Filgotinib in Active Noninfectious Uveitis: The HUMBOLDT Randomized Clinical Trial.

Importance: Noninfectious uveitis is a leading cause of visual impairment with an unmet need for additional treatment options. Objective: To assess the efficacy and safety of filgotinib, a Janus kinase 1 (JAK1) preferential inhibitor, for the treatment of noninfectious uveitis. Design, Setting, and Participants: The HUMBOLDT trial was a double-masked, placebo-controlled, phase 2, randomized clinical trial conducted from July 2017 to April 2021 at 26 centers in 7 countries. Eligible participants (aged ≥18 years) had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite at least 2 weeks of treatment with oral prednisone (10-60 mg per day). Interventions: Participants were randomly assigned 1:1 to receive filgotinib, 200 mg, or placebo orally once daily for up to 52 weeks. Main Outcomes and Measures: The primary end point was the proportion of participants experiencing treatment failure by week 24. Treatment failure was a composite end point represented by assessment of the presence of chorioretinal and/or retinal vascular lesions, best-corrected visual acuity, and anterior chamber cell and vitreous haze grades. Safety was assessed in participants who received at least 1 dose of study drug or placebo. Results: Between July 26, 2017, and April 22, 2021, 116 participants were screened, and 74 (mean [SD] age, 46 [16] years; 43 female [59.7%] of 72 participants, as 2 participants did not receive treatment doses) were randomly assigned to receive filgotinib (n = 38) or placebo (n = 36). Despite early termination of the trial for business reasons ahead of meeting enrollment targets, a significantly reduced proportion of participants who received filgotinib experienced treatment failure by week 24 vs placebo (12 of 32 participants [37.5%] vs 23 of 34 participants [67.6%]; difference vs placebo -30.1%; 95% CI, -56.2% to -4.1%; P = .006). Business reasons were unrelated to efficacy or safety. Adverse events were reported in 30 of 37 participants (81.1%) who received filgotinib and in 24 of 35 participants (68.6%) who received placebo. Serious adverse events were reported in 5 of 37 participants (13.5%) in the filgotinib group and in 2 of 35 participants (5.7%) in the placebo group. No deaths were reported during the trial. Conclusions and Relevance: Results of this randomized clinical trial show that filgotinib lowered the risk of treatment failure in participants with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis vs placebo. Although the HUMBOLDT trial provided evidence supporting the efficacy of filgotinib in patients with active noninfectious uveitis, the premature termination of the trial prevented collection of additional safety or efficacy information of this JAK1 preferential inhibitor. Trial Registration: ClinicalTrials.gov Identifier: NCT03207815.

Managing a patient with uveitis in the era of artificial intelligence: Current approaches, emerging trends, and future perspectives.

The integration of artificial intelligence (AI) with healthcare has opened new avenues for diagnosing, treating, and managing medical conditions with remarkable precision. Uveitis, a diverse group of rare eye conditions characterized by inflammation of the uveal tract, exemplifies the complexities in ophthalmology due to its varied causes, clinical presentations, and responses to treatments. Uveitis, if not managed promptly and effectively, can lead to significant visual impairment. However, its management requires specialized knowledge, which is often lacking, particularly in regions with limited access to health services. AI's capabilities in pattern recognition, data analysis, and predictive modelling offer significant potential to revolutionize uveitis management. AI can classify disease etiologies, analyze multimodal imaging data, predict outcomes, and identify new therapeutic targets. However, transforming these AI models into clinical applications and meeting patient expectations involves overcoming challenges like acquiring extensive, annotated datasets, ensuring algorithmic transparency, and validating these models in real-world settings. This review delves into the complexities of uveitis and the current AI landscape, discussing the development, opportunities, and challenges of AI from theoretical models to bedside application. It also examines the epidemiology of uveitis, the global shortage of uveitis specialists, and the disease's socioeconomic impacts, underlining the critical need for AI-driven approaches. Furthermore, it explores the integration of AI in diagnostic imaging and future directions in ophthalmology, aiming to highlight emerging trends that could transform management of a patient with uveitis and suggesting collaborative efforts to enhance AI applications in clinical practice.

Importance of Baseline Fluorescein Angiography for Patients Presenting to Tertiary Uveitis Clinic.

