Aqueous humour interleukin-6 and vision outcomes with anti-vascular endothelial growth factor therapy.

BACKGROUND: This analysis evaluated aqueous humour (AH) interleukin (IL)-6 concentrations and the association between AH IL-6 and visual outcomes in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DMO) receiving anti-vascular endothelial growth factor (VEGF) monotherapy. METHODS: Post hoc analysis of the multicentre, double-masked, randomised HARBOR (NCT00891735) and READ-3 (NCT01077401) trials. HARBOR enrolled treatment-naïve nAMD patients. READ-3 enrolled treatment-naïve/previously treated DMO patients. HARBOR patients received ranibizumab 0.5 or 2.0 mg monthly or as needed; AH samples were collected at month 2, after two previous intravitreal injections. READ-3 patients received ranibizumab 0.5 or 2.0 mg as needed; AH samples were collected at baseline and months 3, 6, 9, and 12. MAIN OUTCOME MEASURE: association between AH IL-6 concentrations and month 24 best-corrected visual acuity (BCVA). RESULTS: In both trials (HARBOR, N = 36; READ-3, N = 137), patients with higher AH IL-6 concentrations had worse visual outcomes. HARBOR patients with low AH IL-6 concentrations at month 2 had a mean (95% CI) BCVA change at month 24 of +2.9 (-2.6, 8.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of -9.0 (-22.7, 4.7) letters. READ-3 patients with low AH concentrations at baseline had a mean (95% CI) BCVA change at month 12 of +9.3 (7.4, 11.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of +5.6 (2.2, 9.1) letters. CONCLUSIONS: Higher IL-6 AH concentrations may predict suboptimal visual responses to anti-VEGF monotherapy in patients with nAMD/DMO.

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.

Intravitreal aflibercept 8 mg in diabetic macular oedema (PHOTON): 48-week results from a randomised, double-masked, non-inferiority, phase 2/3 trial.

BACKGROUND: A high-dose formulation of intravitreal aflibercept (8 mg) could improve treatment outcomes in diabetic macular oedema (DMO) by requiring fewer injections than the standard comparator, aflibercept 2 mg. We report efficacy and safety results of aflibercept 8 mg versus 2 mg in patients with DMO. METHODS: PHOTON was a randomised, double-masked, non-inferiority, phase 2/3 trial performed at 138 hospitals and specialty retina clinics in seven countries. Eligible patients were adults aged 18 years or older with type 1 or 2 diabetes and centre-involved DMO. Patients were randomly assigned (1:2:1) to intravitreal aflibercept 2 mg every 8 weeks (2q8), aflibercept 8 mg every 12 weeks (8q12), or aflibercept 8 mg every 16 weeks (8q16), following initial monthly dosing. From week 16, dosing intervals for the aflibercept 8 mg groups were shortened if patients met prespecified dose regimen modification criteria denoting disease activity. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48 (non-inferiority margin of 4 letters). Efficacy and safety analyses included all randomly assigned patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT04429503). FINDINGS: Between June 29, 2020, and June 28, 2021, 970 patients were screened for eligibility. After exclusions, 660 patients were enrolled and randomly assigned to receive aflibercept 8q12 (n=329), 8q16 (n=164), or 2q8 (n=167); two patients were randomly assigned in error and did not receive treatment. 658 (99·7%) patients were treated and included in the full analysis set and safety analysis set (8q12 n=328, 8q16 n=163, and 2q8 n=167). Mean patient age was 62·3 years (SD 10·4). 401 (61%) patients were male. 471 (72%) patients were White. Aflibercept 8q12 and 8q16 demonstrated non-inferior BCVA gains to aflibercept 2q8 (BCVA mean change from baseline 8·8 letters [SD 9·0] in the 8q12 group, 7·9 letters [8·4] in the 8q16 group, and 9·2 letters [9·0] in the 2q8 group). The difference in least squares means was -0·57 letters (95% CI -2·26 to 1·13, p value for non-inferiority <0·0001) between 8q12 and 2q8 and -1·44 letters (-3·27 to 0·39, p value for non-inferiority 0·0031) between aflibercept 8q16 and 2q8. Proportions of patients with ocular adverse events in the study eye were similar across groups (8q12 n=104 [32%], 8q16 n=48 [29%], and 2q8 n=46 [28%]). INTERPRETATION: Aflibercept 8 mg demonstrated efficacy and safety with extended dosing intervals and could decrease treatment burden in patients with DMO. FUNDING: Regeneron Pharmaceuticals and Bayer.

