Acute Kidney Injury from Intravitreal Anti-vascular Endothelial Growth Factor Drugs: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Several observational studies have reported acute kidney injury from intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs for retinal diseases. However, systematic reviews and meta-analyses of randomized controlled trials on this critical topic are scant. OBJECTIVE: To evaluate acute kidney injury risk associated with intravitreal anti-VEGF drugs in patients with retinal diseases. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials on 12 July, 2023, and included randomized controlled trials reporting acute kidney injury between anti-VEGF drugs (e.g., aflibercept, bevacizumab, brolucizumab, and ranibizumab) and controls for retinal diseases (e.g., age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic retinopathy/diabetic macular edema, retinal vein occlusion, and myopic choroidal neovascularization). Data were synthesized by a fixed-effects model for pooling odds ratios (ORs) using the Peto method. RESULTS: We included 13 randomized controlled trials (four and nine trials for aflibercept and ranibizumab, respectively) with a total of 4282 participants. The meta-analysis indicated intravitreal anti-VEGF drugs did not increase the acute kidney injury risk, compared with controls (odds ratio [OR]: 1.00, 95% confidence interval [CI] 0.49-2.04, I2: 0%), and no differences in the acute kidney injury risk were observed between different anti-VEGF drugs (OR: 1.10, 95% CI 0.27-4.43, I2: 0% for aflibercept; OR: 0.97, 95% CI 0.42-2.22, I2: 0% for ranibizumab) and between different retinal diseases (OR: 4.61, 95% CI 0.07-284.13, I2: not applicable for age-related macular degeneration; OR: 0.90, 95% CI 0.42-1.93, I2: 0% for diabetic retinopathy/diabetic macular edema; OR: 1.57, 95% CI 0.16-15.88, I2: 0% for retinal vein occlusion). CONCLUSIONS: Intravitreal anti-VEGF drugs were not associated with an acute kidney injury risk, regardless of which anti-VEGF drugs (aflibercept or ranibizumab) or retinal diseases (age-related macular degeneration, diabetic retinopathy/diabetic macular edema, or retinal vein occlusion) were involved. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO CRD42021267854.

Risk of retinal vein occlusion in colorectal cancer patients receiving anti-vascular endothelial growth factors - a population-based cohort study.

BACKGROUND: Anti-vascular endothelial growth factors (VEGFs) treatment has been associated with an increased risk of thromboembolic events. Therefore, the use of anti-VEGFs for patients with colorectal cancers (CRC) has raised concerns about the potential risk of retinal vein occlusion (RVO), an ocular disease caused by embolism or venous stasis. This study aims to evaluate the risk of RVO in patients with CRC treated with anti-VEGFs. METHOD: We conducted a retrospective cohort study using the Taiwan Cancer Registry and National Health Insurance Database. The study cohort comprised patients newly diagnosed with CRC between 2011 and 2017, who received anti-VEGF treatment. For each patient in the study cohort, a control group comprising four patients newly diagnosed with CRC, but not receiving anti-VEGF treatment, was randomly selected. A washout period of 12 months was implemented to identify new cases. The index date was defined as the date of the first prescription of anti-VEGF drugs. The study outcome was the incidence of RVO, as identified by ICD-9-CM (362.35 and 362.36) or ICD-10-CM codes (H3481 and H3483). Patients were followed from their index date until the occurrence of RVO, death or the end of the study period. Covariates, including patients' age at index date, sex, calendar year of CRC diagnosis, stage of CRC and comorbidities related to RVO, were included. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HRs) with adjustments for all covariates to compare the risk of RVO between the anti-VEGF and control groups. RESULTS: We recruited 6285 patients in the anti-VEGF group and 37,250 patients in the control group, with mean ages of 59.49 ± 12.11 and 63.88 ± 13.17 years, respectively. The incidence rates were 1.06 per 1000 person-years for the anti-VEGF group, and 0.63 per 1000 person-years for the controls. There was no statistically significant difference in RVO risk between the anti-VEGF and control groups (HR: 2.21, 95% CI: 0.87-5.61). CONCLUSION: Our results indicated no association between use of anti-VEGF and occurrence of RVO among CRC patients, although the crude incidence rate of RVO was higher in patients receiving anti-VEGF, compared to control patients. Future study with larger sample size is required to confirm our findings.