PURPOSE: To ascertain whether the use of ultra-wide-field fluorescein angiography (UWFFA) at baseline visit alters the assessment of disease activity and localization, as well as the management of patients presenting to a tertiary uveitis clinic. DESIGN: Retrospective comparison of diagnostic approaches. METHODS: Baseline visits of 158 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were evaluated by 3 uveitis-trained ophthalmologists (I.K., A.B., and H.G.). Each eye had undergone clinical examination along with ultra-wide-field fundus photography (UWFFP) (Optos Plc), spectral-domain optical coherence tomography (SD-OCT, Spectralis Heidelberg, Heidelberg Engineering) and UWFFA (Optos Plc) at the baseline visit. Investigators were asked to successively determine disease activity, localization of disease (anterior, posterior or both), and management decisions based on clinical examination and UWFFP and SD-OCT (Set 1) and Set 1 plus UWFFA (Set 2). The primary outcome was the percentage of eyes whose management changed based on the availability of UWFFA compared with Set 1. RESULTS: The mean age of the patients was 46.9 ± 22.4 years (range, 7-96), and 91 (57.6%) were female. With Set 1 alone, 138 eyes (55.2%) were found to have active disease; localization was anterior in 58 eyes (42.0%), posterior in 53 eyes (38.4%), and anterior + posterior in 27 eyes (19.6%). With Set 2, 169 eyes of 107 patients had active anterior, posterior, or panuveitis. In comparison with Set 1, assessment with Set 2 identified additional 31 eyes (18.3%) with active disease (P = .006) and an additional 31 eyes (18.3%) having disease in both anterior + posterior segments (P < .001). Regarding the primary outcome, management was changed in 68 eyes (27.4%) in Set 2 compared with Set 1. CONCLUSIONS: Baseline UWFFA may alter assessment of disease activity, localization, and management decisions compared with clinical examination with only UWFFP and SD-OCT for eyes with uveitis. Thus, UWFFA may be considered as an essential tool in the evaluation of patients with uveitis at the baseline visit.

A User-friendly Approach for the Diagnosis of Diabetic Retinopathy Using ChatGPT and Automated Machine Learning.

Purpose: To assess the capabilities of Chat Generative Pre-trained Transformer (ChatGPT) and Vertex AI in executing code-free preprocessing, training machine learning (ML) models, and analyzing the data. Design: Evaluation of diagnostic test or technology. Participants: ChatGPT and Vetrex AI as publicly available large language model and ML platform, respectively. Methods: ChatGPT was employed to improve the resolution of fundus photography images from the Methods to Evaluate Segmentation and Indexing Techniques in the field of Retinal Ophthalmology (Messidor-2) open-source dataset using the Contrast Limited Adaptive Histogram Equalization (CLAHE) technique by Fiji software. Subsequently, Vertex AI, an automated ML (AutoML) platform, was utilized to develop 2 classification models. The first model served as a binary classifier for detecting the presence of diabetic retinopathy (DR), while the second determined its severity. Finally, ChatGPT was used to provide scripts for R and Python programming languages for data analysis and was also directly employed in analyzing the data in a code-free method. Main Outcome Measures: Evaluating the utility of ChatGPT in generating scripts for preprocessing images using Fiji and analyzing data across Python and R and assessing its potential in analyzing data through a code-free method. Investigating the capabilities of Vertex AI to train image classification models for detection of DR and its severity. Results: Two ML models were trained using 1740 images from the Messidor-2 database. The first model, designed to detect the severity of DR, achieved an area under the precision-recall curve (AUPRC) of 0.81, with a precision rate of 81.81% and recall of 72.83%. The second model, tailored for the detection of the presence of DR, recorded a precision and recall of 84.48% with an AUPRC of 0.90. Conclusions: ChatGPT and Vertex AI have the potential to enable physicians without coding expertise to preprocess images, analyze data, and train ML models. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Risk factors for development of anti-adalimumab antibodies in non-infectious uveitis.