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).

Dr. Google vs. Dr. ChatGPT: Exploring the Use of Artificial Intelligence in Ophthalmology by Comparing the Accuracy, Safety, and Readability of Responses to Frequently Asked Patient Questions Regarding Cataracts and Cataract Surgery.

PURPOSE: Patients are using online search modalities to learn about their eye health. While Google remains the most popular search engine, the use of large language models (LLMs) like ChatGPT has increased. Cataract surgery is the most common surgical procedure in the US, and there is limited data on the quality of online information that populates after searches related to cataract surgery on search engines such as Google and LLM platforms such as ChatGPT. We identified the most common patient frequently asked questions (FAQs) about cataracts and cataract surgery and evaluated the accuracy, safety, and readability of the answers to these questions provided by both Google and ChatGPT. We demonstrated the utility of ChatGPT in writing notes and creating patient education materials. METHODS: The top 20 FAQs related to cataracts and cataract surgery were recorded from Google. Responses to the questions provided by Google and ChatGPT were evaluated by a panel of ophthalmologists for accuracy and safety. Evaluators were also asked to distinguish between Google and LLM chatbot answers. Five validated readability indices were used to assess the readability of responses. ChatGPT was instructed to generate operative notes, post-operative instructions, and customizable patient education materials according to specific readability criteria. RESULTS: Responses to 20 patient FAQs generated by ChatGPT were significantly longer and written at a higher reading level than responses provided by Google (p < .001), with an average grade level of 14.8 (college level). Expert reviewers were correctly able to distinguish between a human-reviewed and chatbot generated response an average of 31% of the time. Google answers contained incorrect or inappropriate material 27% of the time, compared with 6% of LLM generated answers (p < .001). When expert reviewers were asked to compare the responses directly, chatbot responses were favored (66%). CONCLUSIONS: When comparing the responses to patients' cataract FAQs provided by ChatGPT and Google, practicing ophthalmologists overwhelming preferred ChatGPT responses. LLM chatbot responses were less likely to contain inaccurate information. ChatGPT represents a viable information source for eye health for patients with higher health literacy. ChatGPT may also be used by ophthalmologists to create customizable patient education materials for patients with varying health literacy.

LIGHTSITE III: 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the Lumithera Valeda Light Delivery System.

PURPOSE: The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) age-related macular degeneration (AMD) using the LumiThera Valeda Light Delivery System. METHODS: LIGHTSITE III is a randomized, controlled trial to assess the safety and effectiveness of PBM in dry AMD. Subjects were given multiwavelength PBM (590, 660, and 850 nm) or Sham treatment delivered in a series of nine sessions over 3 to 5 weeks every four months over 24 months. Subjects were assessed for efficacy and safety outcomes. Data from the 13-month analysis are presented in this report. RESULTS: A total of 100 subjects (148 eyes) with dry AMD were randomized. LIGHTSITE III met the primary efficacy best-corrected visual acuity endpoint with a significant difference between PBM (n = 91 eyes) and Sham (n = 54 eyes) groups (Between group difference: 2.4 letters (SE 1.15), CI: -4.7 to -0.1, P = 0.02) (PBM alone: 5.4 letters (SE 0.96), CI: 3.5 to 7.3, P < 0.0001; Sham alone: 3.0 letters (SE 1.13), CI: 0.7-5.2, P < 0.0001). The PBM group showed a significant decrease in new onset geographic atrophy ( P = 0.024, Fisher exact test, odds ratio 9.4). A favorable safety profile was observed. CONCLUSION: LIGHTSITE III provides a prospective, randomized, controlled trial showing improved clinical and anatomical outcomes in intermediate dry AMD following PBM therapy.

Structural and Functional Changes in Non-Paraneoplastic Autoimmune Retinopathy.

