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Background This post hoc analysis compared the efficacy and safety of CLS-TA to other commonly available treatments for noninfectious uveitis (NIU). Methods Results from the PEACHTREE study were compared between subjects randomized to CLS-TA not requiring rescue therapy and those subjects randomized to control and subsequently requiring rescue therapy. Endpoints included best corrected visual acuity (BCVA), central subfield thickness (CST), treatment emergent adverse events (TEAEs), and intraocular pressure (IOP) related safety findings. Results In this analysis, there were 83 unrescued CLS-TA subjects and 46 rescued control subjects. At Week 24, 51.9% of the unrescued CLS-TA subjects gained ≥15 letters in BCVA, compared to 37.0% of the rescued control subjects (P = 0.115). Unrescued CLS-TA subjects showed a mean gain of 15.7 versus 10.9 letters in rescued control subjects (P = 0.080). A significantly greater mean reduction in CST was observed for unrescued CLS-TA subjects versus rescued control subjects (174.0 and 148.5 μm; P = 0.040). Of unrescued CLS-TA subjects, 4.9% experienced IOP elevations ≥ 30 mm Hg at any visit versus 10.9% of rescued control subjects. Further, use of IOP-lowering medications appeared lower in unrescued CLS-TA subjects versus rescued control subjects (7.2% versus 13.0%). There were no IOP-related surgical interventions in either group. Conclusion CLS-TA subjects experienced significantly greater reduction in CST and tended towards greater improvement in BCVA, compared with rescued control subjects. Suprachoroidally administered CLS-TA showed a lower incidence of IOP-related safety findings. This article is protected by copyright. All rights reserved.

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.

Purpose The mainstay empiric treatments of bacterial endophthalmitis are intravitreal vancomycin and ceftazidime. In the United States, up to 10% of the general population has a reported penicillin (PCN) allergy. Despite low cross-reactivity between PCN and later-generation cephalosporins, some providers alter the intravitreal antibiotic choice for endophthalmitis because of concern for allergic reactions. We evaluated the management strategies of infectious endophthalmitis in the setting of self-reported systemic antibiotic allergies and the association with adverse reactions after standard intravitreal antibiotic administration. Design Single-center, retrospective cohort study. Participants All patients with endophthalmitis between 2005 and 2019 and documented PCN, PCN-analog, cephalosporin, or vancomycin allergy who received intravitreal antibiotics on the basis of International Classification of Diseases 9th and 10th Revisions, and Current Procedural Terminology codes. Methods Retrospective chart review. Main Outcome Measures Any allergic reaction after intravitreal injection, additional surgical interventions required for treatment, and visual function at last recorded visit. Results Of the 65 patients included in this cohort, the most common causes of endophthalmitis were postcataract extraction surgery (n = 23, 35.4%) and postintravitreal injection (n = 11, 16.9%). All patients (65/65) received intravitreal vancomycin, and 81.5% (53/65) received intravitreal ceftazidime. Of the 53 patients who received intravitreal ceftazidime, 46 (86.8%) had allergies to PCNs alone, 5 (9.4%) had a cephalosporin allergy alone, and 2 (3.8%) had reported allergies to both PCN and cephalosporin antibiotics. Two patients (3.1%) with a documented vancomycin allergy received intravitreal vancomycin without complication. No patients exhibited any systemic or local allergic reactions or complications after intravitreal injection. Conclusions There were no documented allergic reactions in this cohort of patients with systemic antibiotic allergies who were treated for infectious endophthalmitis. Our findings are consistent with previous reports of a low allergic cross-reactivity between PCN and later-generation cephalosporins. Ophthalmologists should use evidence-based practices and a careful informed consent process when choosing intravitreal antibiotics for patients with specific antibiotic allergies. In the routine patient with suspected bacterial endophthalmitis, PCN allergy may not be an absolute contraindication to intravitreal cephalosporin use.

To evaluate changes in health-related and vision-related quality of life (VRQoL) among patients with noninfectious uveitis who were treated with antimetabolites.Secondary analysis of a randomized controlled trial.Patients with noninfectious uveitis from India, the United States, Australia, Saudi Arabia, and Mexico.From 2013 through 2017, 216 participants were randomized to receive 25 mg weekly oral methotrexate or 1.5 g twice daily oral mycophenolate mofetil. Median changes in quality of life (QoL) were measured using Wilcoxon signed-rank tests, and differences between treatment groups were measured using linear mixed models, adjusting for baseline QoL score, age, gender, and site. Among Indian patients, VRQoL scores from a general scale (the National Eye Institute Visual Function Questionnaire [NEI-VFQ]) and a culturally specific scale (the Indian Visual Function Questionnaire [IND-VFQ]) were compared using Pearson correlation tests.Vision-related QoL (NEI-VFQ and IND-VFQ) and health-related QoL (HRQoL; physical component score [PCS] and mental component score [MCS] of the Medical Outcomes Study 36-Item Short Form Survey [SF-36v2]) were measured at baseline, the primary end point (6 months or treatment failure before 6 months), and the secondary end point (12 months or treatment failure between 6 and 12 months).Among 193 participants who reached the primary end point, VRQoL increased from baseline by a median of 12.0 points (interquartile range [IQR], 1.0-26.1, NEI-VFQ scale), physical HRQoL increased by a median of 3.6 points (IQR, -1.4 to 14.9, PCS SF-36v2), and mental HRQoL increased by a median of 3.0 points (IQR, -3.7 to 11.9, MCS SF-36v2). These improvements in NEI-VFQ, SF-36v2 PCS, and SF-36v2 MCS scores all were significant (P0.01). The linear mixed models showed that QoL did not differ between treatment groups for each QoL assessment (NEI-VFQ, IND-VFQ, PCS SF-36v2, and MCS SF-36v2; P0.05 for all). The NEI-VFQ and IND-VFQ scores for Indian participants were correlated highly at baseline and the primary and secondary end points (correlation coefficients, 0.87, 0.80, and 0.90, respectively).Among patients treated with methotrexate or mycophenolate mofetil for uveitis, VRQoL and HRQoL improved significantly over the course of 1 year and did not differ by treatment allocation. These findings suggest that antimetabolites could improve overall patient well-being and daily functioning.