Purpose: To evaluate risk factors associated with development of anti-adalimumab antibodies (AAA) in patients with non-infectious uveitis treated with adalimumab. Methods: A retrospective, cross-sectional, case-control study was done evaluating patients with non-infectious uveitis treated with adalimumab for at least 12 months and have undergone testing for AAA levels. Demographics, clinical characteristics, grading of ocular inflammation, and previous and concomitant immunomodulatory therapy were assessed. Univariate and multivariate analysis were done to estimate odds ratio (OR) with 95% confidence intervals for the various risk factors. Results: A total of 31 patients were included in the analysis, in which 12 patients who tested positive (Group 1) were matched with 19 patients who tested negative for AAA (Group 2). The groups differed significantly in terms of sex (female) (91.7% vs 52.6%, p = 0.046), presence of systemic disease (91.7% vs 42.1%, p = 0.008), and presence of anterior chamber inflammation at baseline (100% vs 63.2%, p = 0.026). A history of interruption in anti-TNF therapy prior to starting or restarting adalimumab was found to have an increased odds for development of AAA (OR 16.89 [2.92, 107.11], p = 0.008), as well as flare-ups (reactivation of disease) during adalimumab therapy (OR 6.77 [1.80, 61.80], p = 0.027). Weekly dosing of adalimumab was shown to decrease odds of AAA development (OR 0.34 [0.02, 0.70], p = 0.040), while concomitant anti-metabolite therapy was not shown to be a statistically significant protective factor (OR 2.22 [0.50, 9.96], p = 0.148). Conclusions: History of interruption in anti-TNF therapy and flare during adalimumab were associated with development of AAA, while weekly dosing of adalimumab was protective against AAA. Identification of those with higher risk of developing AAA may guide in clinical decision making to optimize management for these patients.

Biosimilars of anti-vascular endothelial growth factor for ophthalmic diseases: A review.

The development of intravitreally injected biologic medicines (biologics) acting against vascular endothelial growth factor (VEGF) substantially improved the clinical outcomes of patients with common VEGF-driven retinal diseases. The relatively high cost of branded agents, however, represents a financial burden for most healthcare systems and patients, likely resulting in impaired access to treatment and poorer clinical outcomes for some patients. Biosimilar medicines (biosimilars) are clinically equivalent, potentially economic alternatives to reference products. Biosimilars approved by leading health authorities have been demonstrated to be similar to the reference product in a comprehensive comparability exercise, generating the totality of evidence necessary to support analytical, pre-clinical, and clinical biosimilarity. Anti-VEGF biosimilars have been entering the field of ophthalmology in the US since 2022. We review regulatory and scientific concepts of biosimilars, the biosimilar development landscape in ophthalmology, with a specific focus on anti-VEGF biosimilars, and discuss opportunities and challenges facing the uptake of biosimilars.

Intravenous cyclophosphamide therapy for patients with severe ocular inflammatory diseases who failed other immunomodulatory therapies.

BACKGROUND: Ocular inflammatory diseases, including scleritis and uveitis, have been widely treated with immunomodulatory therapies (IMTs) as a steroid-sparing approach. Such strategy includes conventional therapies (antimetabolites, alkylating agents, and calcineurin inhibitors) as well as biologic agents like adalimumab, infliximab, rituximab, and tocilizumab. Cyclophosphamide (CP) is an alkylating agent and mainly inhibits the functioning of both T and B cells. Though known to have potential adverse events, including bone marrow suppression, hemorrhagic cystitis, and sterility, CP has been shown to be efficacious, especially in recalcitrant cases and when used intravenous (IV) for a limited period. MAIN FINDINGS: We conducted a retrospective case-series to assess the safety and efficacy of CP therapy for patients with severe ocular inflammatory diseases who failed other IMTs. Medical records of 1295 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were reviewed. Seven patients (10 eyes) who received CP therapy for ocular inflammatory diseases with at least one year of follow-up were included. The mean age of the patients (4 males, 3 females) was 61.6 ± 14.9 (43.0-89.0) years. Clinical diagnoses included necrotizing scleritis (5 eyes), peripheral ulcerative keratitis (2 eyes), orbital pseudotumor (1 eye), HLA-B27 associated panuveitis and retinal vasculitis (2 eyes). Ocular disease was idiopathic in 3 patients, and was associated with rheumatoid arthritis, IgG-4 sclerosing disease, dermatomyositis, and ankylosing spondylitis in 1 patient each. All the patients had history of previous IMT use including methotrexate (5), mycophenolate mofetil (3), azathioprine (1), tacrolimus (1), adalimumab (2), infliximab (4), and rituximab (1). The mean follow-up time was 34.4 ± 11.0 (13-45) months, and mean duration of CP therapy was 11.9 ± 8.8 (5-28) months. Remission was achieved in 5 patients (71.4%). Four patients (57.1%) experienced transient leukopenia (white blood cell count < 4000/mL). SHORT CONCLUSION: CP therapy can be considered a potentially effective and relatively safe therapeutic option for patients with severe ocular inflammatory diseases who failed other IMTs including biologics (TNFa and CD20 inhibitors).

Giant bile duct dilatation in newborn: A case report.