BACKGROUND: To describe longitudinal changes in patients with non-paraneoplastic autoimmune retinopathy (npAIR) by utilizing different diagnostic modalities/tests. METHODS: The index study is a retrospective longitudinal review of sixteen eyes of eight patients from a tertiary care eye hospital diagnosed with npAIR. Multiple diagnostic modalities such as wide-angle fundus photography (WAFP), WA fundus autofluorescence (WAFAF), spectral-domain optical coherence tomography (SD-OCT), Goldmann visual field (GVF) perimetry, microperimetry (MP), electrophysiologic testing, and adaptive optics scanning laser ophthalmoscopy (AOSLO) were reviewed and analyzed. RESULTS: At the baseline visits, anomalies were detected by multimodal diagnostic tests on all patients. Subjects were followed up for a median duration of 11.5 [3.0-18.7] months. Structural changes at the baseline were detected in 14 of 16 (87.5%) eyes on WAFP and WAFAF and 13 of 16 (81.2%) eyes on SD-OCT. Eight of the ten (80%) eyes that underwent AOSLO imaging depicted structural changes. Functional changes were detected in 14 of 16 (87.5%) eyes on GVF, 15 of 16 (93.7%) eyes on MP, and 11 of 16 (68.7%) eyes on full-field electroretinogram (ff-ERG). Multifocal electroretinogram (mf-ERG) and visual evoked potential (VEP) tests were performed in 14 eyes, of which 12 (85.7%) and 14 (100%) of the eyes demonstrated functional abnormalities, respectively, at baseline. Compared to all the other structural diagnostic tools, AOSLO had a better ability to demonstrate deterioration in retinal microstructures occurring at follow-ups. Functional deterioration at follow-up was detected on GVF in 8 of 10 (80%) eyes, mf-ERG in 4 of 8 (50%) eyes, and MP in 7 of 16 (43.7%) eyes. The ff-ERG and VEP were stable in the majority of cases at follow-up. CONCLUSIONS: The utilization of multimodal imaging/tests in the diagnosing and monitoring of npAIR patients can aid in identifying anomalous changes over time. Analysis of both the anatomical and functional aspects by these devices can be supportive of detecting the changes early in such patients. AOSLO shows promise as it enables the capture of high-resolution images demonstrating quantifiable changes to retinal microstructure.

Anterior segment ischemia following strabismus surgery in a young adult using gender-affirming estrogen hormone therapy.

Well-known risk factors for anterior segment ischemia (ASI) following strabismus surgery include ipsilateral surgery on three or more rectus muscles, older age, and vasculopathy. ASI is rarely reported in young patients following uneventful strabismus surgery on two ipsilateral rectus muscles. We report a 30-year-old transgender female on long-term estrogen therapy who underwent strabismus surgery involving recessions of both lateral rectus muscles, the right inferior rectus muscle, and the left superior rectus muscle. The left eye developed severe ASI with hypotony maculopathy that was resistant to topical medications, oral steroids, anterior chamber reformation, and intravitreal steroid injection. Following phacoemulsification with intraocular lens and capsular tension ring insertion 1 year later, intraocular pressure and hypotony maculopathy improved.

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.

Blood pressure control for diabetic retinopathy.

