[Survey on blood thinning therapy in patients with age-related macular degeneration]. / Umfrage zur blutverdünnenden Therapie bei Patienten mit altersabhängiger Makuladegeneration.

BACKGROUND: Patients with age-related macular degeneration (AMD) often receive concomitant systemic blood thinning medications. These are known to increase the risk of severe hemorrhage also in connection with AMD, which can lead to extensive subretinal hemorrhaging. OBJECTIVE: The purpose of this study was to investigate the proportion of patients with AMD and concomitant blood thinning treatment, including the type and reason for blood thinning treatment. METHODS: This survey was prospectively conducted at the University Eye Hospital, Bonn, Germany. Volunteers were recruited during retinal consultations and the consultations for intravitreal injections (IVOM). RESULTS: The questionnaire was completed by 178 patients. The mean age was 81.7 years (58-100) and 101 patients (57.7%) were undergoing blood thinning treatment. The majority of patients were taking antiplatelet agents (n = 59; 58.4%), especially ASA (n = 55; 54.5%). Direct oral anticoagulants (DOAC) were taken by 33 patients (32.7%), including most frequently apixaban (17.8%). Vitamin K antagonists (VKA) was taken by 4 patients (4%). The most common reason for blood thinning treatment was atrial fibrillation (n = 32, 31.7%), followed by stent implantation (n = 20, 19.8%) and stroke (n = 12, 11.9%) but 13 patients (12.9%) did not know why they were undergoing blood thinning treatment. No clear indications for the use of blood thinners were found in 31 patients (30.7%). CONCLUSION: A large proportion of patients with AMD undergo blood thinning treatment; however, not every patient has a clear indication. Due to the increased risk of bleeding, the use of blood thinners should be critically evaluated in close cooperation with primary care physicians and cardiologists.

Vancomycin-Associated Hemorrhagic Occlusive Retinal Vasculitis: A Case Series and Systematic Review.

This study describes three unilateral cases of hemorrhagic occlusive retinal vasculitis (HORV) after cataract surgery and a review of the literature until February 2022, including 21 articles reporting HORV cases. Altogether, 61 eyes (41 patients) were included. Twenty patients had bilateral and 21 patients had unilateral HORV. Prophylactic vancomycin was given to all patients. Additional vancomycin use was associated with the worst outcome. The mean time to HORV was 9 days post-cataract surgery. In bilateral cases, the median time between surgeries was 7 days. Visual acuity was < 20/400 in 48%, with no light perception in 20%. Neovascular glaucoma developed in 43%. Central macular thickening or hyperreflectivity of the inner retinal layers on optical coherence tomography was associated with worse outcomes. Corticosteroid treatment, early panretinal laser photocoagulation, or anti-vascular endothelial growth factor therapy, and prophylaxis alternative to vancomycin is recommended. [Ophthalmic Surg Lasers Imaging Retina 2022;53:702-712.].

Development of subretinal hemorrhage after treatment discontinuation for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: To investigate the incidence, risk factors, and their influence on visual outcomes of subretinal hemorrhage (SRH) in patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy(PCV) who discontinue treatment. METHODS: This retrospective study included 148 patients with nAMD and PCV who discontinued treatment. The development of a 3-disc area or greater extent of SRH after treatment discontinuation was identified. Visual acuity at the final visit was compared between patients with and those without SRH. Factors associated with SRH were then analyzed. RESULTS: During the mean 56.8 ± 18.2 months of follow-up, treatment was discontinued at a mean 24.1 ± 16.3 months after diagnosis. SRH developed in 24 (16.2%) patients at a mean 21.5 ± 17.6 months after treatment discontinuation. The visual acuity at the final follow-up was significantly worse in patients with SRH than in those without SRH (P < 0.001). There was a significant difference in the incidence of SRH among the different types of macular neovascularization (MNV) (P = 0.024). In particular, the incidence of type 3 MNV was relatively high (36.0%). CONCLUSIONS: The development of SRH may lead to very poor visual prognosis in patients who discontinue treatment. The high risk of SRH in type 3 MNV suggests the need for caution when choosing treatment discontinuation in cases of type 3 MNV.

Acute Onset Optic Disc Hemorrhage Following Pharmacologic Mydriasis.

PURPOSE: The aim was to report 2 unusual cases of optic disc hemorrhage (DH) occurring following pharmacologic mydriasis. OBSERVATION: A 78-year-old woman and 60-year-old man with primary open angle glaucoma developed optic DHs shortly after pupillary dilation. CONCLUSION AND IMPORTANCE: Cycloplegia may cause subtle shifts in vitreous and lamina cribrosa position that may result in the formation of optic DHs in susceptible glaucomatous eyes.