BACKGROUND: Giant congenital biliary dilation (CBD) is a rare condition observed in clinical practice. Infants born with this condition often experience a poor overall health status, and the disease progresses rapidly, leading to severe biliary obstruction, infections, pressure exerted by the enlarged CBD on abdominal organs, disturbances in the internal environment, and multiple organ dysfunction. The treatment of giant CBD using laparoscopy is challenging due to the high degree of variation in the shape of the bile duct and other organs, making it difficult to separate the bile duct wall from adjacent tissues or to control bleeding. CASE SUMMARY: Herein, we present the details of an 11-d-old male newborn who was diagnosed with giant CBD. The patient was admitted to the neonatal surgery department of our hospital due to a history of common bile duct cyst that was detected more than 3 mo ago, and also because the patient had been experiencing yellowish skin for the past 9 d. The abnormal echo in the fetal abdomen was first noticed by the patient's mother during a routine ultrasound examination at a local hospital, when the patient was at 24 wk + 6 d of pregnancy. This finding raised concerns about the possibility of congenital biliary dilatation (22 mm × 21 mm). Subsequent ultrasound examinations at different hospitals consistently confirmed the presence of a congenital biliary dilatation. No specific treatment was administered for biliary dilatation during this period. A computed tomography scan conducted during the hospitalization revealed a large cystic mass in the right upper quadrant and pelvis, measuring approximately 9.2 cm × 7.4 cm × 11.3 cm. Based on the scan, it was classified as a type I biliary dilatation. CONCLUSION: The analysis reveals that prenatal imaging techniques, such as ultrasound and magnetic resonance imaging, play a crucial role in the early diagnosis, fetal prognosis, and treatment plan for giant CBD. Laparoscopic surgery for giant CBD presents certain challenges, including difficulties in separating the cyst wall, anastomosis, and hemostasis, as well as severe biliary system infection and ulceration. Consequently, there is a high likelihood of converting to laparotomy. The choice between surgical methods like hepaticojejunostomy (HJ) or hepaticoduodenostomy has not been standardized yet. However, we have achieved favorable outcomes using HJ. Preoperative management of inflammation, biliary drainage, liver function protection, and supportive treatment are particularly vital in improving children's prognosis. After discharge, it is essential to conduct timely reexamination and close follow-up to identify potential complications.

Challenges for further successful development of tumor necrosis factor targeting therapies for uveitis.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU. AREAS COVERED: The index article summarizes the present experience of anti-TNF-α agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-α agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-α drug development, and promising competitor drug candidates are discussed and evaluated. EXPERT OPINION: Anti-TNF-α agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-α agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-α drug development.

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.

Ocular syphilis masquerading as refractory retinal diseases.

PURPOSE: To report two cases of syphilis masquerading as chronic refractory macular diseases. CASE DESCRIPTIONS: Two patients had been diagnosed with neovascular age-related macular degeneration (neovascular AMD) and diabetic macular edema (DME), respectively. The disease worsened despite repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) and also surgical treatment (in suspected case of DME). Systemic evaluations were positive for syphilis. Intravenous penicillin was started, and the macular diseases improved. The lesions were well controlled afterward. CONCLUSIONS: The current two cases demonstrated that ocular syphilis can masquerade as refractory chronic retinal diseases such as DME and neovascular AMD. Laboratory evaluations for syphilis may be needed, not only for uveitis but also for refractory retinal diseases. Indocyanine green angiography may be helpful to reveal occult syphilis.

Cytomegalovirus Corneal Endotheliitis: A Comprehensive Review.

Cytomegalovirus (CMV) anterior uveitis and corneal endotheliitis are the most common ocular diseases caused by CMV infections in immunocompetent patients. The incidence of CMV corneal endotheliitis is relatively high in middle-aged men. CMV corneal endotheliitis presents with mild anterior chamber inflammation, corneal edema, keratic precipitates, and elevated intraocular pressure. It resembles Posner-Schlossman syndrome and Fuchs uveitis because of the elevated intraocular pressure. Without proper diagnosis and treatment, it may progress to bullous keratopathy or glaucoma, necessitating keratoplasty or glaucoma surgery. Therefore, early diagnosis and treatment are important for a good prognosis. Aqueous humor analysis can facilitate the diagnosis of CMV corneal endotheliitis, and early antiviral treatment can decrease the risk of corneal compensation or glaucomatous optic atrophy. In this article, we review the epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of CMV corneal endotheliitis along with the evidence for early clinical diagnosis and active antiviral treatment.

