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.

A Case of an Acute Zonal Occult Outer Retinopathy Variant Characterized With an Insidious Peripheral Onset and Centripetal Progression.

Acute zonal occult outer retinopathy (AZOOR) manifests as the rapid loss of one or multiple large zones of the outer retinal layers, often with a distinct sectoral distribution. Subtle fundus changes, such as pigmentary alterations around the optic nerve, are typically present in the early stages. Disease progression is characterized by the appearance of well-defined atrophic zones involving the outer retina, retinal pigment epithelium, and choroid. AZOOR lesions typically begin in the peripapillary region and then spread centrifugally toward the peripheral fundus. In this case report, we present the clinical and multimodal imaging characteristics of a 63-year-old woman with a symmetrical, peripheral-onset AZOOR variant with a very slow centrifugal progression. Most notably, the posterior pole was unaffected bilaterally.

Subretinal Drusenoid Deposits in a Patient With HELLP (Hemolysis, Elevated Liver Enzymes, Low Platelet) Syndrome.

Subretinal drusenoid deposits (SDD) are findings that can be observed in age-related macular degeneration as well as in ischemic ocular diseases. These deposits are believed to be of prognostic importance, as they have been shown to be associated with choroidal neovascularization. HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome is a condition linked with severe preeclampsia, and it presents ocular findings such as hypertensive retinopathy, serous retinal detachment, and cortical visual impairment. This case report discusses the presence and course of SDD in a female patient who presented with hypertensive retinochoroidopathy secondary to HELLP syndrome.

Isolated Inferior Division Oculomotor Nerve Palsy as the First Manifestation of Human Immunodeficiency Virus and Syphilis Co-Infection: A Rare Case Report.

Human immunodeficiency virus (HIV) and syphilis are two sexually transmitted diseases that continue to pose significant public health challenges globally. HIV and syphilis can be seen together; individuals with one of these infections are at risk of developing the other. Sharing common risk factors such as sexual transmission or intravenous drug use makes their coincidence likely. Syphilis, an infection caused by a spirochaete (Treponema pallidum), is a great mimicker and can present with a wide variety of clinical manifestations. Syphilis can cause various neurological symptoms including complete oculomotor nerve palsy; however, it is not a common manifestation. Here, we report for the first time a case of persistent incomplete oculomotor nerve palsy with pupillary involvement caused by the involvement of the inferior division of the oculomotor nerve, secondary to HIV and syphilis co-infection.

Choroidal, retinal, and optic nerve changes in rheumatoid arthritis and primary sjogren's syndrome patients: comparison with each other and healthy subjects.

PURPOSE: The present study aims to evaluate the optic nerve, macula, and choroidal changes in both rheumatoid arthritis (RA) and primary Sjögren's syndrome (SjS) patients, and to compare these findings with age-matched healthy volunteers. METHODS: This study included 46 RA patients, 33 primary SjS patients, and 37 age-matched healthy volunteers. All of the patients underwent a thorough ophthalmological examination, during which measurements of the retinal nerve fiber layer (RNFL), ganglion cell layer(GCL), and subfoveal choroidal thickness (CT) were taken using OCT (optical coherence tomography). The measurements taken from the right eye of each patient were used to compare among the groups. RESULTS: RNFL thickness in superior quadrant was found to be statistically significantly thinner in the eyes with RA when compared to the control group (p = 0.022). In the nasal quadrant, the RNFL thickness was significantly thinner in patients with primary SjS compared to healthy individuals (p = 0.036). Also, the temporal quadrant RNFL was significantly thinner in RA patients than in the primary SjS patients (p = 0.033). GCL thickness was observed to be thinner in all quadrants of both RA and primary SjS groups compared to the control group. However, the difference was not found to be statistically significant. Subfoveal CT was observed to be thicker in RA and SjS groups compared to the control group, but this difference was also not statistically significant. CONCLUSION: Systemic autoimmune diseases like RA and primary SjS can lead to a decrease in RNLF and GCL thickness, which can impair visual acuity even in the absence of ocular symptoms. Therefore, monitoring changes in the optic nerve, retina, and choroid layer are crucial in these patients.