Purpose To determine classification criteria for Behcet disease uveitis. Design Machine learning of cases with Behcet disease and 5 other panuveitides. Methods Cases of panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation set. Results One thousand twelve of cases panuveitides, including 194 cases of Behcet disease with uveitis, were evaluated by machine learning. The overall accuracy for panuveitides was 96.3% in the training set and 94.0% in the validation set (95% confidence interval 89.0, 96.8). Key criteria for Behcet disease uveitis were a diagnosis of Behcet disease using the International Study Group for Behcet Disease criteria and a compatible uveitis, including: 1) anterior uveitis; 2) anterior chamber and vitreous inflammation; 3) posterior uveitis with retinal vasculitis and/or focal infiltrates; or 4) panuveitis with retinal vasculitis and/or focal infiltrates. The misclassification rates for Behcet disease uveitis were 0.6 % in the training set and 0% in the validation set, respectively. Conclusions The criteria for Behcet disease uveitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

To report the cytopathology of vitreous biopsy samples in patients with acute retinal necrosis (ARN) who underwent pars plana vitrectomy (PPV). We also describe two patients with unique clinical courses, cytopathologic findings, and immune response.A retrospective review of patients with ARN who developed retinal detachment (RD) and underwent PPV from 22011 to 2019 at the Emory Eye Center was performed to assess cytopathology findings of vitreous biopsy samples. Patient demographics and laboratory testing including aqueous humor PCR for viral pathogens were recorded. Additional clinical details abstracted included intravitreal injections, surgical procedures, and vitreous cytopathological reports including immunohistochemistry findings.Fourteen eyes of 12 patients with RD were reviewed. Ten eyes showed HSV DNA (71%) and 4 demonstrated VZV DNA (29%). All eyes received intravitreal antivirals (i.e. ganciclovir or foscarnet) with a median of 8.5 intravitreal injections per eye. Diagnoses prompting PPV included tractional RD in 14 eyes (100%), rhegmatogenous RD in 8 eyes (57%), vitreous hemorrhage in 4 eyes (29%) and vitreous opacity in 4 (29%). Ophthalmic pathology reports showed lymphocyte populations in 10 eyes (71%) with a CD3 + T-cell predominance in two patients where immunohistochemistry of CD3+ and CD20+ for T- and B-cell populations was performed. Observed immune cell populations included macrophages or histiocytes (11 eyes, 79%) and polymorphonuclear cells in 4 eyes (29%). Initial median VA was 2.5 (IQR 2.0-3.0) and improved to 2.0 (IQR 1.48-3.00,Our cohort of ARN patients undergoing PPV show a spectrum of immunologic findings with the majority demonstrating a lymphocytic response. Histiocytes, macrophages, and PMNs were also observed. Cytopathologic and immunologic studies suggest that both innate and adaptive immunity are responsible for the clinical disease findings observed in ARN. The variability of the response to treatment in patients with ARN may reflect patient-to-patient differences in their antigen-specific immune response. Understanding the immunologic response associated with ARN may provide valuable information regarding the dosing and timing of treatment.

Purpose: To present a patient with Rosai-Dorfman Disease (RDD), a histiocytic proliferative disorder typified by lymphadenopathy with rare ocular manifestations, who developed panuveitis that responded to pegylated interferon.Methods: Descriptive case report of a patient with RDD with multi-organ involvement including ocular manifestations including bilateral panuveitis with choroidal masses.Results: A 54-year-old African American woman with known systemic RDD of the breast, lung, and gastrointestinal tract presented with panuveitis with choroidal masses in both eyes. Her systemic and ocular disease initially responded well to oral and topical steroid therapy. Later, however, her systemic disease progressed with multiple muscular and bony lesions. Systemic therapy was switched to pegylated interferon, a cytokine with antiviral, antitumor and immunomodulatory activity. After 14 months of therapy with pegylated interferon, the patient's systemic and ocular disease stabilized.Conclusion: Rosai-Dorfman disease may be complicated by panuveitis and choroidal masses that may respond to pegylated interferon with stabilization of systemic and ocular manifestations. A multi-disciplinary approach is essential given the unique diagnostic and management challenges of RDD.

Purpose Determine the efficacy of combination intravitreal and systemic antiviral therapy for the treatment of acute retinal necrosis (ARN) and risk factors impacting visual acuity (VA) and retinal detachment (RD) outcomes. Design Single-center retrospective case series. Participants Patients with an ARN diagnosis based on clinical features and polymerase chain reaction confirmation who were treated at a tertiary referral, university-based academic practice. Methods Patient records were reviewed for demographic information including age and gender. Snellen VA, disease findings including RD outcomes, optic nerve involvement, and treatments were recorded. Incidence rates of major VA and RD outcomes were calculated based on the number of events and exposure times. Cox proportional hazards regression modeling and survival analyses were used to identify factors related to VA and RD outcomes over time. Main Outcome Measures Logarithm of the minimal angle of resolution VA, 2-line or more VA gain, severe vision loss (SVL) of 20/200 or worse, RD development, and fellow eye involvement. Results Twenty-three eyes of 21 patients (11 male, 10 female) were reviewed. Thirteen patients (62%) had herpes simplex virus and 8 patients (38%) had varicella zoster virus. The event rate for 2-line or more VA gain was 0.49 events/eye-year (95% confidence interval [CI], 0.26–0.86 events/eye-year), whereas the rate of SVL was 0.61 events/eye-year (95% CI, 0.34–1.02 events/eye-year). Retinal detachment development was observed at a rate of 0.59 events/eye-year (95% CI, 0.33–1.00 events/eye-year). Thirteen of 23 eyes (57%) demonstrated RD with a mean time of 120 days after ARN diagnosis. With each additional quadrant of retina involved, a greater risk of RD development over time was observed (hazard ratio, 2.21; 95% CI, 1.12–4.35). Nine percent of eyes progressed with additional quadrantic involvement, despite combination systemic and intravitreal antiviral therapy; however, none of the 19 patients demonstrating unilateral ARN showed fellow-eye involvement after initiation of therapy. Conclusions Combination intravitreal and systemic antiviral therapy for ARN can be effective in improving VA and limiting retinitis progression. Each additional quadrant of retina involved was associated with a 2.2-fold greater risk of RD, which may impact monitoring, timing of intervention, and patient counseling.

