Pars plana vitrectomy with internal limiting membrane flap versus pars plana vitrectomy with conventional internal limiting membrane peeling for large macular hole.

BACKGROUND: Macular hole (MH) is a full-thickness defect in the central portion of the retina that causes loss of central vision. According to the usual definition, a large MH has a diameter greater than 400 µm at the narrowest point. For closure of MH, there is evidence that pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling achieves better anatomical outcomes than standard PPV. PPV with ILM peeling is currently the standard of care for MH management; however, the failure rate of this technique is higher for large MHs than for smaller MHs. Some studies have shown that the inverted ILM flap technique is superior to conventional ILM peeling for the management of large MHs. OBJECTIVES: To evaluate the clinical effectiveness and safety of pars plana vitrectomy with the inverted internal limiting membrane flap technique versus pars plana vitrectomy with conventional internal limiting membrane peeling for treating large macular holes, including idiopathic, traumatic, and myopic macular holes. SEARCH METHODS: The Cochrane Eyes and Vision Information Specialist searched CENTRAL, MEDLINE, Embase, two other databases, and two trials registries on 12 December 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated PPV with ILM peeling versus PPV with inverted ILM flap for treatment of large MHs (with a basal diameter greater than 400 µm at the narrowest point measured by optical coherence tomography) of any type (idiopathic, traumatic, or myopic). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane and assessed the certainty of the body of evidence using GRADE. MAIN RESULTS: We included four RCTs (285 eyes of 275 participants; range per study 24 to 91 eyes). Most participants were women (63%), and of older age (range of means 59.4 to 66 years). Three RCTs were single-center trials, and the same surgeon performed all surgeries in two RCTs (the third single-center RCT did not report the number of surgeons). One RCT was a multicenter trial (three sites), and four surgeons performed all surgeries. Two RCTs took place in India, one in Poland, and one in Mexico. Maximum follow-up ranged from three months (2 RCTs) to 12 months (1 RCT). No RCTs reported conflicts of interest or disclosed financial support. All four RCTs enrolled people with large idiopathic MHs and compared conventional PPV with ILM peeling versus PPV with inverted ILM flap techniques. Variations in technique across the four RCTs were minimal. There was some heterogeneity in interventions: in two RCTs, all participants underwent combined cataract-PPV surgery, whereas in one RCT, some participants underwent cataract surgery after PPV (the fourth RCT did not mention cataract surgery). The critical outcomes for this review were mean best-corrected visual acuity (BCVA) and MH closure rates. All four RCTs provided data for meta-analyses of both critical outcomes. We assessed the risk of bias for both outcomes using the Cochrane risk of bias tool (RoB 2); there were some concerns for risk of bias associated with lack of masking of outcome assessors and selective reporting of outcomes in all RCTs. All RCTs reported postoperative BCVA values; only one RCT reported the change in BCVA from baseline. Based on evidence from the four RCTs, it is unclear if the inverted ILM flap technique compared with ILM peeling reduces (improves) postoperative BCVA measured on a logarithm of the minimum angle of resolution (logMAR) chart at one month (mean difference [MD] -0.08 logMAR, 95% confidence interval [CI] -0.20 to 0.05; P = 0.23, I2 = 65%; 4 studies, 254 eyes; very low-certainty evidence), but it may improve BCVA at three months or more (MD -0.17 logMAR, 95% CI -0.23 to -0.10; P < 0.001, I2 = 0%; 4 studies, 276 eyes; low-certainty evidence). PPV with an inverted ILM flap compared to PPV with ILM peeling probably increases the proportion of eyes achieving MH closure (risk ratio [RR] 1.10, 95% CI 1.02 to 1.18; P = 0.01, I2 = 0%; 4 studies, 276 eyes; moderate-certainty evidence) and type 1 MH closure (RR 1.31, 95% CI 1.03 to 1.66; P = 0.03, I² = 69%; 4 studies, 276 eyes; moderate-certainty evidence). One study reported that none of the 38 participants experienced postoperative retinal detachment. AUTHORS' CONCLUSIONS: We found low-certainty evidence from four small RCTs that PPV with the inverted ILM flap technique is superior to PPV with ILM peeling with respect to BCVA gains at three or more months after surgery. We also found moderate-certainty evidence that the inverted ILM flap technique achieves more overall and type 1 MH closures. There is a need for high-quality multicenter RCTs to ascertain whether the inverted ILM flap technique is superior to ILM peeling with regard to anatomical and functional outcomes. Investigators should use the standard logMAR charts when measuring BCVA to facilitate comparison across trials.

