for Ebola virus RNA. Thirty-four patients underwent successful cataract surgery with visual acuity improvement. Here we describe the methodology for study implementation, challenges encountered, and key issues that impacted EVD vision care in the immediate aftermath of the EVD outbreak. Key aspects of the EVICT study included defining the pertinent questions and clinical need, partnership alignment with key stakeholders, community engagement with EVD survivor associations, in-country and international regulatory approvals, study site design for infection prevention and control, and thorough plans for EVD survivor follow-up care and monitoring. Challenges encountered included patient mobilization owing to transportation routes and distance of patients in rural districts. Strong in-country partnerships and multiple international organizations overcame these challenges so that lessons learned could be applied for future EVD outbreaks in West and Central Africa including EVD outbreaks that are ongoing in Guinea and Democratic Republic of Congo.Conclusions/significanceThe EVICT Study showed that cataract surgery with a protocol-driven approach was safe and vision-restorative for EVD survivors, which provided guidance for EVD ophthalmic surgical care. Ophthalmologic care remains a key aspect of the public health response for EVD outbreaks but requires a meticulous, yet partnered approach with international and local in-country partners. Future efforts may build on this framework for clinical care and to improve our understanding of ophthalmic sequelae, develop treatment paradigms for EVD survivors, and strengthen vision health systems in resource-limited settings.

PURPOSE:To describe epidemiologic features of patients with presumed ocular histoplasmosis syndrome (POHS) in the United States using insurance claims data and compare POHS patients with and without choroidal neovascularization (CNV). DESIGN:Retrospective cohort study. METHODS:Patients with International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for histoplasmosis retinitis on an outpatient claim in the 2014 IBM® MarketScan® Commercial Database and the Medicare Supplemental Database who were enrolled for at least 2 years after the POHS code. MAIN OUTCOME MEASURES:Data related to testing, treatment, and direct medical costs. RESULTS:Among >50 million total MarketScan enrollees, 6,678 (13 per 100,000) had a POHS diagnosis code. Of those, 2,718 were enrolled for 2 years; 698 (25%) of whom had a CNV code. Eleven of the 13 states with the highest POHS rates bordered the Mississippi and Ohio rivers. CNV patients had significantly more eye care provider visits (mean 8.8 vs. 3.2, p

The purpose of this study was to describe the ocular findings, structural ocular complications, and vision impairment in a cohort of Lassa fever survivors in Kenema, Sierra Leone. A retrospective, uncontrolled, cross-sectional study of 31 Lassa fever survivors (62 eyes) who underwent an ophthalmic evaluation in January 2018 at the Kenema Government Hospital in Kenema, Sierra Leone was performed. Data collection included demographic information, ocular/systemic symptoms, visual acuity (VA), and ophthalmic examination findings. Main outcome measures included anterior and posterior segment ophthalmic manifestations and level of VA impairment in Lassa fever survivors. Anterior segment findings included cataract (18%) and pterygium (2%), while posterior segment manifestations consisted of glaucoma (6%), preretinal hemorrhage (2%), and lattice degeneration (2%). Findings suggestive of prior sequelae of uveitis included chorioretinal scarring (5%), retinal fibrosis (3%), and vitreous opacity (2%). Visual acuity was normal/mildly impaired in 53 eyes (85%), moderately impaired in 6 eyes (10%), and 3 eyes (5%) were considered blind by the World Health Organization (WHO) criteria. Median VA was worse in Lassa fever survivors with ophthalmic disease findings (p

The purpose of this study was to evaluate potential insights into the pathogenesis of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) using multimodal diagnostic imaging and laboratory evaluation in long-term follow-up. A retrospective, single-center case series was conducted on seven consecutive patients (14 eyes) who were given a diagnosis of APMPPE from March 1, 2011, through June 30, 2019 with at least three months of follow-up. Clinical characteristics (age, symptoms, visual acuity [VA]), laboratory testing including coxsackievirus titers, and multimodal imaging from fundus photography, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICG) were analyzed for each patient. The initial median VA was 20/71 and final median VA was 20/22. Coxsackievirus B (CVB) titers were elevated (≥ 1:80) in six of seven patients, with a four-fold increase in convalescent titers seen in two patients suggestive of recent infection. All patients were treated with oral corticosteroids, and five patients underwent corticosteroid-sparing immunomodulatory therapy. Initially, multifocal deep choroidal lesions were observed in the posterior pole corresponding to patches of hypocyanescence on ICG. Overlying retinal pigment epithelium (RPE) disease was observed on FAF, although this finding was not universally observed, suggesting that RPE disease may occur as a sequelae to unchecked choroidal inflammation. SD-OCT architectural changes confirmed outer retina and ellipsoid zone disruption. FA of active lesions showed early hypofluorescence and late hyperfluorescence with surrounding leakage while inactive disease showed areas of staining. Long-term follow-up of multimodal diagnostic imaging in APMPPE revealed that choroidal inflammation likely precedes RPE change and photoreceptor damage. Elevation of coxsackievirus titers with seroconversion may be associated with an infectious trigger in concert with immune-mediated disease in this posterior uveitis syndrome.