Could a Gout Attack Cause Non-Arteritic Anterior Ischaemic Optic Neuropathy?

Non-arteritic anterior ischaemic optic neuropathy (NAION) is a common cause of optic neuropathy in individuals over the age of 50. While risk factors such as hypertension, diabetes, and hyperlipidaemia have been identified, recent literature suggests that new risk factors may be associated with NAION. This article reports a case of NAION that occurred concurrently with an acute gout attack in a 78-year-old male patient with no other systemic diseases. We suggest that gout may be a new potential risk factor for NAION as it has the potential to cause inflammation and vascular dysfunction, particularly during acute attacks. The case emphasises the importance of considering gout as a possible risk factor in the aetiology of NAION.

Bilateral Sequential Non-Arteritic Anterior Ischemic Optic Neuropathy Following COVID-19 Infection: A Rare Case Report.

To report a patient with bilateral sequential non-arteritic anterior ischemic optic neuropathy (NA-AION) following severe COVID-19 infection. A 50-year-old male patient reported a 1-week history of painless vision loss in the right eye in additon to complaining of blurred vision in the left eye 4 weeks earlier. He had tested COVID-19 positive 4 weeks before the onset of symptoms in his left eye. Further investigations revealed that the most possible cause of vision loss was NA-AION associated with COVID-19. COVID-19 infection may be responsible for NA-AION. Therefore, ophthalmologists should keep this infection in mind when systemic investigation for the underlying etiology of NA-AION.

A Rare Case Report of Eight Syndrome Secondary to Syringomyelia Associated with Type I Chiari Malformation.

Eight syndrome is defined as the combination of a unilateral conjugate gaze palsy and ipsilateral seventh cranial nerve palsy. It may occur as a result of demyelinating, vascular, infectious, or compressive lesions of the brainstem localized to the caudal pontine tegmentum. A 43-year-old woman was admitted to our clinic with complaints of headache, inability to look to the left, and weakness on the left side of her face. The complaints had begun abruptly about a month before her admission. Suboccipital decompression surgery for type I Chiari malformation had been performed 10 years earlier. Neuro-ophthalmological examination revealed left-sided horizontal gaze palsy and anisocoria. Cranial and cervical magnetic resonance images revealed cerebellar tonsillar herniation and syringomyelia, the latter of which was considered to be the cause of eight syndrome. No interventions were performed, and periodic follow-up was advised on neurosurgical consultation. Left gaze palsy and facial palsy recovered almost completely in three months, while the anisocoria persisted. Syringomyelia should be considered among the causes of horizontal gaze palsy plus ipsilateral seventh nerve palsy, termed as eight syndrome. Clinical suspicion and appropriate radiological examination can aid in the diagnosis.

Sphenoid Bone Dysplasia: A Rare Cause of Compressive Optic Neuropathy Mimicking Glaucoma.

Fibrous dysplasia is a benign, rare bone disease in which bone is replaced by fibro-osseous tissue to varying degrees. It can present differently depending on the amount of compression caused by the fibro-osseous tissue. Patients are usually asymptomatic, but symptoms related to cranial nerve compression may occur. In this case report, we describe a 45-year-old woman with sphenoid bone dysplasia which compressed the optic nerve and caused unilateral optic disc cupping that mimicked glaucoma. Our case highlights the importance of including compressive etiologies associated with optic disc cupping in the differential diagnosis of glaucoma.

Real-life outcomes of intravitreal ranibizumab, aflibercept, and dexamethasone implant administrations in patients with treatment-naïve diabetic macular edema.