BACKGROUND: Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood glucose control to prevent development and progression of the ocular complications of diabetes. Concurrent blood pressure control has been advocated for this purpose, but individual studies have reported varying conclusions regarding the effects of this intervention. OBJECTIVES: To summarize the existing evidence regarding the effect of interventions to control blood pressure levels among diabetics on incidence and progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs. SEARCH METHODS: We searched several electronic databases, including CENTRAL, and trial registries. We last searched the electronic databases on 3 September 2021. We also reviewed the reference lists of review articles and trial reports selected for inclusion. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which either type 1 or type 2 diabetic participants, with or without hypertension, were assigned randomly to more intense versus less intense blood pressure control; to blood pressure control versus usual care or no intervention on blood pressure (placebo); or to one class of antihypertensive medication versus another or placebo. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently reviewed the titles and abstracts of records identified by the electronic and manual searches and the full-text reports of any records identified as potentially relevant. The included trials were independently assessed for risk of bias with respect to outcomes reported in this review. MAIN RESULTS: We included 29 RCTs conducted in North America, Europe, Australia, Asia, Africa, and the Middle East that had enrolled a total of 4620 type 1 and 22,565 type 2 diabetic participants (sample sizes from 16 to 4477 participants). In all 7 RCTs for normotensive type 1 diabetic participants, 8 of 12 RCTs with normotensive type 2 diabetic participants, and 5 of 10 RCTs with hypertensive type 2 diabetic participants, one group was assigned to one or more antihypertensive agents and the control group to placebo. In the remaining 4 RCTs for normotensive participants with type 2 diabetes and 5 RCTs for hypertensive type 2 diabetic participants, methods of intense blood pressure control were compared to usual care. Eight trials were sponsored entirely and 10 trials partially by pharmaceutical companies; nine studies received support from other sources; and two studies did not report funding source. Study designs, populations, interventions, lengths of follow-up (range less than one year to nine years), and blood pressure targets varied among the included trials. For primary review outcomes after five years of treatment and follow-up, one of the seven trials for type 1 diabetics reported incidence of retinopathy and one trial reported progression of retinopathy; one trial reported a combined outcome of incidence and progression (as defined by study authors). Among normotensive type 2 diabetics, four of 12 trials reported incidence of diabetic retinopathy and two trials reported progression of retinopathy; two trials reported combined incidence and progression. Among hypertensive type 2 diabetics, six of the 10 trials reported incidence of diabetic retinopathy and two trials reported progression of retinopathy; five of the 10 trials reported combined incidence and progression. The evidence supports an overall benefit of more intensive blood pressure intervention for five-year incidence of diabetic retinopathy (11 studies; 4940 participants; risk ratio (RR) 0.82, 95% confidence interval (CI) 0.73 to 0.92; I2 = 15%; moderate certainty evidence) and the combined outcome of incidence and progression (8 studies; 6212 participants; RR 0.78, 95% CI 0.68 to 0.89; I2 = 42%; low certainty evidence). The available evidence did not support a benefit regarding five-year progression of diabetic retinopathy (5 studies; 5144 participants; RR 0.94, 95% CI 0.78 to 1.12; I2 = 57%; moderate certainty evidence), incidence of proliferative diabetic retinopathy, clinically significant macular edema, or vitreous hemorrhage (9 studies; 8237 participants; RR 0.92, 95% CI 0.82 to 1.04; I2 = 31%; low certainty evidence), or loss of 3 or more lines on a visual acuity chart with a logMAR scale (2 studies; 2326 participants; RR 1.15, 95% CI 0.63 to 2.08; I2 = 90%; very low certainty evidence). Hypertensive type 2 diabetic participants realized more benefit from intense blood pressure control for three of the four outcomes concerning incidence and progression of diabetic retinopathy. The adverse event reported most often (13 of 29 trials) was death, yielding an estimated RR 0.87 (95% CI 0.76 to 1.00; 13 studies; 13,979 participants; I2 = 0%; moderate certainty evidence). Hypotension was reported in two trials, with an RR of 2.04 (95% CI 1.63 to 2.55; 2 studies; 3323 participants; I2 = 37%; low certainty evidence), indicating an excess of hypotensive events among participants assigned to more intervention on blood pressure. AUTHORS' CONCLUSIONS: Hypertension is a well-known risk factor for several chronic conditions for which lowering blood pressure has proven to be beneficial. The available evidence supports a modest beneficial effect of intervention to reduce blood pressure with respect to preventing diabetic retinopathy for up to five years, particularly for hypertensive type 2 diabetics. However, there was a paucity of evidence to support such intervention to slow progression of diabetic retinopathy or to affect other outcomes considered in this review among normotensive diabetics. This weakens any conclusion regarding an overall benefit of intervening on blood pressure in diabetic patients without hypertension for the sole purpose of preventing diabetic retinopathy or avoiding the need for treatment for advanced stages of diabetic retinopathy.

Birdshot chorioretinopathy in an HLA-A29 positive Asian patient.