Abstract Background Biomarkers in easily obtained specimens that accurately predict uveitis in children with juvenile idiopathic arthritis (JIA) are needed. Aqueous humor has been studied for biomarkers, but is not routinely available. We evaluated tears from children with chronic anterior uveitis (CAU) for biomarkers reported in aqueous humor. In this pilot study, we used Schirmer strips to collect tears from seven children (nine eyes); three children had JIA- associated uveitis (JIA-U) and four had idiopathic disease (I-CAU). Liquid chromatography-tandem mass spectrometry was used to identify and quantify tear proteins. The Mann-Whitney U test identified differential tear protein expression between children with JIA-U and those with I-CAU. Results S100A9, LAP3, TTR, MIF, sCD14, S100A8, and SAA1 were detected in tears of all children; the same cytokines have been reported in aqueous humor of children with JIA-U. Tears from children with JIA-U had higher expression of proteins associated with inflammatory arthritis (SEMA3G, TIMP1, HEXB, ERN1, and SAA1) than tears from those with I-CAU. In addition, we found higher expression of sCD14, S100A8, and SAA1, but lower expression of S100A9, LAP3, TTR, and MIF, in tears from children with JIA-U compared to tears from those with I-CAU. Conclusions Tears contain similar cytokine profiles to aqueous humor in children with CAU and may be a clinically useful source of disease biomarkers. Tears from children with JIA-U also contain cytokines associated with inflammatory arthritis; furthermore, differential expression of other tear proteins as well may provide clues to intrinsic differences between JIA-U and I-CAU, despite their similar clinical phenotypes.

Background: Ebola virus disease (EVD) survivors are at risk for uveitis during convalescence. Vision loss has been observed following uveitis due to cataracts. Since Ebola virus (EBOV) may persist in the ocular fluid of EVD survivors for an unknown duration, there are questions about the safety and feasibility of vision restorative cataract surgery in EVD survivors. Methods: We conducted a cross-sectional study of EVD survivors anticipating cataract surgery and patients with active uveitis to evaluate EBOV RNA persistence in ocular fluid, as well as vision outcomes post cataract surgery. Patients with aqueous humor that tested negative for EBOV RNA were eligible to proceed with manual small incision cataract surgery (MSICS). Findings: We screened 137 EVD survivors from June 2016 – August 2017 for enrolment. We enrolled 50 EVD survivors; 46 with visually significant cataract, 1 with a subluxated lens, 2 with active uveitis and 1 with a blind painful eye due to uveitis. The median age was 24.0 years (IQR 17–35) and 35 patients (70%) were female. The median logMAR visual acuity (VA) was 3.0 (Snellen VA Hand motions; Interquartile Range, IQR: 1.2-3.0, Snellen VA 20/320 – Hand motions). All patients tested negative for EBOV RNA by RT-PCR in aqueous humor/vitreous fluid and conjunctiva at a median of 19 months (IQR 18-20) from EVD diagnosis in Phase 1 of ocular fluid sampling and 34 months (IQR 32-36) from EVD diagnosis in Phase 2 of ocular fluid sampling. Thirty-four patients underwent MSICS, with a preoperative median VA improvement from hand motions to 20/30 at three-month postoperative follow-up (P

Uveitis refers to a broad group of inflammatory disorders of the eye that often require medical and surgical management to improve or stabilize vision and prevent vision-threatening pathological changes to the eye. Drug delivery to the eye to combat inflammation and subsequent complications from uveitic conditions is complex as there are multiple barriers to absorption limiting availability of the needed drug in the affected tissues. As such, there has been substantial interest in developing new drugs and drug delivery platforms to help reduce intraocular inflammation and its complications. In this review, we discuss the challenges of drug delivery, novel technologies recently approved for uveitis patient care and promising drug delivery platforms for uveitis and sequelae of ocular inflammation.