PURPOSE: To investigate optical coherence tomography (OCT) biomarker data on visual recovery in treatment-naïve diabetic macular edema (DME) and follow the results of intravitreal ranibizumab (RNB), aflibercept (AFL), and dexamethasone (DEX) implant administration within the 1st year of the pro re nata treatment regimen. METHODS: One hundred and twenty eyes of 102 patients were enrolled in the study. The patients medical records were analyzed retrospectively. Best-corrected visual acuity (BCVA), central macular thickness (CMT), type of DME, presence of subretinal fluid, number and localization of hyperreflective dots, vitreomacular interface disorders, disorganization of the retinal inner layer (DRIL), inner segment/outer segment (IS/OS) junction-external limiting membrane (ELM) status, intraretinal cyst diameter and localization, and subfoveal choroidal thickness were examined in all patients. RESULTS: A statistically significant increase in BCVA and a decrease in CMT were detected in all treatment groups. When cases were evaluated in terms of BCVA before and after treatment, statistically significant differences were observed in the RNB and AFL groups at 1 and 4 months and in the DEX group during the 1st year. In terms of OCT biomarkers, visual recovery was obtained in cases of intact IS/OS-ELM and non-DRIL patients. In the serous macular detachment group, more visual gain was achieved with the RNB (1 and 4 months) and AFL (1, 4, and 6 months) agents compared to the DEX implant. On the other hand, in the group with cystoid macular edema, more visual gain was achieved with RNB compared to the DEX implant in all months, but more visual gain was achieved only in the 1st month with AFL administration. CONCLUSION: Significant improvement was achieved for both BCVA and CMT in all treatment groups. We expect that OCT-based prognostic factors will become more important in the treatment of DME and will be determining factors in the choice of treatment.

The evaluation of patient demographics, etiologies and apraclonidine test results in adult Horner's syndrome.

PURPOSE: We aimed to demonstrate the patient demographics, etiologies and apraclonidine test results in adult Horner's syndrome. METHODS: This retrospective study was performed by the analysis of medical data of patients who were given 0.5% apraclonidine test. Patients' past medical history, demographic data, etiologies, accompanying neurological findings and pharmacological test results were assessed. RESULTS: Forty patients (21 females and 19 males) with a mean age of 50.3 ± 11.6 years were evaluated. Apraclonidine 0.5% test was positive in 37 patients (92.5%). An etiology could be identified in 20 patients (central [9 patients, 45%], preganglionic [9 patients, 45%] and postganglionic [2 patients, 10%]). Neurological findings accompanying Horner's syndrome were present in 8 patients. CONCLUSION: Despite detailed investigations, in a significant number of patients with Horner's syndrome an underlying cause may not be detected. Among the identifiable lesions, central and preganglionic involvements are still the first leading causes of Horner's syndrome. In addition, apraclonidine test may not be positive in all patients and a negative response does not exclude Horner's syndrome.

Posterior Segment Manifestations of Cat-scratch Disease: A Mini-review of the Clinical and Multi-modal Imaging Features.

Bartonella henselae, an intracellular gram-negative bacillus, is usually transmitted from infected cats to humans by direct or indirect contact. The bacterium mainly infects erythrocytes and endothelial cells thereby leading to so called cat-scratch disease (CSD) and may present with various localised and/or systemic manifestations. The eye is the most commonly affected organ in disseminated CSD and ocular bartonellosis has been reported in 5-10% of CSD patients. The most well-known clinical feature of ocular bartonellosis is neuroretinitis but various sight-threatening posterior segment lesions involving the optic nerve, retinal vasculature, retinal and choroidal tissues may occur during the disease course. This mini-review aims to overview both the clinical and multi-modal imaging characteristics of posterior ocular segment manifestations of CSD.

Bilateral Optic Neuropathy Revealing Chronic Hepatitis B Infection: A Report of A Rare Case.

Hepatitis B virus (HBV) infection is a major public health problem. Liver diseases such as cirrhosis and hepatocellular carcinoma are the main causes of mortality and morbidity associated with this viral infection. Ocular manifestations may also arise during the course of HBV infection. We herein present a 44-year-old male with bilateral optic neuropathy revealing chronic HBV infection.

Optic Nerve Tortuosity in Neurofibromatosis Type 1: A Rare Case Report.

Optic nerve tortuosity is a benign and usually asymptomatic optic nerve abnormality documented on magnetic resonance imaging. This abnormality has rarely been defined in neurofibromatosis type 1 (NF1) cases. In this case report, we present incidental optic nerve tortuosity in a housewife with NF1 without any ocular involvement. Optic nerve tortuosity may occasionally be an incidental finding in patients with NF1. Therefore, clinicians should be aware of this rare coexistence.