ASSOCIATION OF ORAL MONTELUKAST WITH REDUCED ODDS OF DEVELOPING EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: This study was conducted to evaluate the association of oral montelukast, selective antagonism for cysteinyl leukotriene receptor 1, with reduced odds of exudative age-related macular degeneration (exAMD) development. METHODS: This case-control study was conducted using institutional cohort finder tool, and included 1913 patients with exAMD (ICD: H35.32 and 362.52) and 1913 age- and gender-matched control subjects without exAMD. Subanalysis among 1913 exAMD and 324 nonexudative AMD was also conducted. RESULTS: A total of 47 (2.5%) exAMD cases were identified to have a history of oral montelukast use before exAMD diagnosis, compared with 84 (4.4%) controls. Montelukast usage was significantly associated with reduced odds of exAMD in the multivariable analysis (adjusted odds ratio [OR]: 0.50, 95% confidence interval: 0.31-0.80) and nonsteroidal anti-inflammatory drug usage (adjusted OR: 0.69). Caucasian race, history of smoking, and nonexudative macular degeneration in either eye were also found to have a significant relationship with increased odds of exAMD. In the subanalysis, montelukast usage showed significant association with reduced odds of developing exAMD from nonexudative AMD (adjusted OR: 0.53, 95% confidence interval: 0.29-0.97) and the presence of atopic disease (adjusted OR: 0.60). CONCLUSION: The study results suggested that oral montelukast is linked to reduced odds of exAMD development.

Teprotumumab for the Treatment of Recalcitrant Thyroid Eye Disease.

PURPOSE: Teprotumumab, an insulin-like growth factor 1 receptor monoclonal antibody, is FDA-approved to treat thyroid eye disease (TED). The initial clinical trials excluded patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose >1 gm), or prior biologic treatment. Information on the use of teprotumumab for patients who failed prior therapy is limited. Our purpose is to characterize the efficacy of teprotumumab for the treatment of recalcitrant TED. METHODS: This is a multicenter retrospective study of all patients treated with teprotumumab for moderate-to-severe TED after failing conventional therapy with corticosteroids, orbital radiation, surgical decompression, biologics, or other steroid-sparing medications. Treatment failure was defined as an incomplete response to or reactivation after previous treatment. Only patients who received at least 4 infusions of teprotumumab were included in the analysis. Primary outcome measures comprised proptosis response (≥2 mm reduction in the study eye without a similar increase in the other eye), clinical activity score (CAS) response (≥2-point reduction in CAS), and diplopia response (≥1 point improvement in Gorman diplopia score in patients with baseline diplopia) following treatment. Adverse events and risk factors for recalcitrant disease were also evaluated. RESULTS: Sixty-six patients were included in this study, 46 females and 20 males. Average age was 59.3 years (range 29-93). The mean duration of disease from TED diagnosis to first infusion was 57.8 months. The proptosis, CAS, and diplopia responses in this recalcitrant patient population were 85.9%, 93.8%, and 69.1%, respectively. Patients experienced a mean reduction in proptosis of 3.1 ± 2.4 mm and a mean improvement in CAS of 3.8 ± 1.6. Patients who underwent prior decompression surgery experienced a statistically significant decrease in diplopia response (46.7% vs. 77.5%, p = 0.014) and proptosis response (75.0% vs. 90.9%, p = 0.045) when compared with nondecompression patients. Additionally, there were no significant differences in proptosis, CAS, and diplopia responses between patients with acute (defined as disease duration <1 year) versus chronic (disease duration ≥1 year) TED. While most adverse events were mild to moderate, 4 patients reported serious adverse events related to persistent hearing loss. CONCLUSIONS: Patients with recalcitrant TED demonstrated a significant improvement after teprotumumab in each of the primary study outcomes. The degree of proptosis reduction, diplopia response, and CAS improvement in the recalcitrant group were similar to those of treatment-naïve patients from the pivotal clinical trials. Patients with a prior history of orbital decompression, however, demonstrated poor improvement in diplopia and less reduction in proptosis than surgery naïve patients. These results indicate that teprotumumab is a treatment option for the treatment of patients with TED recalcitrant to prior medical therapies.

The rapid N-wave as a potentially useful measure of the photopic negative response.