Following publication of the original article [1], we have been notified that the author Joan Calzada should not have been included to the team of authors. The authors’ team, thus, should be as follows:

BACKGROUND:In the wake of the West African Ebola virus disease (EVD) outbreak of 2014-2016, thousands of EVD survivors began to manifest a constellation of systemic and ophthalmic sequelae. Besides systemic arthralgias, myalgias, and abdominal pain, patients were developing uveitis, a spectrum of inflammatory eye disease leading to eye pain, redness, and vision loss. To investigate this emerging eye disease, resources and equipment were needed to promptly evaluate this sight-threatening condition, particularly given our identification of Ebola virus in the ocular fluid of an EVD survivor during disease convalescence. METHODOLOGY/PRINCIPAL FINDINGS:A collaborative effort involving ophthalmologists, infectious disease specialists, eye care nurses, and physician leadership at Eternal Love Winning Africa (ELWA) Hospital in Liberia led to the development of a unique screening eye clinic for EVD survivors to screen, treat, and refer patients for more definitive care. Medications, resources, and equipment were procured from a variety of sources including discount websites, donations, purchasing with humanitarian discounts, and limited retail to develop a screening eye clinic and rapidly perform detailed ophthalmologic exams. Findings were documented in 96 EVD survivors to inform public health officials and eye care providers of the emerging disease process. Personal protective equipment was tailored to the environment and implications of EBOV persistence within intraocular fluid. CONCLUSIONS/SIGNIFICANCE:A screening eye clinic was feasible and effective for the rapid screening, care, and referral of EVD survivors with uveitis and retinal disease. Patients were screened promptly for an initial assessment of the disease process, which has informed other efforts within West Africa related to immediate patient care needs and our collective understanding of EVD sequelae. Further attention is needed to understand the pathogensis and treatment of ophthalmic sequelae given recent EVD outbreaks in West Africa and ongoing outbreak within Democratic Republic of Congo.

Recent Ebola epidemics, the ongoing COVID-19 pandemic, and emerging infectious disease threats have highlighted the importance of global infectious diseases and responses to public health emergencies. Ophthalmologists are essential health care workers who provide urgent and emergent vision care services during outbreaks and address the ocular consequences of epidemic and pandemic infectious diseases. In 2017, the World Health Organization (WHO) identified high priority pathogens likely to cause a future epidemic with the goal of guiding research and development to improve diagnostic tests, vaccines, and medicines. These measures were necessary to better inform and respond to public health emergencies. Given the ocular complications associated with emerging infectious diseases, there is a need to recognize the ophthalmic sequelae for future vision health preparedness for potential future outbreaks. The WHO High Priority pathogens list provides a roadmap for ophthalmologists and subspecialty providers that will guide strategic areas of research for clinical care and preparedness for future pandemic threats. This review summarizes these key viral pathogens, summarizes major systemic disease findings, and delineates relevant ocular complications of the WHO High Priority pathogens list, including Crimean-Congo hemorrhagic fever, Filovirus diseases (Ebola virus disease and Marburg hemorrhagic fever), human Coronaviruses, Lassa Fever, Nipah virus infection, Zika, and Rift Valley fever.

Ebola virus disease (EVD) and emerging infectious disease threats continue to threaten life, prosperity and global health security. To properly counteract EVD, an improved understanding of the long-term impact of recent EVD outbreaks in West Africa and the Democratic Republic of Congo are needed. In the wake of recent outbreaks, numerous health sequelae were identified in EVD survivors. These findings include joint pains, headaches, myalgias, and uveitis, a vision-threatening inflammatory condition of the eye. Retrospective and more recent prospective studies of EVD survivors from West Africa have demonstrated that uveitis may occur in 13–34% of patients with an increase in prevalence from baseline to 12-month follow-up. The clinical spectrum of disease ranges from mild, anterior uveitis to severe, sight-threatening panuveitis. Untreated inflammation may ultimately lead to secondary complications of cataract and posterior synechiae, with resultant vision impairment. The identification of Ebola virus persistence in immune privileged organs, such as the eye, with subsequent tissue inflammation and edema may lead to vision loss. Non-human primate models of EVD have demonstrated tissue localization to the eye including macrophage reservoirs within the vitreous matter. Moreover, in vitro models of Ebola virus have shown permissiveness in retinal pigment epithelial cells, potentially contributing to viral persistence. Broad perspectives from epidemiologic studies of the outbreak, animal modeling, and immunologic studies of EVD survivors have demonstrated the spectrum of the eye disease, tissue specificity of Ebola virus infection, and antigen-specific immunologic response. Further studies in these areas will elucidate the mechanisms of this highly prevalent disease with the potential for improved therapeutics for Ebola virus in immune-privileged sites.