Bilateral Optic Neuritis after COVID-19 Vaccination: A Case Report.

BACKGROUND: Neuro-ophthalmic manifestations after vaccines are rare, with optic neuritis (ON) being the most common presentation. Patients with vaccine-related ON are similar to those with idiopathic ON. The temporal relationship between vaccination against and the occurrence of ON is vital. Here, we report a case of bilateral ON after the administration of the ChAdOx1-S nCoV-19 SARS-CoV-2 vaccine. CASE: A 49-year-old healthy Asian female presented with sudden onset of bilateral blurred vision within 2 days. She complained of photophobia and extraocular pain upon movement over 3 days. Upon examination, her best corrected visual acuity (BCVA) was 20/30 in the right eye and 20/200 in the left eye. Anterior segment findings were unremarkable, with normal intraocular pressure. Fundoscopic examination revealed bilateral disc edema with vessel engorgement. Visual field examination revealed profound visual field defect in both eyes. She denied any trauma, use of new medication or medical history. She had received the ChAdOx1 nCoV-19 SARS-CoV-2 vaccine 14 days prior. Under suspicion of vaccine-related optic neuritis, she was given intravenous methylprednisolone 1 gm/day for 3 days, shifting to oral prednisolone under gradual tapering for 2 weeks. CONCLUSIONS: Typically presenting with sudden-onset visual decline and extraocular pain during movement, acute ON is generally idiopathic. Bilateral ON is rare, but quick identification is important because it can potentially lead to permanent loss of vision if left untreated. Vaccination-induced ON is even rarer but not difficult to treat. However, such patients require further evaluation and long-term follow-up because they may be prone to other neurological disorders in the future.

Serous retinal detachment secondary to an unsuccessful transarterial embolization in a post-traumatic carotid-cavernous sinus fistula patient: A case report.

A carotid-cavernous sinus fistula (CCF) is an abnormal communication between the cavernous sinus and the carotid arterial system. Direct CCFs arise from a direct connection between the cavernous sinus and the cavernous portion of the internal carotid artery. Nowadays, endovascular neurosurgery has become the first-line treatment modality for direct CCFs owing to the high complete obliteration rate. However, reversal of the clinical symptoms may not always be congruous after the endovascular intervention. Herein, we present a 50-year-old patient who manifested diplopia, ophthalmoplegia, and orbital congestion after a traffic accident. He had suffered head injury with right side frontal intracranial hemorrhage 1 month before the ophthalmic presentation. He came to our department primarily because of declining vision and for the above symptoms, and was diagnosed with direct type CCF, for which he received transarterial coil embolization. Unexpectedly, he later presented with serous retinal detachment accompanied by ocular ischemic syndrome secondary to recurrent CCF 1 month after the intervention, so repeat coil embolization was performed.

The Role of Corticosteroids in Treating Acute Ocular Toxoplasmosis in an Immunocompetent Patient: A Case Report.

Background: This study aimed to report a case who was treated with corticosteroids and anti- parasitic agents for ocular toxoplasmosis, but who progressed to acute retinal necrosis, and finally retinal detachment. Case Presentation: A 42-year-old man presented to the ophthalmology clinic with a 1-month history of progressive blurred vision and floaters in his right eye. His best visual acuity (VA) was 20/20 in both eyes. The anterior segment was unremarkable. Funduscopic examination of the right eye revealed active lesions of whitish foci of chorioretinitis with surrounding edema along the superonasal vessels, and retinal vasculitis with perivascular sheathing. Serologic testing was positive for Toxoplasma gondii IgM and IgG, but negative for other virus- and syphilis infections. Ocular toxoplasmosis was diagnosed. Corticosteroids and anti-parasitic agents were given simultaneously, but his right eye VA became 20/100. Funduscopic examination revealed retinal necrosis with localized retinal breaks. We immediately performed focal photocoagulation, however, his right eye progressed to retinal detachment and required vitrectomy. Conclusion: Early administration of systemic corticosteroids in patients with acquired acute ocular toxoplasmosis may lead to complications that impair vision. Intensive observation should be arranged after corticosteroid use.

Orbital Apex Syndrome: A Case Series in a Tertiary Medical Center in Southern Taiwan.