Ocular manifestations and clinical outcomes in Tubulointerstitial Nephritis and Uveitis Syndrome (TINU).

PURPOSE: To describe the various ocular clinical features and visual outcomes in Tubulointerstitial Nephritis and Uveitis Syndrome (TINU). METHODS: The medical records of 13 patients (26 eyes) diagnosed with TINU were reviewed. RESULTS: Twenty-six (26) eyes of 13 patients with TINU were reviewed in this study. The median age at onset of uveitis was 14 (range, 9-45). Eight (61.5%) subjects were female. The median follow-up of patients was 30 months (range, 6-89 months). Posterior segment findings were seen in 18 eyes of 9 patients (69.2%). The most common posterior findings were optic nerve head inflammation (16 eyes, 88.8%) and retinal vasculitis (13 eyes, 72.2%). Other posterior findings included vitritis (8 eyes, 44.4%), macular edema (6 eyes, 33.3%), snowball (4 eyes, 22.2%), and chorioretinal lesions (2 eye, 11.1%). Eight patients had fluorescein angiography (FA) data available and most eyes had retinal capillary leakage (13 eyes, 81.2%) followed by optic disc staining/leakage (12 eyes, 75%). Twelve (12) patients (92.3%) were treated with immunomodulatory treatment (IMT) and/or biologics. Five patients (%38.4) required biologics to control intraocular inflammation. CONCLUSION: Posterior segment involvement may be common in patients with TINU syndrome. FA provides significant information for detecting posterior segment involvement and disease activity in TINU. The majority of patients required systemic treatment in order to control intraocular inflammation and prevent relapses.

The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 1-global current practice patterns for the management of Herpes Simplex Virus and Varicella Zoster Virus anterior uveitis.

AIMS: To present current expert practice patterns and to formulate a consensus for the management of HSV and VZV AU by uveitis specialists worldwide. METHODS: A two-round online modified Delphi survey with masking of the study team was conducted. Responses were collected from 76 international uveitis experts from 21 countries. Current practices in the diagnosis and treatment of HSV and VZV AU were identified. A working group (The Infectious Uveitis Treatment Algorithm Network [TITAN]) developed data into consensus guidelines. Consensus is defined as a particular response towards a specific question meeting ≥75% of agreement or IQR ≤ 1 when a Likert scale is used. RESULTS: Unilaterality, increased intraocular pressure (IOP), decreased corneal sensation and diffuse or sectoral iris atrophy are quite specific for HSV or VZV AU from consensus opinion. Sectoral iris atrophy is characteristic of HSV AU. Treatment initiation is highly variable, but most experts preferred valacyclovir owing to simpler dosing. Topical corticosteroids and beta-blockers should be used if necessary. Resolution of inflammation and normalisation of IOP are clinical endpoints. CONCLUSIONS: Consensus was reached on several aspects of diagnosis, choice of initial treatment, and treatment endpoints for HSV and VZV AU. Treatment duration and management of recurrences varied between experts.

The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 2-global current practice patterns for the management of Cytomegalovirus anterior uveitis.

AIMS: To present current practice patterns in the diagnosis and management of Cytomegalovirus anterior uveitis (CMV AU) by uveitis experts worldwide. METHODS: A two-round modified Delphi survey with masking of the study team was performed. Based on experience and expertise, 100 international uveitis specialists from 21 countries were invited to participate in the survey. Variation in the diagnostic approaches and preferred management of CMV AU was captured using an online survey platform. RESULTS: Seventy-five experts completed both surveys. Fifty-five of the 75 experts (73.3%) would always perform diagnostic aqueous tap in suspected CMV AU cases. Consensus was achieved for starting topical antiviral treatment (85% of experts). About half of the experts (48%) would only commence systemic antiviral treatment for severe, prolonged, or atypical presentation. The preferred specific route was ganciclovir gel 0.15% for topical treatment (selected by 70% of experts) and oral valganciclovir for systemic treatment (78% of experts). The majority of experts (77%) would commence treatment with topical corticosteroid four times daily for one to two weeks along with antiviral coverage, with subsequent adjustment depending on the clinical response. Prednisolone acetate 1% was the drug of choice (opted by 70% of experts). Long-term maintenance treatment (up to 12 months) can be considered for chronic course of inflammation (88% of experts) and those with at least 2 episodes of CMV AU within a year (75-88% of experts). CONCLUSIONS: Preferred management practices for CMV AU vary widely. Further research is necessary to refine diagnosis and management and provide higher-level evidence.