PurposeTo evaluate local and systemic safety of suprachoroidal (SC) triamcinolone acetonide injectable suspension (CLS-TA) injections in subjects with non-infectious uveitis (NIU).DesignOpen-label, prospective multicentre safety study.ParticipantsThirty-eight subjects with NIU, with and without macular oedema (MO).MethodsTreatment consisted of two suprachoroidal injections of CLS-TA 4 mg, 12 weeks apart. Best-corrected visual acuity (BCVA), adverse event (AE) assessment, ophthalmic examinations and optical coherence tomography (OCT) were conducted every 4 weeks for 24 weeks. Blood samples were analysed for plasma triamcinolone acetonide (TA) concentrations.Main outcome measuresThe main outcome measure was frequency of AEs. Other endpoints included plasma TA concentrations, change in signs of inflammation, BCVA and retinal central subfield thickness (CST).ResultsBased on a CST of >300 µm, 20 out of 38 subjects had MO at baseline. Mean intraocular pressure (IOP) was 13.3 mm Hg at baseline and 15.2 mm Hg at week 24 in the study eye. A total of six (15.8%) subjects had an IOP rise >10 mm Hg compared with baseline, in the study eye, and two (5.3%) subjects had IOP >30 mm Hg (maximum 34 mm Hg at week 8 and 38 mm Hg at week 20). Cataract formation AEs were reported in four study eyes; one of which was deemed treatment-related. No serious ocular AEs in the study eye occurred in the study. Quantifiable post-injection TA plasma concentration was ConclusionsSuprachoroidally administered CLS-TA was safe and well tolerated over the 24-week, open-label study in NIU subjects with and without MO.

PURPOSE: To present a case of refractory systemic lupus erythematosus (SLE)-associated retinal vasculitis that responded to the anti-tumor necrosis factor (TNF)-alpha inhibitor adalimumab as corticosteroid-sparing therapy. METHODS: Descriptive case report of a patient with SLE with retinal vasculitis complicated by an ischemic retinal vein occlusion and cystoid macular edema. RESULTS: A 30-year-old female patient with a history of SLE presented with retinal vasculitis and an ischemic, branch retinal vein occlusion with macular edema in the left eye. Oral corticosteroid was administered along with mycophenolate mofetil (MMF) as a corticosteroid-sparing agent. Despite MMF therapy, the patient developed an exacerbation of her vasculitis with involvement of both eyes. Adalimumab was initiated with resultant resolution of retinal vasculitis as a corticosteroid-sparing strategy with over 2-years of follow-up. CONCLUSION: Anti-TNF-alpha therapy with adalimumab may be effective as a corticosteroid-sparing agent in select patients with ocular inflammation associated with SLE.

Purpose: The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has escalated rapidly since December 2019. Understanding the ophthalmic manifestations in patients and animal models of the novel coronavirus may have implications for disease surveillance. Recognition of the potential for viral transmission through tear film has ramifications for patients, physicians, and the public. Methods: Information from relevant published journal articles was surveyed using a computerized PubMed search and public health websites. We summarize knowledge of ophthalmic manifestations of SARS-CoV-2 infection in patients and animal models, risk-mitigation measures for patients and providers, and implications for retina specialists. Results: SARS-CoV-2 is efficiently transmitted among humans, and although the clinical course is mild in most infected patients, severe complications including pneumonia, acute respiratory distress syndrome, and death can ensue, most often in elderly patients and individuals with comorbidities. Conjunctivitis occurs in a minority of patients with COVID-19, and SARS-CoV-2 RNA has been identified primarily with conjunctivitis. Uveitis has been observed in animal models of coronavirus infection, and cotton-wool spots have been reported recently. Conclusions: SARS-CoV-2 and other coronaviruses have been rarely associated with conjunctivitis. Identification of SARS-CoV and SARS-CoV-2 RNA in the tear film of patients and its highly efficient transmission via respiratory aerosols supports eye protection, mask, and gloves as part of infection prevention and control recommendations for retina specialists. Disease surveillance during the COVID-19 pandemic may also include ongoing evaluation for uveitis and retinal disease given prior findings from animal models and a recent report of retinal manifestations.

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.

Purpose Injection of pharmacotherapy into the suprachoroidal space, between the sclera and choroid, is an alternative delivery technique developed with the rationale of providing higher drug concentrations to posterior ocular structures compared with other intraocular and periocular injection procedures. This study was conducted to evaluate the safety and efficacy of suprachoroidally injected triamcinolone acetonide formulation (CLS-TA), a suspension of triamcinolone acetonide, in improving vision among patients with noninfectious uveitis complicated by macular edema (ME). Design Phase 3 masked, randomized trial. Participants One hundred sixty patients with ME secondary to noninfectious uveitis. Patients were required to have a best-corrected visual acuity (BCVA) of 5 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Snellen equivalent, 20/800) and 70 or fewer ETDRS letters read (Snellen equivalent, 20/40) in the study eye. Methods Patients were randomized 3:2 to suprachoroidally injected CLS-TA or sham treatment, with administrations at day 0 and week 12. Main Outcome Measures The primary end point was improvement from baseline of 15 or more ETDRS letters in BCVA at week 24. The secondary end point was reduction from baseline in central subfield thickness (CST) at week 24. Results In the CLS-TA arm, 47% of patients gained 15 or more ETDRS letters in BCVA versus 16% in the control arm (P Conclusions Patients in the CLS-TA study arm experienced clinically significant improvement in vision relative to the sham procedure, demonstrating the efficacy of suprachoroidal injection of CLS-TA for the treatment of ME in a vision-threatening disorder.