Background: Orbital apex syndrome (OAS) is a rare ocular complication following by infection, inflammation, trauma, neoplasms, and vascularity. The epidemiological features of OAS remained limited, so this study aimed to present ophthalmic clinical features, determine the causes to evaluate the visual prognosis of orbital apex syndrome (OAS) patients in Taiwan. Methods: This was a retrospective study by reviewing the electronic medical records from National Cheng Kung University Hospital in Taiwan during 2017-2019. We included patients diagnosed with OAS to review their ocular symptoms and signs, visual acuity, ocular images, etiologies, treatment and visual prognosis. Results: Twenty cases (mean age: 65.55 ± 13.06; male: 75%) with the diagnosis of OAS were included in this study. All patients presented as unilateral involvement, but the initial ocular presentations and etiologies varied. For example, blurred vision was reported in 80% of these patients, and tumor-related compression (55%) and infection (15%) were the most frequent causes for the OAS. After the follow-up, we found 35% of patients' visions declined or worsened to the blindness, 15% of patients' visions remained stable, 20% of patients' visions had mild improvement, and 35% of patients' visions were not measured because of debilitating clinical condition. We identified three OAS patients with mortality (15%), and all of them were attributed to the underlying malignancies. Conclusion: The clinical magnifications and etiologies of OAS are heterogeneous in Taiwan. Our findings indicated the tumor-related compression is the most frequent causes of OAS in Taiwan, and it is also related to poor clinical outcomes.

Effect Modification by Indication to the Risks of Major Thromboembolic Adverse Events in Patients Receiving Intravitreal Anti-Vascular Endothelial Growth Factor Treatment: A Population-Based Retrospective Cohort Study.

BACKGROUND: The association between intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment and the risk of major thromboembolic adverse events (TAEs) remains under debate. This study aimed to examine associated risks of TAEs in patients receiving intravitreal anti-VEGF treatment, and effect modification by different indications. METHODS: This retrospective cohort study analyzed Taiwan's National Health Insurance Database during 2011-2017 to identify neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) patients newly receiving intravitreal aflibercept or ranibizumab. We followed up patients for 2 years, or until the occurrence of TAEs, including ischemic heart disease, ischemic stroke, transient ischemic attack, deep vein thrombosis, and pulmonary embolism, death, or the end of the study period (i.e., 31 December 2018). We compared the risk of TAEs between patients with aflibercept and ranibizumab using Cox-proportional hazard models. We examined statistical interactions between the anti-VEGF treatment (i.e., ranibizumab and aflibercept) and indications (i.e., nAMD and DME) with regard to the outcome of TAEs. RESULTS: We included 12,215 nAMD and 7532 DME patients. Among nAMD patients, those receiving aflibercept had lower risk of TAEs (adjusted hazard ratio [HR] 0.85; 95% CI 0.77-0.94) compared with those receiving ranibizumab. However, among DME patients, those receiving aflibercept had no differences in the risk of TAEs (1.14; 0.97-1.35) compared with those receiving ranibizumab. Among patients treated with ranibizumab, the DME group had a higher risk of TAEs than the nAMD group (HR 1.15; 95% CI 1.03-1.28); similar results were observed in patients treated with aflibercept (HR 1.53; 95% CI 1.27-1.85). When DME patients were treated with aflibercept, the risk of TAEs was 31% higher than when nAMD patients were treated with ranibizumab (HR 1.31; 95% CI 1.09-1.56; p < 0.05). The p-value for statistical interaction between the anti-VEGF treatment and indications was 0.0033. CONCLUSIONS: Patients treated with aflibercept or ranibizumab for different indications may be associated with varying risk of TAEs. The findings provide evidence to support treatment selection, taking indications and TAE risk into consideration.

Rare presentations of primary amyloidosis as ptosis: a case report.