PURPOSE: The photopic negative response (PhNR) correlates with ganglion cell function and has previously been examined as an indicator of glaucomatous optic nerve damage. However, it is a prolonged response that is measured against baseline, and its clinical utility has been limited by extensive variability, poor repeatability, and baseline instability. We have observed a distinct brief negative wave ("N-wave") commonly present within the slow PhNR trough, which may provide practical and analytic advantages as a clinical measure. METHODS: We reviewed data from an interventional trial of 59 glaucoma patients who had 4 exams over an 8-month period. The PhNR was recorded with standard ISCEV stimuli (1 Hz and in some cases 4 Hz stimulation), and N-waves were measured manually, relative to return to baseline. RESULTS: N-waves, when present, could be measured easily despite shifting baselines and a degree of background noise. The PhNR median amplitude centered around 18 µV, while the N-wave median centered around 7 µV, with a distribution of responses skewed toward low or zero amplitudes. CONCLUSIONS: The N-wave appears to be a component of the longer PhNR, though its exact origin and significance remain unclear. As a rapid waveform that is independent of baseline, the N-wave is in many ways easier to measure accurately than the slower PhNR, which is highly dependent on baseline stability. The N-wave may prove useful clinically if further studies can optimize its stimulation, show its behavior in normal individuals and find correlation with markers of optic nerve disease.

SEQUENTIAL CHANGES IN HYDROXYCHLOROQUINE RETINOPATHY UP TO 20 YEARS AFTER STOPPING THE DRUG: Implications for Mild Versus Severe Toxicity.

PURPOSE: To characterize the stability or progression of different stages of hydroxychloroquine (HCQ) retinopathy up to 20 years after stopping the drug. METHODS: We reviewed findings from 13 patients with initial HCQ retinopathy classified as early (patchy photoreceptor damage), moderate (ring of photoreceptor thinning or scotoma), or severe (retinal pigment epithelial [RPE] damage). Patients had been off HCQ for as many as 14 years at initial examination and were subsequently followed for 5 years to 8 years with repeated fundus autofluorescence and spectral domain optical coherence tomography. RESULTS: Early and moderate cases stabilized in fundus autofluorescence appearance, foveal thickness, ellipsoid zone line length, and visual acuity for up to 9 years after stopping HCQ. By contrast, severe cases demonstrated a continual loss of these parameters for up to 20 years off the drug. The presence of RPE damage at initial examination predicted progressive retinopathy over many years. CONCLUSION: The steady progression of severe HCQ retinopathy in eyes showing RPE damage after drug cessation suggests a metabolic insult that chronically destabilizes rather than destroys cellular function, with a clinical course resembling that of genetic dystrophies. Our findings stress the importance of early detection to minimize progression and visual loss.

The Role of Corticosteroids and Immunomodulatory Therapy in the Management of Infectious Uveitis.

PURPOSE: The index review aims to provide an update on the role of corticosteroids and steroid-sparing immunomodulatory therapy (IMT) in managing patients with infectious uveitis. METHOD: Narrative literature review. RESULTS: Corticosteroids and immunomodulatory therapy (IMT) focus on the host defense system instead of the pathogen, adjusting exaggerated inflammatory reactions to reduce potential harm to ocular tissues. Systemic or local corticosteroids are primarily selected as adjunctive medication for infectious uveitis. Concomitant corticosteroids have also been used in cases of paradoxical worsening in ocular tuberculosis and immune recovery uveitis in cytomegalovirus (CMV) retinitis. While there is no well-established evidence to support the use of IMT in infectious uveitis, it is occasionally used in clinical settings to treat persistent inflammation following resolution of infection such as cases of ocular tuberculosis and ocular syphilis where an insufficient response is observed with corticosteroids. CONCLUSION: There is no consensus on the position of immunomodulatory therapy in the management of infectious uveitis with different etiologies. The index review provides an overview of available adjunctive corticosteroids and IMT options to assist clinicians in managing such disease entities more efficiently.

Birdshot Chorioretinopathy in Early Adulthood: Review of Current Literature and Case Report.