Fundus topographical distribution patterns of ocular toxoplasmosis.

BACKGROUND: To establish topographic maps and determine fundus distribution patterns of ocular toxoplasmosis (OT) lesions. METHODS: In this retrospective study, patients who presented with OT to ophthalmology clinics from four countries (Argentina, Turkey, UK, USA) were included. Size, shape and location of primary (1°)/recurrent (2°) and active/inactive lesions were converted into a two-dimensional retinal chart by a retinal drawing software. A final contour map of the merged image charts was then created using a custom Matlab programme. Descriptive analyses were performed. RESULTS: 984 lesions in 514 eyes of 464 subjects (53% women) were included. Mean area of all 1° and 2° lesions was 5.96±12.26 and 5.21±12.77 mm2, respectively. For the subset group lesions (eyes with both 1° and 2° lesions), 1° lesions were significantly larger than 2° lesions (5.52±6.04 mm2 vs 4.09±8.90 mm2, p=0.038). Mean distances from foveola to 1° and 2° lesion centres were 6336±4267 and 5763±3491 µm, respectively. The majority of lesions were found in temporal quadrant (p<0.001). Maximum overlap of all lesions was at 278 µm inferotemporal to foveola. CONCLUSION: The 1° lesions were larger than 2° lesions. The 2° lesions were not significantly closer to fovea than 1° lesions. Temporal quadrant and macular region were found to be densely affected underlining the vision threatening nature of the disease.

Exploring the role of retinal fluid as a biomarker for the management of diabetic macular oedema.

Anti-VEGF therapies are associated with significant gains in visual acuity and fluid resolution in the treatment of diabetic macular oedema (DMO) and have become the standard of care. However, despite their efficacy, outcomes can be unpredictable, vary widely between individual eyes, and a large proportion of patients have persistent fluid following initial treatment, with a negative impact on visual outcomes. Anatomical parameters measured by optical coherence tomography (OCT), in addition to visual acuity, are key to monitoring treatment effectiveness and guiding retreatment decisions; however, existing guidelines on the management of DMO lack clear recommendations for interpretation of OCT parameters, or proposed thresholds of various markers to guide retreatment decisions. Although central subfield thickness (CSFT) has been widely used as a marker for retreatment decisions in clinical trials in DMO, and a reduction in CSFT has generally been shown to accompany improvements in best-corrected visual acuity with treatment, analyses of the relationship between these parameters show that the correlation is small to moderate. A more direct relationship can be seen between an increased magnitude of CSFT fluctuations over time and poorer visual acuity, suggesting that control of CSFT could be important in maximising visual outcomes. The relationship between visual outcomes and qualitatively assessed intraretinal fluid and subretinal fluid is also unclear, although quantitative assessments of fluid parameters suggest that untreated intraretinal fluid and subretinal fluid negatively impact visual outcomes. These findings highlight a need for clearer guidelines on the management of retinal fluid to improve visual outcomes for patients with DMO.

Ocular Ischemic Syndrome in the Setting of Normal Carotid Duplex Ultrasound.

PURPOSE: To describe two cases of ocular ischemic syndrome (OIS) that were initially ruled out due to a negative carotid duplex ultrasound (DUS) but eventually confirmed by angiography studies. METHODS: Case series. RESULTS: Case 1: A 67-year-old female presented with symptoms suggestive of OIS, but carotid DUS was negative, and the patient was diagnosed with occlusive retinal vasculitis due to retinal non-perfusion and vascular leakage on fluorescein angiography (FA). Immunosuppressive therapy was initiated but her symptoms did not improve. Computerized tomography angiography (CTA) was significant for severe osteal stenosis of the aortic arch vessels. Left common carotid angioplasty and stenting resulted in complete resolution of the symptoms and vascular leakage of the left eye. Case 2: A 41-year-old male with cryoglobulinemia-associated vasculitis complained of symptoms consistent with OIS, which was initially ruled out through a negative carotid DUS. FA revealed delayed arterial filling with poor retinal perfusion. Magnetic resonance angiography (MRA) revealed ophthalmic artery stenosis which was attributed to the underlying systemic vasculitis. CONCLUSION: CTA or MRA should be performed to rule out OIS if DUS is negative in the setting of high clinical suspicion. Carotid ostial and ophthalmic artery stenoses are rare but possible causes of OIS.