BACILLARY LAYER DETACHMENT BECAUSE OF MACULAR NEOVASCULARIZATION.

PURPOSE: To describe the clinical and multimodal imaging features of bacillary layer detachment (BD), and its response to intravitreal anti-vascular endothelial growth factor therapy, in eyes with macular neovascularization. METHODS: Retrospective, observational case series of 14 eyes (14 patients, 7 men) imaged with eyes (14 patients, 7 men) were imaged with spectral-domain optical coherence tomography, and either fluorescein angiography or optical coherence tomography angiography. Therapeutic response was monitored with serial imaging and best-corrected visual acuity assessments. RESULTS: The mean age was 75 ± 13 (range: 45-96) years, with mean follow-up duration of 27 ± 21 (range: 1-56) months. Neovascular age-related macular degeneration was found in 71% (10/14) eyes. Type 2 macular neovascularization lesions were associated with BD in all 14 eyes. Subretinal hemorrhage was noted in 79% (11/14) eyes. BD promptly resolved after intravitreal antivascular endothelial growth factor therapy in all eyes. The baseline best-corrected visual acuity improved from logarithm of the minimum angle of resolution 0.84 ± 0.32 (Snellen equivalent 20/138) to logarithm of the minimum angle of resolution 0.48 ± 0.31 (Snellen equivalent 20/60) at the last follow-up, with treatment of the macular neovascularization. CONCLUSION: Type 2 macular neovascularization and subretinal hemorrhage are associated with BDs, which may be due to a rapid influx of exudative fluid into the potential space between the external limiting membrane and ellipsoid zone. Intravitreal antivascular endothelial growth factor therapy results in rapid resolution of BDs and visual improvement in most eyes.

HEMORRHAGIC OCCLUSIVE RETINAL VASCULITIS AFTER INTRACAMERAL VANCOMYCIN USE IN CATARACT SURGERY AFTER INTRAVENOUS EXPOSURE.

PURPOSE: To report a case of hemorrhagic occlusive retinal vasculitis after cataract surgery. METHODS: A 74-year-old woman presented with blurry vision and distorted vision, which started 2 days after an uncomplicated cataract surgery in the left eye. Intracameral vancomycin was injected during the case. The patient reported being treated with systemic vancomycin in the past. RESULTS: The visual acuity was 20/80 in the left eye. She had trace cells in the anterior chamber with no hypopyon and intraocular lens implant within the capsular bag in the left eye. Dilated fundus examination revealed no vitritis, There were large patches of peripheral retinal hemorrhages and retinal ischemia. The patient was diagnosed with hemorrhagic occlusive retinal vasculitis likely secondary to hypersensitivity reaction to intracameral vancomycin. The patient was started on oral prednisone, and the topical difluprednate course was escalated. Within 3 weeks, vision improved to 20/30 in the left eye. She underwent pan retinal photocoagulation targeting the ischemic areas in the periphery. CONCLUSION: The patient had previous exposure to systemic vancomycin, which may have sensitized her immune system. Later on, the hypersensitivity reaction took place after exposure to intracameral vancomycin during cataract surgery. Our hemorrhagic occlusive retinal vasculitis case had a favorable visual outcome, and recognition of this entity will ensure that vancomycin will not be used for infection prophylaxis in the fellow eye at the time of cataract surgery.

Ocular Complications of Checkpoint Inhibitors and Immunotherapeutic Agents: A Case Series.

Background: Ophthalmologists have a role in assessing immune-related adverse events (IRAE) in oncology patients on immunotherapy. We assessed the utility of a hospital-wide toxicity team in referring patients with new ocular symptoms for examination. We also identified new immunotherapy agents causing ocular side-effects.Design: A cohort study of eight consecutive patients on immunotherapy, who developed ocular IRAE from November 1, 2017 to June 30, 2019. All were seen at the Ocular Immunology Division of the Wilmer Eye Institute and referred by the Johns Hopkins Toxicity Team.Results: All eight patients on had IRAEs; were treated with corticosteroid drops or observation with clinical resolution. Two new agents, epocadostat and daratumumab, were associated with the development of uveitis.Conclusion: Ophthalmologists play an important role in a hospital-wide toxicity team and need to include IRAEs in their differential diagnosis. Given new drug development, ophthalmologists may be the first to identify IRAEs.