Brian T Chan-Kai1, Steven Yeh2, Richard G Weleber2, Peter J Francis2, Grazyna Adamus2, S Robert Witherspoon3, Andreas K Lauer11Cullen Eye Institute, Baylor College of Medicine, Houston, Texas; 2Casey Eye Institute, Oregon Health and Science University, Portland, Oregon; 3Retina Institute of Texas, Dallas, Texas, USAAim: Transplant chorioretinopathy is a rare complication following solid organ or bone ­marrow transplantation and can result in severe vision loss. This series presents electroretinogram (ERG) results in patients with this condition.Methods: Patients who presented with bilateral vision loss following bone marrow or solid organ transplantation were identified. A complete ophthalmologic examination, fundus ­photography, and fluorescein angiography (FA) were performed. Full-field ERG was obtained in all patients and a multifocal ERG (mfERG) was obtained in two patients.Results: Four patients were identified. All patients had bilateral vision loss and displayed a characteristic pattern of mottled hyperfluorescence on FA. Three patients developed ­progressive vision loss ranging from 20/60 to hand motions whereas one retained 20/40 vision. All patients exhibited moderate to severe cone dysfunction, while the degree of rod abnormalities was varied. Two patients with severe cone dysfunction showed mild clinical changes initially, but later developed progressive vision loss and chorioretinal atrophy.Conclusion: Transplant chorioretinopathy patients undergoing ERG testing show cone ­dysfunction with a variable degree of rod dysfunction. ERG abnormalities preceded the visual acuity and clinical changes in two patients, suggesting that ERG may be a helpful predictor of the clinical course in this rare disease.Keywords: transplant, chorioretinopathy, electroretinogram, ERG, mfERG

CAPN5 mutations have been linked to autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), a blinding autoimmune eye disease. Here, we link a new CAPN5 mutation to ADNIV and model the three-dimensional structure of the resulting mutant protein. In our study, a kindred with inflammatory vitreoretinopathy was evaluated by clinical eye examinations, DNA sequencing, and protein structural modeling to investigate the disease-causing mutation. Two daughters of an affected mother demonstrated symptoms of stage III ADNIV, with posterior uveitis, cystoid macular edema, intraocular fibrosis, retinal neovascularization, retinal degeneration, and cataract. The women also harbored a novel guanine to thymine (c.750G>T, p.Lys250Asn) missense mutation in exon 6 of CAPN5, a gene that encodes a calcium-activated cysteine protease, calpain-5. Modeling based on the structures of all known calpains revealed the mutation falls within a calcium-sensitive flexible gating loop that controls access to the catalytic groove. Three-dimensional modeling placed the new mutation in a region adjacent to two previously identified disease-causing mutations, all three of which likely disrupt hydrogen bonding within the gating loop, yielding a CAPN5 with altered enzymatic activity. This is the third case of a CAPN5 mutation leading to inherited uveitis and neovascular vitreoretinopathy, suggesting patients with ADNIV features should be tested for CAPN5 mutations. Structural modeling of novel variants can be used to support mechanistic consequences of the disease-causing variants.

About one-third of patients suffering from systemic lupus erythematosus have ocular manifestations. The most common manifestation is keratoconjunctivitis sicca. The most vision threatening are retinal vasculitis and optic neuritis/neuropathy. Prompt diagnosis and treatment of eye disease is paramount as they are often associated with high levels of systemic inflammation and end-organ damage. Initial management with high-dose oral or IV corticosteroids is often necessary. Multiple “steroid-sparing” treatment options exist with the most recently studied being biologic agents.