Purpose: To present a case of birdshot chorioretinopathy (BCR) in a Chinese patient with HLA-A29 positivity. Observations: A 45-year-old Chinese female presented at a tertiary Ophthalmology Clinic with complaints of frequent headaches as well as blurred vision, photophobia, and pressure in the left eye (OS). The patient had a significant ocular history of left orbital cavernous hemangioma status post lateral orbitotomy and resection. Uncorrected visual acuity was 20/20 in the right eye (OD) and 20/40 in OS (pinhole 20/30). Funduscopic examination demonstrated optic disc edema, left eye worse than right eye, and vascular tortuosity in both eyes (OU). Late phase fluorescein angiography (FA) showed extensive perivascular and optic disc leakage and peripheral capillary leakage in OU. Laboratory evaluations were positive for human leukocyte antigen-A29 (HLA-A29). The patient was started on 40 mg prednisone daily; mycophenolate mofetil 500 mg twice daily was subsequently added.At the 3-month consultation visit to the Uveitis Clinic, dilated funduscopic examination revealed 1+ vitreous cells and improved optic disc edema in OU. FA showed improved vascular and optic disc leakage in OS but worsened leakage in OD. At this point, indocyanine green angiography (ICGA) was ordered which revealed hypocyanescent lesions throughout the choroid that were centered on the optic disc, supporting and confirming the diagnosis of BCR. Conclusions and Importance: The index patient is the first reported case of BCR in an HLA-A29 positive Asian patient.

Cataract surgery in patients with retinitis pigmentosa: systematic review.

Retinitis pigmentosa (RP) is an inherited bilateral retinal degenerative disease with an incidence of 1 in 4000 people. RP affects more than 1 million individuals worldwide. Although night blindness and restricted visual field are the most typical symptoms of these individuals, generalized vision loss due to cataracts can be expected in the latter stages of the disease. It has been demonstrated that posterior subcapsular cataract is the most prevalent cataract in younger individuals with RP, as opposed to age-related cataracts. Although most ophthalmologists may have a negative view of cataract surgery in patients with RP, it appears that it can play an important role in the visual restoration of patients with RP. However, there are concerns about performing cataract surgery for patients with RP. Herein, a systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses on databases of MEDLINE and Scopus.

Wide-Field Swept-Source Optical Coherence Tomography of Optic Disc Pit Maculopathy Demonstrates Connection Between Vitreous and Subretinal Fluid.

The source of subretinal or intraretinal fluid in patients with optic disc pit maculopathy (ODP-M) remains unclear and is often thought to be either vitreous or cerebrospinal fluid.1 Here, we present the case of a 40-year-old man who developed ODP-M. Further imaging with wide-field swept-source optical coherence tomography demonstrated that the macular fluid was tracking from a nasal optic disc pit with superonasal communication to the vitreous. This suggests that swept-source optical coherence tomography can be a useful tool for determining the origin of macular fluid in patients with ODP-M. [Ophthalmic Surg Lasers Imaging Retina 2022;53:579-581.].

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.

Serous retinal detachment as a presenting sign of acute lymphoblastic leukemia: A case report and literature review.

PURPOSE: To describe a unique case of unilateral serous retinal detachment as the presenting sign of B-cell acute lymphoblastic leukemia (ALL). OBSERVATIONS: A 74 year old woman presented with right eye blurry vision and was found to have an underlying serous retinal detachment, along with cotton wool spots, inner retinal hemorrhages, and retinal pigment epithelial changes throughout her bilateral fundi. Fluorescein angiography demonstrated bilateral vasculitis and ultrasonography revealed asymmetric thickening and enhancement of the affected eyes' choroid. This prompted a systemic lab workup and results were suspicious for an underlying hematologic malignancy. The patient was admitted to the hospital for bone marrow biopsy confirming B-cell ALL, underwent intensive intravenous and intrathecal chemotherapy, and was discharged one month later. Follow up appointment in the ophthalmology clinic demonstrated functional and anatomic improvement in the serous retinal detachment and choroidal thickening suggestive of infiltration in her right eye. CONCLUSIONS: SRDs are an uncommon ocular manifestation of leukemia, and even less common as a presenting sign of the disease. A comprehensive literature review demonstrated 11 other cases reported worldwide. We present the first such case with additional findings of leukemic retinopathy, optic nerve and choroidal infiltration, and vasculitis, as well as a complete library of ophthalmic imaging from the patient's initial presentation. IMPORTANCE: A new diagnosis of serous retinal detachment(s) without any obvious cause should raise suspicion for leukemia and prompt further workup. Early recognition of this hematologic malignancy is crucial for prompt initiation of life-saving therapy.