Purpose: We describe the course of a patient diagnosed with birdshot chorioretinopathy (BSCR) in early adulthood and summarize clinical findings from similar BSCR patients reported in the literature. Observations: A 37-year-old male presented to our tertiary uveitis facility with bilateral ocular discomfort, hazy vision, and floaters. Ocular examination was notable for vitritis, optic disc edema, and ovoid hypopigmented chorioretinal lesions, visible on indocyanine green chorioangiography as multiple hypocyanescent spots in the intermediate phase. Full-field electroretinography and visual evoked potential showed global retinal dysfunction and optic nerve dysfunction. Laboratory evaluations were notable only for human leukocyte antigen (HLA)-A29 positivity. The patient was diagnosed with BSCR and started on oral prednisone and eventually managed with infliximab. Conclusions and Importance: BSCR can affect patients in early adulthood. Proper diagnostic work-up, including assessing HLA-A29 positivity, is needed to manage atypical cases.

TOPOGRAPHIC OPTICAL COHERENCE TOMOGRAPHY SEGMENTATION SHOWS LIMITED ELLIPSOID ZONE RECOVERY IN MILD HYDROXYCHLOROQUINE RETINOPATHY.

PURPOSE: Optical coherence tomography (OCT) cross-sections have shown limited ellipsoid zone (EZ) improvement in mild hydroxychloroquine (HCQ) retinopathy within a few years after drug cessation. However, the extent, functional significance, and stability of such changes over time remain unclear. METHODS: We created en face EZ maps using automated pixel-by-pixel segmentation for four patients with early-moderate HCQ toxicity followed for 6-8 years after drug cessation. These maps were compared with OCT cross-sections, fundus autofluorescence, and automated 10-2 visual fields. RESULTS: One patient had no EZ line loss; one had stable EZ loss throughout follow-up; two showed 30 to 40% reduction in the area of loss, largely in the first 2 years. This limited recovery mostly occurred in regions where the EZ line was only thinned or fragmented; other similar areas did not improve. Fundus autofluorescence hyperfluorescence and visual fields did not show consistent correlation with topography. CONCLUSION: Anatomic EZ recovery, when present, was restricted to regions of mild damage and did not correlate with fundus autofluorescence or improvement in visual fields. Topographic mapping seemed no more sensitive locally than cross-sectional OCT but may aid detection and longitudinal follow-up of toxicity by showing early damage or changes in the macula that could be missed with individual cross-sections.

Hearing Dysfunction After Treatment With Teprotumumab for Thyroid Eye Disease.

PURPOSE: To characterize the frequency, severity, and resolution of hearing dysfunction in patients treated with teprotumumab for thyroid eye disease (TED). DESIGN: Prospective observational case series. METHODS: Ophthalmic examination and adverse event assessment, including otologic symptoms, were performed at baseline, after infusions 2, 4, and 8, and at 6-month follow-up in consecutive patients who received at least 4 teprotumumab infusions. Laboratory test results were collected at baseline and during treatment. Audiometry, patulous eustachian tube (PET) testing, and otolaryngology evaluation were obtained for patients with new or worsening otologic symptoms, with a subset obtaining baseline and posttreatment testing. RESULTS: Twenty-seven patients were analyzed (24 females, 3 males, average 56.3 years old). Twenty-two patients (81.5%) developed new subjective otologic symptoms, after a mean of 3.8 infusions (SD 1.8). At 39.2-week average follow-up after the last infusion, most patients with tinnitus (100%), ear plugging/fullness (90.9%), and autophony (83.3%) experienced symptom resolution, whereas only 45.5% (5 of 11) of patients with subjective hearing loss/decreased word comprehension experienced resolution. Six patients underwent baseline and posttreatment audiometry, 5 of whom developed teprotumumab-related sensorineural hearing loss (SNHL) and 1 patient also developed PET. Three of the 5 patients with teprotumumab-related SNHL had persistent subjective hearing loss at last follow-up. A prior history of hearing loss was discovered as a risk factor for teprotumumab-related SNHL (P = .008). CONCLUSIONS: Hearing loss is a concerning adverse event of teprotumumab, and its mechanism and reversibility should be further studied. Until risk factors for hearing loss are better understood, we recommend baseline audiometry with PET testing and repeat testing if new otologic symptoms develop. Screening, monitoring, and prevention guidelines are needed.

Efficacy and safety of intravitreal anti-VEGF therapy in diabetic retinopathy: what we have learned and what should we learn further?