BACKGROUND: Amyloidosis is a rare, progressive and variable group of diseases characterized by extracellular deposits of amyloid protein in different tissues and organs. It is a protein-misfolding disease in which small proteins of about 10 to 15 kDa acquire an alternative and relatively misfolded state at minimum energy and subsequently aggregate into oligomers and polymers. It mimics other eyelid diseases, such as involutional ptosis, eyelid granulomatous or cancerous lesions. Misdiagnosis of eyelid amyloidosis is usual when the lesion grows slowly and insidiously. Definite diagnosis depends on clinical suspicion and tissue-proven biopsy. CASE PRESENTATION: A 50-year-old female had painless progressive ptosis in both eyes for 6 months. She presented with limited upward gaze due to swelling of the upper eyelids OU. She complained of mild foreign body sensation. Upon examination, we observed an infiltrated irregular yellowish mass on the surface of her upper palpebral conjunctiva in both eyes. The mass was non-movable without tenderness. We performed excisional biopsy for the masses and subsequent histopathology of the biopsy specimens revealed amyloidosis. Systemic workup showed no other lesions. Unfortunately, her ptosis and upward gaze restriction was not improved after the operation. However, the masses did not enlarge in the following 3 months. CONCLUSIONS: The varied presentations of ocular adnexal and orbital amyloidosis often lead to a significant delay between first symptoms and diagnosis. Immediate confirmatory biopsy and subsequent systemic workup should be performed whenever amyloidosis is highly suspected.

Adult inclusion conjunctivitis diagnosed by polymerase chain reaction and Giemsa stain.

Adult inclusion conjunctivitis, caused by Chlamydia trachomatis, is easily underdiagnosed with nonspecific ocular manifestation. Combined scrape cytology and molecular testing may be a useful strategy for its early diagnosis. A 24-year-old healthy male complained of blurred vision, foreign body sensation, and watery discharge in his right eye for four weeks. His visual acuity was 20/20 bilaterally at his first visit. Allergic conjunctivitis was the first impression, and topical treatment with corticosteroid and anti-histamine was prescribed. However, he returned five days later without symptom improvement, and his right eye vision declined to 20/40. Subepithelial corneal infiltration of his right eye was observed. According to his personal history, his girlfriend was diagnosed with sexually transmitted chlamydial infection and genital gonorrhea. Under the suspicion of sexually transmitted adult inclusion conjunctivitis, we collected his conjunctival lavage to both real-time polymerase chain reaction, which proved chlamydial infection, and Giemsa stain, which demonstrated typical basophilic intracytoplasmic inclusions. To diagnose adult inclusion conjunctivitis, we can use real-time polymerase chain reaction or Giemsa stain to help us obtain a quick and correct diagnosis.

Tolosa-Hunt syndrome as initial presentation of Systemic Lupus Erythematosus.

PURPOSE: Case presentation of newly diagnosed systemic lupus erythematosus (SLE) presenting initially as Tolosa-Hunt syndrome (THS). STUDY DESIGN: Retrospective clinical case. METHOD: Case report. RESULTS: A healthy young man developed acute binocular diplopia within 2 days without other neurological deficits. Bilateral 6th cranial nerve palsy was observed with general reduction in the visual field test. Emergent brain magnetic resonance image (MRI) was performed, which revealed severe inflammation in the cavernous sinus, superior orbital fissure, and apex of the orbit. No cavernous thrombosis or intracranial lesion was shown in the MRI. THS was diagnosed and the patient's CN 6 palsy recovered quickly after corticosteroid treatment. However, severe anaemia was discovered during admission (Hb=6.0), so the patient was evaluated by profound laboratory tests, which revealed SLE. CONCLUSION: With painful ophthalmoplegia, cavernous sinus syndrome is highly suspected. THS is one of the differential diagnoses for cavernous sinus syndrome. THS is a rare disease, recognized by the National Organization for Rare Disorders, and characterized by inflammatory changes in the cavernous sinus, superior orbital fissure and/or orbital apex under image study. The inflammatory changes are mostly idiopathic, but secondary causes such as sarcoidosis or other autoimmune diseases need to be ruled out. Physicians should be aware of possible underlying conditions, such as immunosuppressed status as in SLE, as the true cause of THS.

Comparative Risk of Arterial Thromboembolic Events Between Aflibercept and Ranibizumab in Patients with Maculopathy: A Population-Based Retrospective Cohort Study.