Successful Clinical Outcome of Vancomycin-induced Hemorrhagic Occlusive Retinal Vasculitis.

We present a case of a patient that experienced severe hemorrhagic occlusive retinal vasculitis secondary to injection of 1.0 mg/0.1 ml of intracameral vancomycin for endophthalmitis prophylaxis after an uneventful cataract surgery. The case is especially unique in that our patient ended up maintaining 20/25 vision with an ocular disease that is typically visually threatening. This may be due to the aggressive administration of periocular and oral steroids combined with scheduled anti-VEGF injections that were later transitioned into a treat and extend regimen.

REVERSIBLE RETINAL TOXICITY IN A PATIENT TAKING AXITINIB.

PURPOSE: Axitinib (Inlyta, New York, NY) is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma after failure of one previous systemic therapy. A case of bilateral retinal hemorrhages and cotton wool spots associated with axitinib is reported. METHODS: A 62-year-old woman with a 4-year history of renal cell carcinoma with metastases was treated with axitinib at a maximum oral daily dose of 8 mg. Soon after beginning higher dose therapy, she developed blurred vision, floaters, and photopsias. RESULTS: Funduscopic examination of both eyes revealed cotton wool spots and retinal hemorrhages that improved with cessation of therapy. CONCLUSION: Axitinib may be associated with microangiopathic retinal toxicity.

The Timing of Large Submacular Hemorrhage Secondary to Age-Related Macular Degeneration Relative to Anti-VEGF Therapy.

PURPOSE: To characterize the timing of large submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (AMD) relative to anti-vascular endothelial growth factor (VEGF) therapy. DESIGN: Retrospective, consecutive case series. PARTICIPANTS: The study included 46 eyes of 46 patients with large SMH resulting from neovascular AMD selected to undergo pars plana vitrectomy with subretinal tissue plasminogen activator at the Mid Atlantic Retina group of the Wills Eye Hospital. METHODS: Patient charts were reviewed to identify baseline characteristics and anti-VEGF treatment details. OCT was used to evaluate pigmented epithelial detachments, SMH, and subretinal fluid before and after SMH. MAIN OUTCOME MEASURES: The timing of SMH in relation to last anti-VEGF injection, the anti-VEGF treatment status (i.e., naive, stable, or recently extended or shortened) at the time of SMH, and the length of the anti-VEGF treatment interval at the time of bleeding. RESULTS: Submacular hemorrhage occurred in 15 patients (36%) who were treatment naive. In patients treated with anti-VEGF, 19 (45%) had a stable treatment interval, 5 (12%) had a recently extended interval, and 3 (7%) had a shortened interval. The average treatment interval at the time of SMH was 6.8 weeks with a median of 7 total injections before SMH. Seven treated patients (26%) experience an SMH while having a 4-week dosing interval. The average time between last injection and SMH was 29 days. Forty-eight percent of patients treated with anti-VEGF agents experienced an SMH within 30 days of anti-VEGF injection. Chi-square analysis found SMH more likely to occur within 30 days of anti-VEGF injection than after 30 days. CONCLUSIONS: Large SMH in neovascular AMD in a treat-and-extend regimen does not seem to be associated with prolonged dosing intervals or recent interval extension, and a large proportion of such hemorrhages are likely to be a result of mechanisms other than loss of effective VEGF inhibition.

Case Report: Transient Myopic Shift and Other Sequelae in Response to Adverse Reaction to Sulfamethoxazole-trimethoprim.

SIGNIFICANCE: There are several isolated reports of systemic medications or medical conditions that can cause acute transient myopic shifts along with other ocular sequelae, but rarely has this been reported for the combination antibiotic sulfamethoxazole-trimethoprim. PURPOSE: This case illustrates a rarely seen condition that may result from treatment with sulfamethoxazole-trimethoprim and result in serious, vision-threatening conditions. These can be treated by immediate discontinuation of the drug, steroids, ocular hypertensive medication, and cycloplegia, depending on the circumstances. CASE REPORT: A 20-year-old woman presented complaining of blindness upon waking. She had been experiencing fever, malaise, and significant abdominal pain for weeks. Blood culture revealed infection with Staphylococcus aureus and Escherichia coli for which she was prescribed sulfamethoxazole (800 mg) and trimethoprim (160 mg) twice daily. After a week of treatment, she awoke unable to see. Examination revealed narrowed angles, bilateral 6-D myopic shift, macular folding with scattered microaneurysms, and intraretinal hemorrhages with mild macular edema and field defects. The condition resolved with discontinuation of the drug and use of steroids, ocular hypertensive, and cycloplegic agents. Her visual acuity returned to near normal within 3 days. Resolution of macular edema, field defects, and hemorrhages followed. CONCLUSIONS: An adverse reaction possibly caused by sulfamethoxazole-trimethoprim is described causing ciliochoroidal effusion resulting in acute myopic shift and other sequelae. Successful treatment is demonstrated, and implications are discussed.