Purpose: This report discusses the case of an 86-year-old man with a full-thickness macular hole (FTMH) secondary to polypoidal choroidal vasculopathy (PCV) treated with bevacizumab. Methods: A case report is presented. Results: An 86-year-old man presented with a 5-month history of metamorphopsia and decreased vision in his right eye and was found to have active exudation secondary to PCV with a concurrent FTMH. After 4 treatments with intravitreal bevacizumab, the FTMH resolved without surgical intervention. Conclusions: The patient’s FTMH resolved with solely pharmacologic treatment as a result of treating his PCV with intravitreal bevacizumab. Macular hole formation secondary to PCV is a rare finding, but may be successfully treated with pharmacologic therapy without surgical intervention.

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.), Graphical abstract, This report describes the case of a previously healthy 30-year-old woman who presented with uncontrolled hypertension and renal failure. This case emphasizes…

PURPOSE: To assess the prevalence of retinopathy and its association with systemic morbidity and laboratory indices of coagulation and inflammatory dysfunction in severe COVID-19. DESIGN: Retrospective, observational cohort study. METHODS: Adult patients hospitalized with severe COVID-19 who underwent ophthalmic examination from April to July 2020 were reviewed. Retinopathy was defined as one of the following: 1) Retinal hemorrhage; 2) Cotton wool spots; 3) Retinal vascular occlusion. We analyzed medical comorbidities, sequential organ failure assessment (SOFA) scores, clinical outcomes, and laboratory values for their association with retinopathy. RESULTS: Thirty-seven patients with severe COVID-19 were reviewed, the majority of whom were female (n = 23, 62%), Black (n = 26, 69%), and admitted to the intensive care unit (n = 35, 95%). Fourteen patients had retinopathy (38%) with retinal hemorrhage in 7 (19%), cotton wool spots in 8 (22%), and a branch retinal artery occlusion in 1 (3%) patient. Patients with retinopathy had higher SOFA scores than those without retinopathy (8.0 vs. 5.3, p = .03), higher rates of respiratory failure requiring invasive mechanical ventilation and shock requiring vasopressors (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.

Evaluate a single suprachoroidal injection of a proprietary triamcinolone acetonide suspension, CLS-TA, in subjects with macular edema due to noninfectious uveitis.Randomized, controlled, masked Phase 2 study. Safety and efficacy of a single suprachoroidal injection of CLS-TA (4.0 and 0.8 mg in a 4:1 ratio) were assessed at 1 and 2 months after injection. The primary efficacy endpoint was change in central subfield thickness from baseline to Month 2, assessed by spectral domain optical coherence tomography.Twenty-two adults were enrolled. The primary endpoint was met in subjects who received suprachoroidal injection of CLS-TA 4.0 mg, mean central subfield thickness significantly decreased from baseline by 135 µm and 164 µm at Month 1 (P = 0.0056) and Month 2 (P = 0.0017), respectively. At Month 2, 69% of subjects who received 4.0 mg experienced ≥20% reduction in central subfield thickness, and 65% had improvement of best-corrected visual acuity of ≥5 Early Treatment Diabetic Retinopathy Study letters, with a mean improvement of 9.2 letters (P = 0.0004). Safety analyses supported acceptable safety/tolerability, with no corticosteroid-related increases in intraocular pressure.A single suprachoroidal injection of CLS-TA (4.0 mg; 0.1 mL) in subjects with macular edema due to noninfectious uveitis was well-tolerated, significantly reduced central subfield thickness from baseline at 2 months, and significantly improved visual acuity.

Purpose To describe presenting clinical features and surgical techniques that are associated with successful surgical repair of pediatric rhegmatogenous retinal detachment (RRD). Design Retrospective interventional case series. Participants Two hundred twelve eyes of 191 patients 0 to 18 years of age undergoing surgical repair for RRD between 2001 and 2015 with a minimum follow-up of 3 months. Methods Patients were divided into 3 age groups (0–6 years, 7–12 years, and 13–18 years) and comparisons were made using bivariate and multivariate generalized estimating equation models. A mixed means model was used to examine visual acuity in each age group over time. Main Outcome Measures Complete reattachment of the retina at final follow-up. Results Of 212 eyes, 166 (78%) achieved total reattachment at final follow-up. Mean follow-up was 36.3 months. Rhegmatogenous retinal detachment associated with Stickler syndrome was more likely to occur in the younger cohorts (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.22–0.91), whereas RRD associated with blunt trauma was more likely to occur in the oldest cohort (OR, 2.3; 95% CI, 1.2–4.4). Subtotal RRD was more likely to be repaired successfully than total RRD (OR, 3.6; 95% CI, 1.5–8.4; P = 0.0100), and eyes with previous vitreoretinal surgery were less likely to undergo successful repair (OR, 0.30; 95% CI, 0.12–0.78; P = 0.0258). There was no significant difference between age groups in the rate of surgical success (P = 0.55). There was a significantly higher success rate with primary scleral buckle (SB; 63%; OR, 2.2; 95% CI, 1.1–4.5) and combined SB plus pars plana vitrectomy (PPV; 68%; OR, 2.3; 95% CI, 1.1–5.1) compared with PPV alone (51%). Conclusions Most pediatric patients with RRD achieved complete reattachment with surgery. Success was more common in patients with a subtotal RRD at presentation. Previous vitreoretinal surgery was a risk factor for failure. Younger patients were more likely to demonstrate RRD involving the macula, but there was no difference between age groups in successful reattachment at final follow-up. Primary PPV showed a lower rate of success than SB or combined SB plus PPV.