BACKGROUND: The increasing numbers of elderly patients and rising incidence of maculopathy raise concerns over arterial thromboembolic events (ATEs) with the use of intravitreal anti-vascular endothelial growth factor (VEGF) medications. OBJECTIVES: This study aimed to compare the risk of ATEs between aflibercept and ranibizumab for maculopathy. METHODS: We conducted a retrospective population-based cohort study analyzing Taiwan's National Health Insurance Database during 2011-2017 to identify patients with maculopathy receiving intravitreal aflibercept or ranibizumab. The primary outcome was any hospitalization or emergency room visit because of ATEs, including ischemic heart disease (IHD), ischemic stroke (IS), and transient ischemic attack (TIA). The secondary outcome was mortality within 30 days after occurrence of ATE. We employed propensity score methods to generate more homogeneous groups for comparison. RESULTS: We included 5791 aflibercept users and 14,534 ranibizumab users in this study. Compared with the ranibizumab group, the aflibercept group was associated with a lower risk of ATE (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.80-0.91), with HRs of 0.86 for IHD (95% CI 0.80-0.93), 0.87 for IS (95% CI 0.76-1.00), and 0.57 for TIA (95% CI 0.46-0.71). The risk of 30-day mortality after ATE (HR 1.39; 95% CI 0.80-2.43) and the risk of all-cause mortality (HR 1.02; 95% CI 0.89-1.17) in the aflibercept group was similar to that in the ranibizumab group. CONCLUSION: The use of aflibercept in patients with maculopathy was associated with a lower risk of ATE than was the use of ranibizumab. There was no difference in mortality risk between the two groups. Our study could provide strong grounds for future prospective studies to confirm the findings.

Risk of age-related macular degeneration in aspirin users and non-aspirin users: A population-based cohort study in Taiwan.

BACKGROUND: The association between cardioprotective aspirin and risk of age-related macular degeneration (AMD) is still controversial up to date. We aimed to analyze the risk of AMD between aspirin users and non-aspirin users. METHOD: This was a retrospective cohort study by using claims data from the National Health Insurance Research Database. Patients aged more than 45 years old who initiated aspirin during 2002 to 2012 were followed till 2013. We first selected an age and sex-matched cohort, then identified aspirin users and non-aspirin users as propensity score-matched cohort. Cox proportional hazard regression model was applied to compare their hazards and 95% confidence intervals. Incidence of newly developed AMD, neovascular AMD, and other-AMD was calculated. RESULTS: We identified 204 085 regular aspirin users and 478 048 non-aspirin users from our datasets. The univariate HR was 2.85 (95% CI, 2.75-2.96), and the multivariate HR was 2.54 (95% CI, 2.44-2.65). In the PS-matched cohort, the HR was 2.38 (95% CI, 2.25-2.52). The incidence of aspirin users for AMD risk was 11.95 per 1000 person-year, while the incidence of non-aspirin users was only 3.92 per 1000 person-year. CONCLUSION: Patients with regular use of aspirin had higher risk in developing AMD compared to non-aspirin users and suggest to have regular visual acuity and funduscopic examination.

Risks of newly onset hemorrhagic stroke in patients with neovascular age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) is an eye disease causing blindness in the elderly. It shares many common possible pathogenic mechanisms with cardiovascular diseases. Many studies have discussed the association between AMD and stroke, but the results were inconsistent. Our aim was to determine the associations between neovascular AMD and the risk of stroke in the Taiwanese population. METHODS: This is a retrospective cohort study. We used claims data from National Health Insurance Research Database. Patients aged more than 45 years without stroke, myocardial infarction, or any AMD were selected from 2001 to 2008 and followed until 2010. The index date was defined as the date of nAMD diagnosis (ICD-9 code, 362.52). The comparison group was patients without an nAMD diagnosis with age- and sex-matched to nAMD subjects at a ratio of up to 10 to 1. Kaplan-Meier survival analysis and Cox regression analysis were used. The incidence of stroke events (ICD-9 codes, 430-434) and their subtypes (hemorrhagic and ischemic) were primary outcomes. Secondary outcomes included acute myocardial infarction (AMI), composite AMI/stroke, and all-cause mortality. RESULTS: Patients with nAMD had a higher risk of developing stroke, with an adjusted HR of 1.30 (95% CI, 1.01-1.68). A higher risk for hemorrhagic stroke (HR, 1.70, 95% CI, 1.03-2.83) was also found. No significant differences were observed in ischemic stroke, the composite of AMI/stroke, and all-cause mortality. CONCLUSIONS: Patients with nAMD had a significantly higher risk of developing stroke, which was driven mainly by the increased risk of developing the hemorrhagic subtype.