Ocular Adverse Effects of Amiodarone: A Systematic Review of Case Reports.

SIGNIFICANCE: Amiodarone is an excellent antiarrhythmic medication; however, it has numerous systemic and ocular adverse effects. PURPOSE: We aimed to improve our understanding of amiodarone and its ocular adverse effects by performing a systematic review and meta-analysis of published case reports. METHODS: This systematic review was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We used the MEDLINE database, primarily through PubMed, and used keywords (amiodarone, eye, eye diseases, visual/ocular adverse effects/manifestations) to identify case reports of ocular adverse effects after amiodarone use. The initial search resulted in 92 total case reports. However, after excluding nonrelevant case reports, 25 cases were selected for the final analysis. RESULTS: Among the patients in the 25 case reports, 18 were male (72%), and the median age was 66 ± 9.9 years. In 15 cases (60%), the patients reported halos around light and/or decrease in vision after amiodarone use. The most common ophthalmic examination findings were cornea verticillata/vortex keratopathy in 19 cases (76%), followed by different patterns of papilledema and retinal hemorrhages in 5 cases (20%). Discontinuation of amiodarone was the most common intervention, followed by application of topical heparin. Outcomes among case reports were variable. CONCLUSIONS: Cornea verticillata/vortex keratopathy was the most common ocular adverse effect in cases where amiodarone was administered. Early recognition of amiodarone-induced ocular adverse effects is imperative to prevent worsening keratopathy or uncommon adverse effects. Collaboration between physicians prescribing amiodarone-to recognize the ocular symptoms-and referral to eye care physicians are important.

Phase 3, Randomized, Double-Blind, Active-Comparator (Darbepoetin Alfa) Study of Oral Roxadustat in CKD Patients with Anemia on Hemodialysis in Japan.

BACKGROUND: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved in China for dialysis-dependent CKD anemia. METHODS: This phase 3, 24-week, double-blind, double-dummy study evaluated roxadustat's noninferiority to darbepoetin alfa for hemodialysis-dependent CKD anemia. We randomly assigned Japanese patients to oral roxadustat three times weekly or to darbepoetin alfa injections once weekly, titrating doses to maintain hemoglobin between 10-12 g/dl. The primary end point was change of average hemoglobin from baseline to weeks 18-24 (∆Hb18-24). Secondary end points were average hemoglobin and proportion of patients with hemoglobin between 10-12 g/dl (maintenance rate) at weeks 18-24, and iron parameters. Safety assessments included treatment-emergent adverse events and adjudicated ophthalmologic findings. RESULTS: We randomly assigned 303 patients to roxadustat (n=151) or darbepoetin alfa (n=152). The difference between roxadustat and darbepoetin alfa in ∆Hb18-24 was -0.02 g/dl (95% confidence interval, -0.18 to 0.15), confirming roxadustat's noninferiority to darbepoetin alfa. Average hemoglobin at weeks 18-24 with roxadustat was 10.99 g/dl (95% confidence interval: 10.88 to 11.10), confirming its efficacy. Among patients with one or more hemoglobin value during weeks 18-24, the maintenance rate was 95.2% with roxadustat and 91.3% with darbepoetin alfa. Serum iron, ferritin, and transferrin saturation remained clinically stable with roxadustat; transferrin and total iron binding capacity increased through week 4 before stabilizing. Common treatment-emergent adverse events were nasopharyngitis, shunt stenosis, diarrhea, contusion, and vomiting. The proportion of patients with new or worsening retinal hemorrhage was 32.4% with roxadustat and 36.6% with darbepoetin alfa. We observed no clinically meaningful changes in retinal thickness groups. CONCLUSIONS: Roxadustat maintained hemoglobin within 10-12 g/dl in patients on hemodialysis and was noninferior to darbepoetin alfa. Treatment-emergent adverse events were consistent with previous reports. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: A Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis Chronic Kidney Disease Patients with Anemia, NCT02952092 (ClinicalTrials.gov).