INTRODUCTION: Diabetic retinopathy (DR) is one of the most frequent microvascular complications of diabetes that can lead to blindness. Laser treatment has been the gold standard treatment for diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) for many years. Recently, the role of vascular endothelial growth factor (VEGF) has been established in the pathogenesis of DR, and the use of intravitreal anti-VEGF therapy has gained popularity for the management of DR. AREAS COVERED: This review includes a brief overview of the efficacy and safety of currently available (bevacizumab, ranibizumab, and aflibercept) and potential future (brolucizumab, faricimab, and KSI-301) anti-VEGF agents in patients with DR based mainly on publicly available data from phase 1, 2 and 3 clinical trials. EXPERT OPINION: Clinical trials investigating the efficacy of intravitreal bevacizumab, ranibizumab, and aflibercept injections demonstrated favorable functional and anatomical outcomes in patients with DME. Moreover, the use of these anti-VEGF agents showed a significant improvement in the severity of DR. Recent clinical research for future anti-VEGF molecules aims to provide higher target-protein binding affinity and prolonged therapeutic effect. Brolucizumab, faricimab, and KSI-301 are three novel anti-VEGF agents that demonstrate promising data for the management of DME and potentially DR.

Bilateral retinal vasculitis associated with cold agglutinin disease treated with obinutuzumab and infliximab.

Purpose: To describe the clinical course and management of a patient with bilateral retinal vasculitis associated with cold agglutinin disease (CAD) treated with obinutuzumab and infliximab. Observations: A 69-year-old Hispanic woman was referred to a tertiary Uveitis Clinic with progressively worsening blurry vision, right eye (OD) worse than left eye (OS). Past ocular history was significant for epiretinal membranes in both eyes (OU). Past medical history was notable for non-specific joint disease, primarily affecting her knees bilaterally, and pulmonary symptoms (e.g., dyspnea, productive cough) of unclear etiologies one year before presentation. She had been evaluated by rheumatologists and pulmonologists and was placed on low doses of prednisone and methotrexate. Upon examination, her visual acuity was 20/40 in OD and 20/25 in OS. Anterior segment exam was unremarkable with no cell or flare in OU. Dilated fundus examination was notable for 0.5+ vitreous haze in OU and mild vessel attenuation in OU. Wide-angle fluorescein angiography (FA) revealed mild bilateral periphery peri-vasculature leakage in OU. Initial blood evaluations revealed decreased hematocrit, and positive anti-nuclear antibody. Her peripheral smear disclosed 3+ agglutination. She was initially treated with mycophenolate mofetil 1000 mg twice daily and prednisone 20 mg then referred to hematology. Further work up revealed high-titer cold agglutinin and positive thermal amplitude screen at 30 °C. Bone marrow examination demonstrated a chronic lymphocytic leukemia (CLL)-like monoclonal B-cell lymphocytosis. Anti-CD20 monoclonal antibody therapy with obinutuzumab was started in an effort to treat the underlying CLL clone and address the associated ocular vasculitis related to CAD. Three months later, after eight cycles of obinutuzumab, the patient's best- corrected visual acuity (BCVA) continued to be stable at 20/30 in OD and 20/20 in OS. However, FA showed persistent diffuse perivascular leakage. Intravenous infliximab with concurrent intravenous methylprednisolone infusions were started. After two cycles of treatment, FA showed significantly improved perivascular leakage. Visual acuity remained stable at 20/25 in OU. Conclusions and importance: Ocular involvement in CAD is rare. The index case is the first report of retinal vasculitis in a patient with CAD. Our report not only describes the unique course of CAD-related retinal vasculitis, but also introduces and underscores a successful therapeutic plan.

Efficacy and Safety of Tocilizumab in the Management of Non-Infectious Uveitis Failed with Conventional Immunomodulatory and Anti-TNFα Therapies.

PURPOSE: To determine the outcomes of intravenous (IV) tocilizumab (TCZ) in patients with non-infectious uveitis who failed with conventional immunomodulatory and anti-TNFα therapies. METHODS: Records of seven patients with non-infectious uveitis treated with monthly IV TCZ (4-10 mg/kg) or biweekly IV TCZ (8 mg/kg) were reviewed. Outcome measures were changes in visual acuity, anterior chamber cell and flare grade, vitreous haze, central subfield thickness (CST), and fluorescein angiography (FA) score. RESULTS: Ten eyes of seven patients received TCZ therapy. Median age of patients was 14 (range, 7-24) years. Median duration of TCZ therapy was 15 (range, 5-32) months. Mean CST reduced from 373 ± 101.0 µm to 298.2 ± 40.3 µm. Mean FA score reduced from 12.5 ± 4.3 to 3.6 ± 2.6. One patient developed elevated liver transaminases. CONCLUSION: IV TCZ is a potentially effective and safe therapeutic option for the management of refractory non-infectious uveitis.