Place of intravitreal dexamethasone implant in the treatment armamentarium of diabetic macular edema.

Diabetic macular edema (DME) is a very important and well-known cause of visual loss in diabetics. Blood-retina barrier disruption and consequent intraretinal fluid accumulation may lead to retinal thickening at the posterior pole namely DME. Even though it is not clearly understood, current evidence suggests that chronic low-grade inflammation characterized with various cytokines has a major role in the occurrence of DME. Clinical trials are continuously shaping our treatment approaches for the eyes with DME. Today, vascular endothelial growth factor (VEGF) inhibitor and steroid administrations are the main alternatives in DME treatment. Dexamethasone (DEX) implant (Ozurdex ®; Allergan, Inc., Irvine, CA, United States) was approved by the United States Food & Drug Administration in 2014 for DME treatment. The implant is made up of a biodegradable solid copolymer that is broken down by releasing its active ingredient into the vitreous cavity over time. Biphasic release feature of this sustained-release drug delivery system ensures its efficacy for up to 6 mo with an acceptable and manageable safety profile. DEX implant provides a favorable anatomical and functional outcome in DME as shown in several randomized-controlled studies but has a relatively higher ocular side-effect profile such as increased risk of cataract formation and raised intraocular pressure when compared to the gold standard anti-VEGF agents. Thus, DEX implant becomes the second-line treatment option demonstrating inadequate clinical response to anti-VEGF therapy. However, it can be preferred as the first-line treatment in vitrectomized and pseudophakic eyes. Even in some selected conditions DEX implant is favored over anti-VEGF agents where the use of VEGF-inhibitors is either inappropriate or contraindicated such as the patients with a recent history of a major cardiovascular or cerebrovascular event, pregnancy and noncompliant to frequent visits. This mini-review briefly overviews the efficacy, safety profile and complications of DEX implant and summarizes the outcome of DEX implant administration in major clinical studies on DME treatment.

En face optical coherence tomography patterns in patients with angiographically documented uveitic macular edema: a cross-sectional retrospective study.

PURPOSE: To elucidate the en face optical coherence tomography (OCT) patterns of macular edema in eyes with angiographically documented uveitic macular edema (UME) and compare visual acuity (VA), OCT and OCT-angiography (OCT-A) parameters among the morphological subgroups. METHODS: Thirty-nine eyes of 29 patients with angiographically proven UME were enrolled into the study. All patients underwent comprehensive ophthalmological examination including structural OCT and OCT-A in addition to fluorescein angiography. Eyes with UME were divided into three subgroups (petaloid, sunflower and spoke-wheel pattern) with the help of en face OCT imaging. RESULTS: Posterior uveitis was the most common type of uveitis (17 patients; 58.7%), followed by panuveitis (11 patients; 37.9%) and then intermediate uveitis (1 patient; 3.4%). Underlying causes of uveitis were Behçet's disease (13 patients; 44.8%), idiopathic (11 patients; 37.9%), rheumatoid arthritis (2 patients; 6.9%), sarcoidosis (1 patient; 3.4%), inflammatory polyarthritis (1 patient; 3.4%) and psoriatic arthritis (1 patient; 3.4%). The most common en face OCT pattern was petaloid type (25 of 39 eyes; 64.1%). Eleven eyes (28.2%) had sunflower pattern and three (7.7%) spoke-wheel pattern. There were no statistically significant difference among the subgroups regarding the age, VA, central macular thickness and vessel density. CONCLUSION: This study reveals three morphological en face OCT patterns in eyes with UME and en face OCT may find a niche in the UME classification with the accumulation of experience among the uveitis experts.

Assessment of Optical Coherence Tomography Findings in Adults with Attention Deficit Hyperactivity Disorder: A Case-Control Study.

