Fenofibrate and diabetic retinopathy.

Background: Diabetic retinopathy (DR), a sight-threatening ocular complication of diabetes mellitus, is one of the main causes of blindness in the working-age population. Dyslipidemia is a potential risk factor for the development or worsening of DR, with conflicting evidence in epidemiological studies. Fenofibrate, an antihyperlipidemic agent, has lipid-modifying and pleiotropic (non-lipid) effects that may lessen the incidence of microvascular events. Methods: Relevant studies were identified through a PubMed/MEDLINE search spanning the last 20 years, using the broad term "diabetic retinopathy" and specific terms "fenofibrate" and "dyslipidemia". References cited in these studies were further examined to compile this mini-review. These pivotal investigations underwent meticulous scrutiny and synthesis, focusing on methodological approaches and clinical outcomes. Furthermore, we provided the main findings of the seminal studies in a table to enhance comprehension and comparison. Results: Growing evidence indicates that fenofibrate treatment slows DR advancement owing to its possible protective effects on the blood-retinal barrier. The protective attributes of fenofibrate against DR progression and development can be broadly classified into two categories: lipid-modifying effects and non-lipid-related (pleiotropic) effects. The lipid-modifying effect is mediated through peroxisome proliferator-activated receptor-α activation, while the pleiotropic effects involve the reduction in serum levels of C-reactive protein, fibrinogen, and pro-inflammatory markers, and improvement in flow-mediated dilatation. In patients with DR, the lipid-modifying effects of fenofibrate primarily involve a reduction in lipoprotein-associated phospholipase A2 levels and the upregulation of apolipoprotein A1 levels. These changes contribute to the anti-inflammatory and anti-angiogenic effects of fenofibrate. Fenofibrate elicits a diverse array of pleiotropic effects, including anti-apoptotic, antioxidant, anti-inflammatory, and anti-angiogenic properties, along with the indirect consequences of these effects. Two randomized controlled trials-the Fenofibrate Intervention and Event Lowering in Diabetes and Action to Control Cardiovascular Risk in Diabetes studies-noted that fenofibrate treatment protected against DR progression, independent of serum lipid levels. Conclusions: Fenofibrate, an oral antihyperlipidemic agent that is effective in decreasing DR progression, may reduce the number of patients who develop vision-threatening complications and require invasive treatment. Despite its proven protection against DR progression, fenofibrate treatment has not yet gained wide clinical acceptance in DR management. Ongoing and future clinical trials may clarify the role of fenofibrate treatment in DR management.

Erdafitinib-Induced Bilateral Multifocal Serous Retinal Detachments and Severe Dry Eye Related Unilateral Peripheral Ulcerative Keratitis in a Patient with Metastatic Urothelial Carcinoma.

Background: A case of bilateral multifocal serous retinal detachments and dry eye complicated with unilateral peripheral ulcerative keratitis (PUK) during erdafitinib therapy is described. Case description: A 76-year-old male underwent a baseline examination two months after initiating 8 mg erdafitinib therapy (April 2023) due to metastatic urothelial carcinoma. Left subfoveal serous retinal detachment was observed initially but the treatment was resumed as he was asymptomatic. In May 2023, bilateral multifocal subretinal fluid pockets were identified, and the patient was still asymptomatic. However, in June 2023 he complained of bilateral redness and a stinging sensation in his right eye. Bilateral severe dry eye and right PUK were diagnosed. He was prescribed dexamethasone eye drops and sodium hyaluronate artificial tears for both eyes. One week later corneal staining decreased, and progression of PUK ceased. Erdafitinib therapy was discontinued in June 2023 due to the planned transurethral prostatectomy. By July 2023, after discontinuation of the drug and administration of the topical treatment, the dry eye improved and the PUK became inactive. There was also resolution of subretinal fluid pockets in the right eye and a reduction of subretinal fluid pockets in the left eye. After the reinitiation of erdafitinib therapy, serous retinal detachments recurred in both eyes in September 2023, but both corneas remained stable with topical low-dose dexamethasone, cyclosporine-A and artificial tear usage. Conclusion: Erdafitinib therapy may lead to concurrent anterior and posterior segment complications. Multidisciplinary monitoring is crucial for patients undergoing erdafitinib therapy to prevent possible visual disturbances. LEARNING POINTS: Erdafitinib, a tyrosine kinase inhibitor of fibroblast growth factor receptors 1 to 4, is administered for the treatment of locally advanced, unresectable or metastatic urothelial carcinoma but however is fraught with several systemic and ocular side effects.Concurrent anterior and posterior segment ocular involvement could be encountered in patients undergoing erdafitinib therapy.Maintaining a high level of suspicion and closely monitoring for potential ocular complications through collaborative efforts is essential for all patients undergoing erdafitinib therapy.