Ocular Gene Therapy: A Literature Review with Special Focus on Immune and Inflammatory Responses.

Gene therapy has emerged as a research topic of choice in recent years. The eye in particular is one of few organs of the body for which gene therapy has received Food and Drug Administration approval, and it remains a field of great interest for gene therapy development. However, its associated immune and inflammatory reactions may render the treatment ineffective or harmful, which are of particular concern for the eyes due to their susceptibility to inflammation. The severity of immune and inflammatory reactions depends on the choice of vector and its route of administration. Furthermore, most preclinical and clinical studies have shown that the dose of vectors is correlated with the degree of humoral response and ocular inflammation. The route of administration directly impacts the degree of immune and inflammatory reaction. Subretinal delivery produces a weaker humoral response than the intravitreal route. However, some studies have demonstrated that the subretinal delivery induces a stronger inflammatory reaction. On the other hand, several instances of vision loss due to severe late onset intraocular inflammation were reported in a clinical trial involving intravitreal delivery of viral vectors. When compared with the intravitreal route, suprachoroidal gene delivery has been shown to produce weaker humoral response. However, unlike the subretinal space, the suprachoroidal space is not known to have immune privilege status. Inflammatory reactions following ocular gene therapy are typically mild and most clinical and preclinical studies have shown that they can be controlled with topical, local or systemic steroids. However, severe inflammatory responses may occur and require aggressive management to avoid permanent vision loss. Further investigations are required to elucidate and expand our knowledge of inflammatory reactions, and their optimal management, following ocular gene therapy.

SEQUENTIAL RETINAL THICKNESS ANALYSIS SHOWS HYDROXYCHLOROQUINE DAMAGE BEFORE OTHER SCREENING TECHNIQUES.

PURPOSE: We sought to determine the earliest diagnostic signs of hydroxychloroquine retinopathy up to the point of clinical recognition. METHODS: Retrospective series of 6 patients (5 parafoveal disease; 1 pericentral disease) with at least 3 examinations over 3.5 years or more preceding diagnosis of HCQ retinopathy. Spectral domain optical coherence tomography (sdOCT) cross-sections, fundus autofluorescence (FAF) and visual fields were generated clinically. Stored sdOCT data were re-examined later to generate topographic ellipsoid zone (EZ) maps, minimum intensity (MI) analysis and sequential plots of regional retinal thickness. Retrospective series of six patients (5 parafoveal disease; one pericentral disease) with at least three examinations over 3.5 years or more preceding diagnosis of hydroxychloroquine retinopathy. RESULTS: Spectral domain optical coherence tomography cross-sections and fields showed similar sensitivity; fundus autofluorescence was not helpful. In parafoveal cases, EZ topography and minimum intensity analysis were no more reliable. Sequential thickness plots from four parafoveal cases showed dramatic retinal thinning across the posterior pole beginning 4 years to 5 years before clinical diagnosis, with parafoveal regions thinning even faster. The pericentral case showed thinning only outside the central macula. Peripheral EZ loss was more dramatic with EZ topography than sdOCT cross-sections. CONCLUSION: Sequential retinal thickness plots reveal definitive thinning years before current diagnostic procedures. We hope that OCT manufacturers will develop software to display such measurements. Ellipsoid zone topography was not more sensitive than sdOCT cross-sections, but important for recognizing pericentral disease.

Ultrasound-guided sternoclavicular joint injection: technique and case series.

Sternoclavicular joint pathology can be an uncommon cause of pain and discomfort around the neck and shoulder region. Typically, patients localize their pain deep to the joint and experience referred pain to the ipsilateral neck and shoulder; however, it often presents as a diffuse nonspecific pain. Given the paucity of this pathology and atypical presentation, the use of injections can be helpful to confirm the diagnosis of sternoclavicular arthropathy. Currently, most injections are done via computed tomography. Although this method is accurate, it exposes patients to radiation and burdens the patient with the requirement of multiple appointments. This case series outlines the use of ultrasound-guided sternoclavicular joint injections conducted in the clinic. The patients in this series underwent an ultrasound-guided injection in the affected sternoclavicular joint, which confirmed the diagnosis, and they were subsequently treated with resection arthroplasty. The use of ultrasound-guided injections of the sternoclavicular joint is a safe and accurate alternative diagnostic method, which saves the patient from harmful radiation and additional appointments. Limitations and efficacy may vary depending on skill and comfort level of the operator.