Background: To assess retinal nerve fiber layer and ganglion cell-inner plexiform layer thickness using optical coherence tomography in attention deficit hyperactivity disorder adults on regular methylphenidate treatment, comparing them to healthy controls. Methods: A total of 33 attention deficit hyperactivity disorder adults and 31 healthy subjects, matched for age, gender, and education (control group), were included in this study. Retinal nerve fiber layer and ganglion cell-inner plexiform layer thickness of both eyes were measured using optical coherence tomography, and symptom severity was evaluated using Adult Attention Deficit Hyperactivity Disorder Self-Report Scale and Wender Utah Rating Scale. Results: There was no significant difference in retinal nerve fiber layer thickness between the attention deficit hyperactivity disorder and control groups (P > .05). Thinner ganglion cell-inner plexiform layer total (P = .044), inferior (P = .012), and inferior nasal quadrant thickness (P = .049) were observed in attention deficit hyperactivity disorder patients as compared to the controls. Conclusion: Findings detected thinner ganglion cell-inner plexiform layer in some quadrants of attention deficit hyperactivity disorder adults, indicating an early disorder in retinal structure development. Whether retinal structures are sensitive attention deficit hyperactivity disorder biomarkers should be supported and investigated in future multimodal studies.

Bilateral Congenital Prepapillary Retinal Arterial Loop.

Prepapillary vascular loops are rare congenital vascular abnormalities of the retinal vasculature. This mostly benign condition can sometimes cause complications such as branch retinal artery occlusion and vitreous haemorrhage. Disc collaterals, neovascularisation of the optic disc, idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) syndrome and Wyburn Mason syndrome should be kept in mind for the vascular differential diagnosis. In addition, when the loops present bilaterally and settle into the region adjacent to the optic disc border, they can be misdiagnosed as papilloedema. The diagnosis is usually made clinically by careful fundus examination. Optical coherence tomography and fundus fluorescein angiography might serve as ancillary tools for the diagnosis. In this report, we present a 52-year-old male with bilateral prepapillary arterial loops referred to our clinic with a preliminary diagnosis of papilloedema.

Inflammatory Choroidal Neovascular Membranes in Patients With Noninfectious Uveitis: The Place of Intravitreal Anti-VEGF Therapy.

Inflammatory choroidal neovascularization (iCNV) is an infrequent but an important cause of visual morbidity in patients with non-infectious uveitis and mostly occurs in intermediate or posterior uveitis. Punctate inner choroiditis, Vogt-Koyanagi-Harada disease and multifocal choroiditis are among the leading causes of uveitis entities resulting in iCNVs. The diagnosis and management of iCNVs still remain a challenge. Use of multimodal imaging techniques such as fluorescein angiography, indocyanine green angiography, optical coherence tomography (OCT) and OCT-angiography may be necessary for the diagnosis of iCNVs. The treatment algorithm is not straightforward for iCNV. While control of the active inflammation with steroids and/or immunosuppressive agents is a key to success, various adjunctive treatment modalities such as thermal laser photocoagulation, photodynamic therapy and surgical membrane removal were also co-administered previously. Nowadays, vascular endothelial growth factor (VEGF) inhibitors have become the most commonly administered adjunctive treatment option as they provide better anatomical and functional outcome and the recurrence rate of CNV is relatively low. We hereby reviewed important clinical studies and case series on anti-VEGF administration in iCNVs and briefly overviewed their results.

Simultaneous Cataract, Maculopathy and Optic Atrophy Secondary to High-Voltage Electrical Shock Injury.

A 32-year-old man presented to our clinic with complaint of vision loss in both eyes (oculus utro; OU). Past medical history revealed that he had been exposed to high-voltage electrical current that passed through the temporal region of the head 2 months ago. Slit-lamp examination demonstrated cortico-nuclear cataract and mature cataract in his right eye (oculus dexter; OD) and left eye (oculus sinister; OS), respectively. On fundus examination, a macular hole was observed in OD. Optic atrophy and foveal atrophy were observed in the left fundus examination after cataract surgery. Simultaneous cataract, maculopathy and optic atrophy may occur after high-voltage electrical current injury. Therefore, clinicians should perform detailed anterior and posterior segment examinations in such patients.