Multimodal Imaging Characteristics and Diagnostic Value of Choroidal Nodules in Patients with Neurofibromatosis Type 1.

Objectives: Yasunari nodules are choroidal lesions observed in patients diagnosed with neurofibromatosis type 1 (NF-1) and characterized by relatively irregular dome-shaped, plaque-like, or patchy boundaries. The present study examines the multimodal imaging characteristics of Yasunari nodules and their value in the diagnosis of NF-1. Materials and Methods: Medical records including optical coherence tomography (OCT), enhanced depth imaging OCT, infrared reflectance (IR) imaging, OCT angiography, and color fundus images of NF-1 patients who were examined at the Department of Ophthalmology in Dokuz Eylül University Faculty of Medicine between January 2022 and December 2023 were retrospectively reviewed for the presence of Yasunari nodules. Results: A total of 54 eyes of 27 patients were included in the study. At least one choroidal nodule was detected on IR imaging in 52 eyes (96.3%). In 31 (72.1%) of the 43 eyes (79.6%) with available high-quality OCT angiography images, choroidal nodules were observed as areas showing a flow deficit in the choriocapillaris layer. Of the total 54 eyes included, Lisch nodules without choroidal nodules were observed in 2 eyes (3.7%). In 16 eyes (29.6%), Lisch nodules were not detected despite the presence of choroidal nodules. Both Lisch nodules and choroidal nodules were detected in the other 36 eyes (66.7%). Conclusion: Yasunari nodules are frequently observed in NF-1 cases and can be easily detected with multimodal imaging techniques, especially IR imaging. The ability to visualize choroidal nodules before the appearance of Lisch nodules demonstrates the importance of Yasunari nodules in the diagnosis of NF-1.

Endogenous Endophthalmitis Caused by Aspergillus lentulus in an Immunocompromised Patient with Lung Cancer

A 78-year-old man with a history of lung cancer, chemotherapy, radiotherapy, and coronavirus disease 2019 infection experienced visual deterioration of two-weeks' duration in his right eye. There was multifocal, yellowish-white retinitis foci, vascular engorgement, and scattered intraretinal hemorrhages extending from posterior pole to retinal periphery in the right eye, whereas the left eye was normal. Intravitreal vancomycin, ceftazidime, clindamycin, and dexamethasone were given for endogenous endophthalmitis initially. Vitreous culture confirmed the presence of Aspergillus lentulus, and he was treated with intravitreal amphotericin-B and voriconazole injections together with systemic amphotericin-B, voriconazole, posaconazole, and micafungin therapy. During follow-up, vitreoretinal surgery was performed because of rhegmatogenous retinal detachment, and he received one additional cycle of chemotherapy due to recurrence of the cancer. Although the retina was attached, enucleation was eventually required due to painful red eye. Atypical squamous cells beneath the neurosensory retina suggesting metastasis were noted on histopathological examination. Timely ocular examination is crucial for any immunocompromised patient having ocular symptoms. High level of suspicion for a fungal etiology is a must in these patients.

Ixabepilone related angiographically silent macular edema.

INTRODUCTION: We present a single-eyed case with a previous diagnosis of breast cancer who had intraretinal cystoid changes associated with the systemic administration of ixabepilone in her only seeing eye. To our best knowledge, this is the first reported case describing this phenomenon related to the ixabepilone administration. CASE DESCRIPTION: A 54-year-old woman with a history of breast cancer was examined due to visual deterioration in her only good left eye. The patient had undergone cataract surgery and lens implantation in her right eye following a childhood accident, but subsequently had developed a refractory glaucoma and lost her right vision. Six cycles of 40 mg/m2 systemic ixabepilone (3-hly intravenous infusion once every 3 weeks) had been administered within the past six months. Her visual decline started two weeks following the last treatment session. She was offered intravitreal anti-vascular endothelial growth factor injection elsewhere. Fluorescein angiogram showed no dye leakage whereas spectral-domain optical coherence tomography demonstrated parafoveal intraretinal cystoid changes. En-face optical coherence tomography revealed petaloid type roundish hyporeflective areas at the level of superficial and deep vascular plexus. Ixabepilone-associated cystoid maculopathy was suspected as she received only ixabepilone for the chemotherapy in the last six months. We thus recommended her not to continue ixabepilone therapy. Ten weeks after the ixabepilone cessation, intraretinal cystoid changes had resolved completely. CONCLUSION: Angiographically silent intraretinal cystoid changes may develop in association with the use of ixabepilone. Referral to an ophthalmologist should be considered for the patients experiencing visual complaints as ixabepilone cessation may lead to visual improvement and avoid unnecessary treatment.

Bartonella Henselae Related Unilateral Anterior Uveitis and Subsequent Multifocal Retinitis in a Case Under Certolizumab Treatment.