Purpose To investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD). Design Retrospective analysis of a prospective cohort study. Participants Of the 4203 Age-Related Eye Disease Study 2 (AREDS2) participants, 391 eyes (325 participants) had DPED without late AMD at the time of DPED detection. Genetic analyses included 120 white AREDS2 participants and 145 Age-Related Eye Disease Study (AREDS) participants with DPED. Methods Baseline and annual stereoscopic fundus photographs were graded centrally to detect DPED, a well-defined yellow elevated mound of confluent drusen ≥433 μm in diameter, and to evaluate progression rates to late AMD: geographic atrophy (GA) and neovascular (NV)-AMD. Five single nucleotide polymorphisms (CFH [rs10611670], C3 [rs2230199], CFI [rs10033900], C2/CFB [rs114254831], ARMS2 [rs10490924]) and genetic risk score (GRS) group were investigated for association with DPED development. Kaplan–Meier analyses and multivariable proportional hazard regressions were performed. Main Outcome Measures Progression rates to late AMD and decrease of ≥3 lines in visual acuity (VA) from the time of DPED detection; association of rate of DPED development with genotype. Results Mean (standard deviation [SD]) follow-up time from DPED detection was 4.7 (0.9) years. DPED was associated with increased risk of progression to late AMD (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.98–2.82; P Conclusions This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.

"The EVICT study was the first study to demonstrate a step-wise approach on how to safely screen EVD survivors for cataract surgery, providing evidence that vision restoration though surgical management was safe and feasible in this cohort of EVD survivors".

Purpose To review the evidence on the safety and efficacy of anti-vascular endothelial growth factor (VEGF) therapies for the treatment of neovascular age-related macular degeneration (AMD). Methods A literature search of the PubMed and Cochrane Library databases was last conducted in February 2017; there were no date restrictions, and the search was limited to studies published in English. The combined searches yielded 191 citations, 28 of which were selected because they were clinical trials and were deemed clinically relevant for the Ophthalmic Technology Assessment Committee Retina/Vitreous Panel to review in full. The panel methodologist then assigned a level of evidence rating to each study. Results Sixteen of the 28 citations provided level I evidence supporting the use of anti-VEGF agents for neovascular AMD, including intravitreal ranibizumab, aflibercept, and bevacizumab. Eight studies reviewed provided level II evidence, and 4 studies provided level III evidence, but only the level I studies are included in this assessment. There are long-term follow-up data on the efficacy of ranibizumab and bevacizumab (≥5 years), but these data are subject to the bias of incomplete follow-up. Conclusions Review of the literature indicates that intravitreal injection of anti-VEGF therapy is safe and effective for neovascular AMD over 2 years, the period for which data are available. Further research is needed to evaluate the long-term safety and comparative efficacy of these agents.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, and juvenile idiopathic associated uveitis (JIA-U) is the most frequently noted extra-articular manifestation. JIA-U can present asymptomatically and lead to ocular complications, so regular screening and monitoring are needed to prevent potentially sight-threatening sequelae. Topical glucocorticoids such as prednisolone acetate are usually the first line of treatment for anterior uveitis associated with JIA-U, but long-term use may be associated with cataract, ocular hypertension and glaucoma. Disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate allow tapering of the corticosteroids to prevent long-term complications. Biologic therapies have been increasingly used as targeted therapies for JIA-U, particularly monoclonal antibodies targeting the proinflammatory cytokine TNF-α such as adalimumab and infliximab. One recent, multicenter, prospective, randomized clinical trial provided evidence of the efficacy of adalimumab with methotrexate for JIA-U compared to methotrexate alone. Another clinical trial studying the interleukin-6 inhibitor tocilizumab for JIA-U showed promise in tapering topical corticosteroids. Additionally, JAK inhibitors are emerging biologic therapies for JIA-U in patients refractory to TNF-α inhibitors, with a clinical trial assessing the efficacy of baricitinib for JIA-U underway. While clinical trials on these novel biologics are limited, further investigation of these agents may provide additional therapeutic options for JIA-U.

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.

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.

Background Following 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 findings Given 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/Significance The 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.

Acute retinal necrosis (ARN) is a devastating syndrome characterized by panuveitis, retinal necrosis, and a high rate of retinal detachment that may result in poor visual outcomes if not promptly diagnosed and treated. ARN is most commonly caused by viruses with the herpesvirus family. Etiologies include varicella-zoster virus, herpes simplex virus, and cytomegalovirus, and may be promptly diagnosed by polymerase chain reaction testing of aqueous or vitreous fluid. The true incidence of ARN is not known due to its rarity; as a result, clinical treatment is often guided by retrospective case series, case reports, and expert opinion. Standard of care has evolved over time but currently includes a combination of systemic and intravitreal antiviral in conjunction with topical or oral steroids and surgical therapy as needed. Combination therapy may reduce the rate of severe vision loss and increase the rate of visual acuity gain, although further studies are needed in this area. In particular for patients with mild to moderate disease, combination therapy may reduce the rate of retinal detachment. Adjunctive therapies including oral corticosteroid and prophylactic laser barricade are incompletely studied, but corticosteroid in particular, may reduce inflammation, which also is involved in the severe disease pathogenesis observed in ARN. This review discusses the advances in diagnosis and treatment of ARN, including management with combination antiviral medication and surgical interventions.