Racial Differences in Anti-VEGF Intravitreal Injections Among Commercially Insured Beneficiaries.

BACKGROUND AND OBJECTIVE: This study assessed racial and ethnic differences in receiving anti-vascular endothelial growth factor (VEGF) intravitreal injections among commercially insured patients. PATIENTS AND METHODS: A retrospective cohort study of 104,430 patients diagnosed with wet age-related macular degeneration (AMD), diabetic retinopathy, central retinal vein occlusion (CRVO), and branch retinal vein occlusion (BRVO) in the Optum Research Database between 2011 and 2016. Main outcomes included receiving an intravitreal anti-VEGF treatment; the first type of treatment received, if any; and subsequent treatment with ranibizumab or aflibercept among patients who were first treated with bevacizumab. RESULTS: In a logistic regression model in all 104,430 patients, Asian patients were significantly less likely to receive an anti-VEGF treatment compared to white patients (odds ratio [OR] = 0.725; 95% confidence interval [CI], 0.667-0.789; P < .001), but Black and Hispanic patients were not. Overall, 19.9% (n = 20,753) of all included patients received treatment with intravitreal injections of anti-VEGF or steroids. In multinomial logistic models of treatment type among all patients who received intravitreal injections, Hispanic patients were less likely than white patients to initially be treated with ranibizumab (relative risk ratio [RRR] = 0.776; 95% CI, 0.647-0.929; P = .006) or aflibercept (RRR = 0.794; 95% CI, 0.654-0.964; P = .020). Black and Asian patients were not significantly more or less likely to receive different types of first-line injections compared to white patients. Among 17,092 patients who received bevacizumab as first-line therapy, Hispanic patients were less likely to subsequently transition to aflibercept than their white counterparts (RRR = 0.756; 95% CI, 0.634-0.903; P = .002). CONCLUSIONS: The authors found minimal racial and ethnic differences in receiving anti-VEGF treatment among commercially insured patients with wet AMD, diabetic retinopathy, CRVO, and BRVO. These results are limited by the fact that all of the patients included were commercially insured, and there are limited data on the socioeconomic status of the patients in their sample. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:208-217.].

Differences in the characteristics of subjects achieving complete, partial, or no resolution of macular edema in the READ-3 study.

PURPOSE: To identify baseline characteristics of subjects enrolled in the READ-3 study that would predict the response of macular edema to ranibizumab (RBZ) therapy at year 1. METHODS: In this post hoc analysis of the READ-3 randomized, multicenter phase 2 clinical trial, subjects with diabetic macular edema (DME) were randomized to receive monthly intravitreal injections of RBZ (0.5 or 2.0 mg) for 6 consecutive injections followed by as-needed treatments based on pre-defined retreatment criteria. In this sub-study, subjects were divided into three groups (persistent, rebound, and resolved) based on edema status at month 12 (M12). Multi-logistic regression was utilized to assess the probability of edema outcomes M12, based on the baseline characteristics. RESULTS: One hundred twenty-three out of 152 subjects were analyzed for this sub-study. A significant difference was observed in the baseline (BL) central subfield thickness (CST) among the study groups (p < 0.05). BL CST was a significant predictor for edema outcome at M12 with > 80% probability of the subject having persistent edema if BL CST was > 570 µm (p < 0.05). This association persisted when controlled for the dose of RBZ (relative risk (RR), 1.007; p < 0.05). BL CST was also a significant predictor for having persistent edema at M12 in subjects without vitreomacular adhesion (VMA) (> 80% probability of edema persistence at CST > 570 µm [RR, 1.006; p < 0.05]). However, in the presence of VMA, BL CST was no longer a significant predictor of having persistent edema at month 12 (RR, 1.005; p > 0.05). CONCLUSIONS: Subjects with high CST (> 570 µm) at baseline may not benefit from repeated intravitreal injections of anti-VEGF for resolution of edema.