Perioperative risk of bleeding with antithrombotic agents in macular surgery: a national, prospective, multicentre study.

PURPOSE: To compare the risk of haemorrhagic complications in elective macular surgery between patients with no antithrombotic (AT) treatment (defined as patients with no history of AT therapy or who discontinued AT therapy) and patients who continued AT treatment during the surgery. METHODS: E-case report forms were prospectively recorded in a database before vitreoretinal surgery and 1 month after. Data on patient characteristics, surgical techniques, haemorrhagic complications and antithrombotic status were collected. Patients with retinal detachment, proliferative diabetic retinopathy and previous retinal haemorrhage were excluded. RESULTS: A total of 748 procedures (single procedure in one eye per patient) were performed between January and May 2019. Among them, 202 patients (27.0%) were treated with antithrombotic therapy at the time of surgery: 19.5% with antiplatelet agents (n = 146), 6.3% with anticoagulants (n = 47) including 3.2% (n = 24) patients treated with novel oral anticoagulants, 0.8% (n = 6) with anticoagulants and antiplatelet agents, and 0.4% (n = 3) with heparin. Overall, 92 patients (12.3%) developed one or more haemorrhagic complications, of which 63 (11.5%) and 29 (14.4%) were in the non-AT and AT group, respectively. The multivariate logistic regression model showed no difference between AT treatment groups regarding ocular bleeding complications (odds ratio [OR] 1.2, 95% confidence interval (CI) [0.7-2.2], p = 0.54). CONCLUSION: No cases of uncontrolled or severe perioperative haemorrhage in patients continuing antithrombotic agents were reported in this selected population. For the majority of the patients taking antiplatelets or anticoagulants, these agents could be safely continued during macular surgery.

Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia.

STAT3 gain-of-function (GOF) mutations can be responsible for an incomplete phenotype mainly characterized by hematological autoimmunity, even in the absence of other organ autoimmunity, growth impairment, or severe infections. We hereby report a case with an incomplete form of STAT3 GOF intensified by a concomitant hereditary hematological disease, which misleads the diagnosis. The patient presented with lymphadenopathy, splenomegaly, hypogammaglobulinemia, and severe autoimmune hemolytic anemia (AIHA) with critical complications, including stroke. A Primary Immune Regulatory Disorders (PIRD) was suspected, and molecular analysis revealed a de novo STAT3 gain-of-function mutation. The response to multiple immune suppressive treatments was ineffective, and further investigations revealed a spectrin deficiency. Ultimately, hematopoietic stem cell transplantation from a matched unrelated donor was able to cure the patient. Our case shows an atypical presentation of STAT3 GOF associated with hereditary spherocytosis, and how achievement of a good long-term outcome depends on a strict clinical and laboratory monitoring, as well as on prompt therapeutic intervention.

ASSOCIATION BETWEEN ORAL IRON SUPPLEMENTATION AND RETINAL OR SUBRETINAL HEMORRHAGE IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENT TRIALS.

PURPOSE: Because patients often take iron supplements without medical indication, and iron can accumulate in vascular endothelial cells, the authors evaluated the association of oral iron supplementation with retinal/subretinal hemorrhage in patients with neovascular age-related macular degeneration. METHODS: A post hoc secondary data analysis of comparison of age-related macular degeneration treatments trials was performed. Participants were interviewed for use of oral iron supplements. Trained readers evaluated retinal/subretinal hemorrhage in baseline fundus photographs. Adjusted odds ratios from multivariate logistic regression models assessed the association between iron use and baseline hemorrhage adjusted by age, sex, smoking, hypertension, anemia, and use of antiplatelet/anticoagulant drugs. RESULTS: Among 1,165 participants, baseline retinal/subretinal hemorrhage was present in the study eye in 71% of 181 iron users and in 61% of 984 participants without iron use (adjusted odds ratio = 1.47, P = 0.04), and the association was dose dependent (adjusted linear trend P = 0.048). Iron use was associated with hemorrhage in participants with hypertension (adjusted odds ratio = 1.87, P = 0.006) but not without hypertension. The association of iron use with hemorrhage remained significant among hypertensive participants without anemia (adjusted odds ratio = 1.85, P = 0.02). CONCLUSION: Among participants of comparison of age-related macular degeneration treatments trials, the use of oral iron supplements was associated with retinal/subretinal hemorrhage in a dose-response manner. Unindicated iron supplementation may be detrimental in patients with wet age-related macular degeneration.