Pediatric uveitis can lead to sight-threatening complications and can impact quality of life (QoL) and functioning. We aimed to examine health-related QoL, mental health, physical disability, vision-related functioning (VRF), and vision-related QoL in children with juvenile idiopathic arthritis (JIA), JIA-associated uveitis (JIA-U), and other noninfectious uveitis. We hypothesized that there will be differences based on the presence of eye disease.A multicenter cross-sectional study was conducted at four sites. Patients with JIA, JIA-U, or noninfectious uveitis were enrolled. Patients and parents completed the Pediatric Quality of Life Inventory (PedsQL; health-related QoL), the Revised Childhood Anxiety and Depression Scale (RCADS; anxiety/depression), the Childhood Health Assessment Questionnaire (C-HAQ; physical disability), and the Effects of Youngsters' Eyesight on Quality of Life (EYE-Q) (VRF/vision-related QoL). Clinical characteristics and patient-reported outcome measures were compared by diagnosis.Of 549 patients, 332 had JIA, 124 had JIA-U, and 93 had other uveitis diagnoses. Children with JIA-U had worse EYE-Q scores compared to those with JIA only. In children with uveitis, those with anterior uveitis (JIA-U and uveitis only) had less ocular complications, better EYE-Q scores, and worse C-HAQ and PedsQL physical summary scores compared to those with nonanterior disease. In children with anterior uveitis, those with JIA-U had worse PedsQL physical summary and C-HAQ scores than anterior uveitis only. Further, EYE-Q scores were worse in children with bilateral uveitis and more visual impairment. There were no differences in RCADS scores among groups.We provide a comprehensive outcome assessment of children with JIA, JIA-U, and other uveitis diagnoses. Differences in QoL and function were noted based on underlying disease. Our results support the addition of a vision-specific measure to better understand the impact of uveitis.

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.

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 Effects of Youngsters' Eyesight on Quality of Life (EYE-Q) questionnaire measures vision-related functioning (VRF) and vision-related quality of life (VRQoL) in children with uveitis. Our aim was to revise the alpha version of the EYE-Q to refine VRF and VRQoL subscales and to assess the validity of the EYE-Q.Children with juvenile idiopathic arthritis (JIA), JIA-associated uveitis, and other noninfectious uveitis were enrolled. Patients and parents completed the EYE-Q, Pediatric Quality of Life Inventory (overall quality of life), and Childhood Health Assessment Questionnaire (physical functioning). The development site completed the alpha version of the EYE-Q, and the composite sites completed the beta version. We compared item-subscale correlations, internal consistency, and construct and discriminant validity among the different versions.Of the 644 patients enrolled, 61.6% completed the alpha version, and 38.4% the beta version of the EYE-Q. Mean ± SD patient age was 11.1 ± 4.2 years, and 70% were female. Fewer White patients (73.5%) completed the alpha version compared to the beta version (86.2%; P 0.001). With the exception of patient-reported VRF, both versions had similar item-subscale correlations. Version comparisons on scale internal consistencies indicated significant differences for parent- and patient-reported VRF, but each scale had a Cronbach's α of0.80 beta. When data were combined, the EYE-Q showed significant differences between JIA-only and uveitis patients on all parent and patient scores, except for patient-reported VRF.The EYE-Q appears to be a valid measure of VRF and VRQoL in pediatric uveitis. Our results suggest it may be used as an outcome measure in multicenter pediatric uveitis studies.

INTRODUCTION: Pediatric uveitis comprises a range of ocular inflammatory diseases that may lead to vision impairment, often due to ocular complications from the disease itself or side effects of therapies. The impact on vision, visual functioning, and vision-related quality-of-life over the lifetime horizon can be substantial, underscoring the importance of appropriate ophthalmic evaluation, diagnostic testing and treatment. This review focuses on the anatomic classification, laboratory diagnosis, associated systemic diseases, and management of pediatric uveitis. AREAS COVERED: A review of the literature was performed to synthesize our current understanding of the anatomic classification of pediatric uveitis, disease epidemiology, associated systemic diseases, and management principles. We also review important corticosteroid-sparing strategies including non-biologic and biologic agents such as the anti-tumor necrosis factor (TNF)-alpha family of medications, given their key role in the treatment of pediatric uveitis, particularly juvenile idiopathic arthritis (JIA). Recent advances in the assessment of vision-related quality-of-life using the Effects of Youngsters’ Eyesight on Quality of Life (EYE-Q) instrument are discussed. EXPERT OPINION: Pediatric uveitis can lead to long-term vision impairment if not appropriately screened and treated. JIA is the most common systemic disease associated with uveitis, is typically asymptomatic, and thus requires rigorous screening to detect uveitis and avoid secondary ocular complications. While topical and systemic corticosteroids are useful for the acute treatment of uveitis, the disease chronicity of many pediatric uveitis syndromes including JIA, often warrants early escalation of therapy to immunosuppressive medications including methotrexate (MTX) and anti-TNF-alpha inhibitors. Future directions include an improved understanding of risk factors for uveitis and better metrics to evaluate the impact of disease on vision-related quality-of-life of pediatric uveitis patients.

Purpose of review To highlight the lessons learned from the Ebola outbreak that may inform our approach to the COVID-19 pandemic, particularly related to the widespread disruption of healthcare, ophthalmic disease manifestations, and vision health systems strengthening for future outbreaks. Recent findings Coronavirus disease 2019 (COVID-19), first detected in China in December 2019, has become a worldwide health emergency, with significant disruption of all aspects of society, including travel, business, and medical care. Although this pandemic has had unprecedented effects on healthcare delivery in the United States, experiences from recent Ebola virus disease (EVD) outbreaks in Africa provide insight and inform our approach to COVID-19 and outbreak preparedness. Like COVID-19, the rapid emergence of Ebola required new clinical and surgical approaches to understand its associated spectrum of ophthalmic complications and the potential for Ebola viral persistence within the eye and in tear film. Recent reports of ophthalmic findings associated with COVID-19 include conjunctivitis, retinopathy, and molecular evidence of virus within the tear film in a minority of cases. Yet, more rigorous approaches to understand ophthalmic disease and transmission risk associated with COVID-19 are needed. Gaps also remain in our understanding of eye disease associated with other high priority emerging infectious diseases including Nipah, Lassa fever, Marburg virus, and others. Summary Thoroughly understanding the ophthalmic findings and transmission risk associated with COVID-19 is paramount during this pandemic, providing additional measures of safety while resuming ophthalmic care for all patients. Vision health systems preparedness measures developed during recent EVD outbreaks and the current pandemic provide models for ophthalmic clinical practice, research, and education, as we continue to address COVID-19 and future emerging infectious disease threats.