Unilateral acute anterior uveitis with macular edema following the use of sildenafil citrate in a patient with HLA-B27 positivity.

PURPOSE: To present a case of acute anterior uveitis with macular edema associated with sildenafil citrate use in an HLA-B27 positive patient. OBSERVATIONS: A 54-year-old Caucasian male presented at an ophthalmology tertiary center with complaint of pinkish discoloration, irritation, and photophobia in the left eye (OS). He noted that these symptoms appeared one day after using sildenafil for the first time to treat his erectile dysfunction. The patient had no significant ocular history besides refractive surgery in both eyes (OU) and his medical history was insignificant. Best-corrected visual acuity (BCVA) was 20/20 in the right eye (OD) and 20/25 in OS. Slit-lamp-examination (SLE) demonstrated trace cells and 1+ flare in the anterior chamber (AC) in OS and was nonrevealing in AC in OD. Spectral domain optical coherence tomography (SD-OCT) showed parafoveal subretinal hyperreflective deposits in OU. The patient was diagnosed with acute anterior uveitis (AAU) in the left eye and was placed on topical prednisolone acetate.At 2-week follow-up, the patient reported that his eye symptoms had improved since starting topical steroids but worsened again two days after he had used sildenafil for a second time. In OS, best-corrected visual acuity (BCVA) worsened to 20/40, and SLE revealed 1+ cells and 1+ flare in AC. SD-OCT revealed cystoid macular edema only in OS. Fluorescein angiography showed mild staining around the optic disc and significant macular leakage in OS and minimal macular leakage in OD. Uveitis evaluations revealed that the patient was human leukocyte antigen-27 (HLA-B27) positive. The patient was asked to remain off sildenafil and continue topical prednisolone acetate. At 3-month follow-up, BCVA improved to 20/20 in OS with no evidence of active inflammation. CONCLUSIONS AND IMPORTANCE: Sildenafil citrate use might be associated with new onset of intraocular inflammation in predisposed patients. Further studies are necessary to establish this relationship.

Bilateral preretinal hemorrhage associated with Kikuchi-Fujimoto disease.

PURPOSE: To present a case of a patient with human immunodeficiency virus (HIV) disease and Kikuchi-Fujimoto disease (KFD) who presented with a unique pattern of retinopathy. OBSERVATIONS: A 7-year-old Taiwanese girl with HIV disease who was recently diagnosed with KFD had a sudden onset of blurry vision in both eyes one month after her KFD systemic symptoms had relatively resolved. Ophthalmic examination showed decreased visual acuity in both eyes (OU). On fundus examination, she had bilateral preretinal, subhyaloid, and vitreous hemorrhage that was more severe than anemic retinopathy. CONCLUSION: Ocular manifestations in Kikuchi-Fujimoto disease are rare; however, if they occur, presentations may vary. The exact etiology of the disease has remained elusive and controversial. This case is the first report of a patient with HIV disease and KFD presenting with ocular involvement. Furthermore, bilateral preretinal, subhyaloid, and vitreous hemorrhage, which was beyond anemic retinopathy, is an unprecedented manifestation of KFD that has not been previously reported. This case highlights the necessity for clinicians to consider all possible differential diagnoses when evaluating patients with similar findings to identify the best therapeutic approach and avoid unnecessary treatment.

GRHL3 activates FSCN1 to relax cell-cell adhesions between migrating keratinocytes during wound reepithelialization.

The migrating keratinocyte wound front is required for skin wound closure. Despite significant advances in wound healing research, we do not fully understand the molecular mechanisms that orchestrate collective keratinocyte migration. Here, we show that, in the wound front, the epidermal transcription factor Grainyhead like-3 (GRHL3) mediates decreased expression of the adherens junction protein E-cadherin; this results in relaxed adhesions between suprabasal keratinocytes, thus promoting collective cell migration and wound closure. Wound fronts from mice lacking GRHL3 in epithelial cells (Grhl3-cKO) have lower expression of Fascin-1 (FSCN1), a known negative regulator of E-cadherin. Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) on wounded keratinocytes shows decreased wound-induced chromatin accessibility near the Fscn1 gene in Grhl3-cKO mice, a region enriched for GRHL3 motifs. These data reveal a wound-induced GRHL3/FSCN1/E-cadherin pathway that regulates keratinocyte-keratinocyte adhesion during wound-front migration; this pathway is activated in acute human wounds and is altered in diabetic wounds in mice, suggesting translational relevance.