Introduction: A case of ocular bartonellosis under anti-tumour necrosis factor treatment is described. Case description: A 29-year-old woman with psoriasis who had been on certolizumab treatment was examined with a left visual deterioration following a fever bout, malaise, and placoid erythematous rashes on her neck. As there was acute anterior uveitis in her left eye, it was recommended to stop certolizumab treatment for a possible infectious aetiology. However, her physician elected to continue the certolizumab treatment. Ten days later, the patient noticed further visual decline despite the topical steroid treatment. This time, there were scattered yellow-white small retinitis foci at the left posterior pole. Infectious agents were searched and while Bartonella henselae antibodies were negative for immunoglobulin M, the immunoglobulin G titre was 1/80. Clinical findings were improved with the systemic treatment of oral trimethoprim-sulfamethoxazole (160/800 mg twice daily for six weeks) and azithromycin (500 mg once daily for two weeks). Discussion: Though extremely rare, ocular bartonellosis should be kept in mind in patients on anti-tumour necrosis factor treatment as rapid and accurate diagnosis may end up with an excellent visual outcome and full recovery. LEARNING POINTS: Anti-tumour necrosis factor treatment is fraught with several ocular side effects including myositis, corneal infiltrates, scleritis, uveitis, optic neuritis, retinal vasculitis and ophthalmoplegia.When a new uveitis episode occurs in cases undergoing anti-tumour necrosis factor therapy, its cause poses a diagnostic challenge as it can have either an infectious or a non-infectious nature.Though very rare, ocular bartonellosis may also occur in immunocompromised individuals and a prompt diagnosis and appropriate treatment can lead to an excellent visual recovery.

Active toxoplasma chorioretinitis in immunocompromised patients: a case series.

Toxoplasma chorioretinitis (TC) can exhibit atypical features in immunocompromised patients including bilaterality, extensive spread, multifocal presentation, large areas of retinal necrosis without adjacent retinal scarring, and diffuse necrotizing retinitis resembling the viral retinitis that may cause confusion in the differential diagnosis. The aim of this study was to present the clinical features of four eyes of three immunocompromised patients with active toxoplasma chorioretinitis. Two of the patients were female and one, male. Two patients had hematological malignancies and the remaining patient was under adalimumab treatment for ankylosing spondylitis. Visual complaints began 10 days to four months prior to TC diagnosis. All four eyes had mild-to-moderate anterior chamber cells together with severe vitritis on slit-lamp examination while there were solitary chorioretinitis lesions on fundoscopy. Despite all patients were negative for anti-toxoplasma immunoglobulin M, all were positive for immunoglobulin G. All three patients were successfully treated with a combined treatment of systemic and intravitreal anti-toxoplasmic drugs. Clinicians should be cautious for the possible toxoplasma chorioretinitis besides the other infectious entities when a new uveitis episode is detected in an immunosuppressed patient in order to avoid misdiagnosis and thereby wrong treatment.

Optical Coherence Tomography Angiographic Follow-Up in a Case of Subacute Sclerosing Panencephalitis and Unilateral Necrotising Retinitis.

We present a 20-year-old woman who was diagnosed with subacute sclerosing panencephalitis (SSPE) 20 months after presenting with unilateral retinitis. At presentation, the patient had two inferotemporal macular lesions in her left eye. Corresponding to these areas, optical coherence tomography (OCT) showed hyporeflective spaces with loss of nearly all of the retinal layers. OCT-angiography (OCTA) demonstrated some flow deficit areas with a reduction in the vessel density. Her serum measles antibody titre was high (IgG >5000.0 mIU/ml). Twenty months later the macular lesions had diminished in size, and there was some focal retinal thinning with interruption of the ellipsoid zone. OCTA showed that the flow deficit areas were diminished in size together with the relatively improved perfusion density. Neurological examination disclosed myoclonic jerks. Neuropsychological assessment demonstrated impaired executive function, attention, and narrowed lexical fluency. Measles IgG antibody was high in the cerebrospinal fluid (>230.0 U/ml). Brain magnetic resonance imaging demonstrated bilateral, non-specific, small foci of T2 hyperintensity in the frontoparietal subcortical white matter and centrum semiovale. The present case is the first where OCTA findings of SSPE-related retinal lesions have been described.

Embedded Episcleral Foreign Body Mimicking Nodular Anterior Scleritis.

A 56-year-old man was referred to our clinic for unilateral nodular scleritis unresponsive to systemic corticosteroids. A localized, nodular hyperemia on the nasal bulbar conjunctiva surrounding a central cyst-like lesion together with vascular engorgement was observed on slit-lamp examination of the left eye. No abnormal fundoscopic findings were noted. Surgical exploration revealed an embedded episcleral brown colored, soft to touch, splinter-like organic foreign body (FB) which was confirmed by the histopathological examination. Nodular hyperemia resolved during the postoperative follow-up period, and mild scar tissue accompanied by scleral thinning developed in the left nasal bulbar conjunctiva. Ocular injury associated with FBs may cause significant ocular morbidity depending on the nature and location of the FB. Severe visual disability may occur if left untreated. Subconjunctival FBs are rare and may present with a clinical picture mimicking episcleritis or scleritis. History of trauma involving a FB should always be assessed for an accurate differential diagnosis and appropriate management of patients with anterior scleritis.