Purpose : To determine classification criteria for intermediate uveitis, non-pars planitis type (IU- NPP, also known as undifferentiated intermediate uveitis) Design : Machine learning of cases with IU-NPP and 4 other intermediate uveitides. Methods : Cases of intermediate uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation set. Results : Five hundred eighty-nine of cases of intermediate uveitides, including 114 cases of IU-NPP, were evaluated by machine learning. The overall accuracy for intermediate uveitides was 99.8% in the training set and 99.3% in the validation set (95% confidence interval 96.1, 99.9). Key criteria for IU-NPP included unilateral or bilateral intermediate uveitis with neither 1) snowballs in the vitreous nor 2) snowbanks on the pars plana. Other key exclusions included: 1) multiple sclerosis, 2) sarcoidosis, and 3) syphilis. The misclassification rates for pars planitis were 0 % in the training set and 0% in the validation set, respectively. Conclusions : The criteria for IU-NPP had a low misclassification rate and appeared to perform well enough for use in clinical and translational research.

Introduction The largest Ebola virus (EBOV) outbreak occurred from 2013 - 2016 in West Africa and consequently resulted in the largest cohort of Ebola virus disease (EVD) survivors to date. Ocular disease is among the most common sequelae reported in EVD survivors. This review discusses the prevalence, manifestations, pathogenesis, diagnosis and management of EVD-related ocular disease. Areas covered An extensive review of the literature was performed to detail the prevalence and manifestations of EVD-related ocular disease. We also review current eye screening and treatment strategies and our current understanding and approach to invasive ophthalmic procedures including surgery. Expert opinion The ocular sequelae of EVD can lead to vision impairment or blindness, if untreated. Keys to the prevention of such an outcome include timely evaluation and access to appropriate ophthalmic care. The persistence of EBOV in the eye and other immune-privileged sites is the subject of ongoing investigation, but should not be a barrier to care if appropriate screening and biosafety measures are taken. Improved understanding of the pathogenesis of this condition and ongoing clinical care are needed for EVD survivors at-risk for ocular complications.

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.

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.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease associated with uveitis. JIA-associated uveitis (JIA-U) is typically asymptomatic, chronic, and can lead to sight-threatening complications. This review will provide approaches to improve the diagnosis and outcomes of children with JIA-U. AREAS COVERED: We will provide updates on risk factors for uveitis onset and ocular complications, improvements in the ophthalmic screening schedule for uveitis detection, and potential strategies to advance the diagnosis and monitoring of JIA-U using advanced ophthalmic imaging and diagnostic equipment and laboratory biomarkers. EXPERT OPINION: There is a lack of high-quality research in JIA-U and few randomized controlled trials, underscoring the urgent need for further studies in this population. Early uveitis diagnosis combined with timely and appropriate treatment can improve visual outcomes. Improved knowledge of uveitis pathogenesis, risk factors for uveitis onset, measurement of uveitis outcomes, and optimal treatment are crucial.

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.

Macular edema is the most frequent cause of visual deterioration in noninfectious uveitis. The treatment of noninfectious uveitis with associated macular edema commonly includes systemic or locally administered corticosteroids, with long-term use limited by significant side effects. The need for a treatment with an improved safety profile has driven the development of a novel ophthalmic therapy: a proprietary triamcinolone acetonide suspension (CLS-TA) administered in the suprachoroidal space (XIPERE(™); Clearside Biomedical, Alpharetta, GA, USA). Suprachoroidal delivery of corticosteroids allows higher steroid concentration in the posterior segment and decreases the risk of other adverse ocular events. Recent results from the PEACHTREE trial (ClinicalTrials.gov Identifier: NCT02595398), a phase III trial with two suprachoroidal injections of CLS-TA at 0 and 12 weeks with follow up lasting 24 weeks, showed the significant improvement in visual acuity and reduction in central subfield thickness, all without increasing the risk of elevated intraocular pressure or accelerated cataract progression.

Purpose To analyze the prevalence, incidence, and clinical characteristics of eyes with geographic atrophy (GA) in age-related macular degeneration (AMD), including clinical and genetic factors affecting enlargement. Design Prospective cohort study within a controlled clinical trial. Participants Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50–85 years. Methods Baseline and annual stereoscopic color fundus photographs were evaluated for GA presence and area. Analyses included GA prevalence and incidence rates, Kaplan-Meier rates, mixed-model regression, and multivariable analysis of the square root of GA, area adjusted for covariates, including clinical/imaging characteristics and genotype. Main Outcome Measures (1) Presence or development of GA; (2) change in the square root of GA area over time. Results At baseline, 517 eyes (6.2%) of 411 participants (9.8%) had pre-existing GA (without neovascular AMD), with the following characteristics: 33% central, 67% noncentral; and the following configurations: 36% small, 26% solid/unifocal, 24% multifocal, 9% horseshoe/ring, and 6% indeterminate. Of the remaining 6530 eyes at risk, 1099 eyes (17.3%) of 883 participants developed incident GA without prior neovascular disease during mean follow-up of 4.4 years. The Kaplan-Meier rate of incident GA was 19% of eyes at 5 years. In eyes with incident GA, 4-year risk of subsequent neovascular AMD was 29%. In eyes with incident noncentral GA, 4-year risk of central involvement was 57%. GA enlargement rate (following square root transformation) was similar in eyes with pre-existing GA (0.29 mm/year; 95% confidence interval 0.27–0.30) and incident GA (0.28 mm/year; 0.27–0.30). In the combined group, GA enlargement was significantly faster with noncentrality, multifocality, intermediate baseline size, and bilateral GA (P Conclusions Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.