Reperfusion of retinal ischemia in retinal occlusive vasculitis with nicotinic acid and infliximab in Adamantiades-Behçet's disease.

To describe a case of ischemic retinal vasculitis in Adamantiades-Behçet disease (ABD) that demonstrated significant resolution of retinal ischemia following treatment with nicotinic acid and infliximab.Observations: A 12-year-old male with a history of recurrent oral ulcers, fevers, and failure to thrive was admitted to the hospital with fever, oral and perirectal mucositis, and poor oral intake one month before presentation to uveitis clinic. He was suspected to have ABD and was treated with three doses of intravenous (IV) methylprednisolone (30 mg/kg/day) which led to improvement in his systemic symptoms. One week after admission, he complained of decreased vision in both eyes (OU), during which he was found to have anterior uveitis in OU and was referred to the Uveitis Clinic. Upon examination, his visual acuity was 20/80 in OU. Intraocular pressures were within normal limits. Anterior chamber evaluation revealed 0.5+ cells and 1.5+ flare in OU. Posterior examination revealed pale optic nerve, sclerosis and vascular sheathing of retinal arteries, and collateral vessels in OU. Fluorescein angiography (FA) showed optic disc leakage and widespread retinal ischemia in OU. The patient was diagnosed with retinal occlusive vasculitis associated with ABD. He was initially treated with infliximab (5 mg/kg), systemic methylprednisolone, and mycophenolate mofetil. Three months later, his BCVA improved to 20/70 OU with slight improvement of retinal ischemia on FA. Nicotinic acid was added to his treatment regimen. Due to logistic challenges, he did not receive infliximab treatment during the subsequent three months. However, three months after beginning nicotinic acid therapy, FA revealed significant improvement of his retinal ischemia OU. Conclusion: To our knowledge, the index report is the first to show that nicotinic acid may improve retinal ischemia in vaso-occlusive retinal vasculitis and be an integral part of the treatment regimen of this sight-threatening condition.

Anti-interleukin-6 receptor therapy with tocilizumab for refractory pseudophakic cystoid macular edema.

PURPOSE: To describe the clinical course of a patient with refractory pseudophakic cystoid macular edema treated with interleukin-6 receptor antagonist tocilizumab. OBSERVATIONS: An 80-year-old Caucasian man with past ocular history significant for glaucoma (right eye) and iritis presented with cystoid macular edema (CME) in the right eye (OD). His ocular surgery history was significant for cataract extraction with posterior chamber intraocular lenses in 1999 and YAG laser capsulotomy in 2014 in both eyes (OU). His medications at time of presentation included latanoprost and dorzolamide-timolol in OD for glaucoma, as well as prednisolone in OD for iritis. Upon examination, his visual acuity was 20/250 in OD and 20/20 in the left eye (OS). Intraocular pressure was 20 mmHg in OD and 10 mmHg in OS. Slit-lamp examination revealed no cells or flare in OU. Dilated fundus exam showed CME and a cup-to-disk ratio of 0.9 in OD and normal findings in OS. Initial spectral domain optical coherence tomography (SD-OCT) demonstrated intraretinal fluid in both outer and inner layers as well as mild subretinal fluid with an intact ellipsoid zone in OD. Fluorescein angiography revealed perifoveal leakage in OD. Laboratory evaluations, including infectious work-up, were unremarkable. While the patient's CME initially improved after initiation of therapy with topical prednisolone and oral acetazolamide, the CME later recurred after systemic acetazolamide was stopped due to intolerable side effects. Despite multiple therapeutic approaches, including topical and systemic corticosteroids (both oral and intravenous) and topical interferon α2b over the course of more than one year, the patient's visual acuity continued to worsen with increasing intra- and subretinal fluid in the macula. Due to the refractory CME, the patient was started on monthly infusions of anti-interleukin (IL)-6 receptor tocilizumab (8 mg/kg) with three days of methylprednisolone infusions (500 mg/day). After nine cycles of treatment, SD-OCT demonstrated restoration of normal foveal contour with complete resolution of CME. CONCLUSIONS AND IMPORTANCE: IL-6 inhibition with tocilizumab may be a safe and effective treatment for refractory CME. Further studies are needed to elucidate the nature and extent of therapeutic IL-6 inhibition in CME.