Are intravitreal hyperreflective particles alike in eyes with acute toxoplasma chorioretinitis and non-infectious uveitis?

BACKGROUND: To compare distinctive features of hyperreflective particles observed on spectral-domain optical coherence tomography (OCT) sections in eyes with acute toxoplasma chorioretinitis (TC) and non-infectious uveitis (NIU). METHODS: Medical records and the spectral-domain OCT images of the patients with TC and NIU were retrospectively reviewed. The TC and NIU groups were compared in terms of age, sex, mean OCT image quality, mean central macular thickness (CMT), presence of intraretinal fluid (IRF), presence of subretinal fluid (SRF), number of hyperreflective particles in the posterior vitreous area and mean particle measurement in the posterior vitreous area. RESULTS: Non-infectious uveitis group included nine patients (60 %) with Behcet's uveitis, five patients (33.3 %) with idiopathic posterior uveitis or panuveitis, and the remaining patient (6.7 %) with HLA-B27 associated uveitis. Comparison of the mean age, sex distribution, mean OCT image quality, mean CMT, presence of IRF, presence of SRF and the mean number of hyperreflective particles in the posterior vitreous area between the two groups showed no statistically significant differences (p = 0.085, p = 0.051, p = 0.748, p = 0.431, p = 0.109, p = 0.080 and p = 0.152, respectively). However, the mean length of the hyperreflective particles in the posterior vitreous area was 27.22 ± 8.60 µm in the TC group, and 21.91 ± 3.58 µm in the NIU group, with a significant difference between the two groups (p = 0.036). CONCLUSION: This pilot study aimed to assess the hyperreflective particles in the posterior vitreous area using spectral-domain OCT images and image processing software. Despite its limitations, such as the small sample size, limited understanding of the nature of hyperreflective particles, and the absence of differentiation between acute and chronic uveitis, our study points out the potential role of the measurement of the hyperreflective particle length located in the posterior vitreous in differentiating the acute infectious versus non-infectious uveitis as the hyperreflective particles tend to be larger in infectious cases.

Presentation of Ocular Syphilis with Bilateral Optic Neuropathy.

A 60-year-old otherwise healthy male presented with a 1 year history of bilateral progressive visual loss. His best-corrected visual acuity was counting fingers at 2 m with his right eye and counting fingers at 0.5 m with his left eye. Visual field testing revealed bilateral near-total loss of visual fields. Slit-lamp examination was unremarkable, apart from bilateral grade two nuclear sclerotic cataracts. Both optic discs were pale-looking with some retinal pigment epithelial alterations at the left papillomacular region. Enhanced depth imaging optical coherence tomography depicted punctate hyperreflective dots at the inner choroidal level corresponding to the retinal pigment epithelial changes in the left eye. Fundus autofluorescence imaging revealed patchy hyper-autofluorescent and hypo-autofluorescent areas, and there was mild staining in the early and late phases of the fluorescein angiogram at the papillomacular region in the left eye. A diagnosis of bilateral optic neuropathy was made. A full systemic work-up was carried out, and serological tests pointed out the presence of syphilis with normal cranial magnetic resonance imaging. He was treated accordingly. Our case clearly demonstrates the importance of a high clinical suspicion for syphilis in cases of optic neuropathy.

The place of dexamethasone implant in patients with Vogt-Koyanagi-Harada disease who experienced systemic treatment-related hepatic dysfunction: A case series.

We presented our observation with dexamethasone (DEX) implant in six eyes of three patients with Vogt-Koyanagi-Harada (VKH) disease who experienced hepatic dysfunction due to the systemic immunosuppressive therapy during their follow-up. Three cases who could not continue with the azathioprine (AZA) or adalimumab (ADA) treatment due to elevated liver enzymes were given consecutive bilateral DEX implant injections during the follow-up. In the first case, oral AZA was discontinued due to an elevation of the liver enzymes at the 2nd month of AZA treatment, and then she received five bilateral DEX implant administrations during the follow-up of 61 months without any intraocular pressure rise or disease recurrence. The remaining two patients had an elevation of the liver enzymes when ADA treatment was added to the prophylactic isoniazid therapy and they each received three bilateral DEX implant administrations within a year again without any complications and disease recurrence. DEX implant can be a safe and effective alternative for individuals with VKH disease whose systemic treatment is ceased due to adverse effects of the systemic treatment and intravitreal therapy with DEX implant can be beneficial to achieve a recurrence-free follow-up.