To review the systemic and ocular complications of Bartonella spp. infections specifically cat scratch disease, encompassing epidemiology, laboratory diagnostics, ophthalmic imagining, and treatment.Recent studies have shown that ocular manifestations occur in approximately 4.4% of cat scratch disease patients. The annual prevalence is lower than previously reported to be approximately 12 500 cases annually. Mainstay treatment continues to be oral antibiotics with and without corticosteroids and is dependent on associated systemic manifestations, age, and patient immune status. More recently anti-VEGF agents have been used for complications such as cystoid macular edema and choroidal neovascularization.Bartonella spp. infections continue to be a common cause uveitis with ophthalmic manifestations ranging from neuroretinits, vascular occlusions, to choroidal granulomas. Review of associated risk factors including contact with feline reservoirs will aid in recognition and diagnosis of this disease entity. Laboratory diagnostics continue to improve to help with the diagnosis of this entity.

In the wake of the international Ebola virus disease (EVD) outbreak from 2014 to 2016, thousands of EVD survivors are at-risk of ophthalmic manifestations, as well as systemic sequelae including arthralgias, abdominal pain, psychosocial stressors, and risk of viral persistence in immune-privileged organs. Ophthalmic manifestations in EVD survivors include a spectrum of disease ranging from anterior uveitis to panuveitis, which confers a high risk of vision impairment and blindness, particularly given the access and resource limitations for ophthalmic subspecialty care in West Africa. Clinical studies in EVD survivors, animal models of EVD and translational investigation, have provided early insight into eye disease pathogenesis. Specifically, ocular inflammation recently observed in EVD survivors is thought to involve direct viral infection, inflammation, and tissue edema. Future research is needed to understand the timing of uveitis onset and management strategies, including the role of antiviral and anti-inflammatory therapies.

Purpose To evaluate postoperative pain level using a supplemental peribulbar injection at the conclusion of retinal surgery. Design Prospective, parallel-assigned, single-masked, randomized clinical trial. Participants Fifty-eight patients undergoing scleral buckle, vitrectomy, or combined surgery. Methods In a single academic institutional practice, 58 patients undergoing scleral buckle, vitrectomy, or combined surgery were enrolled. Exclusion criteria included those with a risk for glaucoma, a pre-existing chronic pain disorder, among others. Patients were assigned randomly to receive a postoperative peribulbar formulation of either bupivacaine, triamcinolone acetonide, and cefazolin (group A) or bupivacaine, balanced salt solution, and cefazolin (group B). The postoperative pain score and ocular motility were assessed by a masked observer on the first postoperative day. Main Outcome Measures The primary outcome measure was the postoperative pain score. Secondary outcome measures included oral analgesic use, ocular motility, and intraocular pressure (IOP). Results The mean pain scores were 2.8±2.9 for group A and 3.8±2.6 for group B (P = 0.095). Pain was absent in 28% of group A patients versus 14% of group B patients (P = 0.11). Group A required less narcotic pain medication (hydroxycodone: group A, 0.7±3 mg vs. group B, 3±6 mg; P = 0.05; oxycodone: group A, 7±7 mg vs. 9±13 mg; P = 0.2) than group B. Motility was full in group B and limited in group A (P ≤ 0.001), with no differences in mean IOP measurements at any point after surgery. Conclusions We did not demonstrate a statistically significant reduction in mean postoperative pain scores. However, patients in group A required less hydroxycodone use and had greater akinesia, suggesting prolonged neural blockade.

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, Highlights • Ebola virus disease (EVD) survivors are at-risk for severe vision impairment due to uveitis and subsequent cataract development. • Fifty EVD survivors underwent ocular fluid sampling and tested negative for Ebola virus by RT-PCR. • Thirty-four survivors underwent cataract surgery with excellent safety measures and vision restorative outcomes. Ebola virus disease (EVD) survivors are at high risk for uveitis, an inflammatory condition affecting the eye that may lead to severe vision impairment, often from cataract. Because persistent Ebola virus (EBOV) has been identified within the immune privileged eye, understanding the prevalence of intraocular EBOV persistence is significant for patients, providers, and public health policy. In this study, 50 EVD survivors tested negative for EBOV by RT-PCR of their intraocular fluid. Thirty-four underwent cataract surgery with vision restorative outcomes. These findings improve our ability to impact vision care and quality-of-life for thousands of EVD survivors at-risk for eye disease.

This review provides a summary of our current understanding of the ophthalmic manifestations of Ebola virus disease (EVD), pathogenesis, treatment options and directions for future study. The individual, public health and global health implications of eye disease in EVD survivors are discussed.The West Africa EVD outbreak was of unprecedented magnitude, leading to the largest survivor cohort since the first documented EVD outbreak in 1976. Because of the magnitude of the recent outbreak, thousands of survivors are at-risk of systemic and ophthalmic sequelae termed the 'post Ebola virus disease syndrome'. Uveitis is the most common finding during EVD convalescence and may lead to severe vision impairment or blindness in 40% of affected individuals. Ocular complications leading to vision loss include cataract, retinal scarring, optic neuropathy, hypotony and phthisis bulbi. The pathogenesis of eye disease in EVD survivors likely involves Ebola virus persistence, severe inflammation and tissue edema, which present as acute, rapidly progressive disease or chronic, smoldering disease. Further studies into disease pathogenesis including mechanisms of viral persistence may provide guidance into therapies for uveitis secondary to EVD.Uveitis is the most common ophthalmic finding in EVD survivors and can lead to vision loss. Further studies into the clinical manifestations and mechanisms of disease are needed to improve therapies for EVD survivors who often have limited access to ophthalmic medical and surgical care.