Axenfeld-Rieger syndrome: more than meets the eye.

BACKGROUND: Axenfeld-Rieger syndrome (ARS) is characterised by typical anterior segment anomalies, with or without systemic features. The discovery of causative genes identified ARS subtypes with distinct phenotypes, but our understanding is incomplete, complicated by the rarity of the condition. METHODS: Genetic and phenotypic characterisation of the largest reported ARS cohort through comprehensive genetic and clinical data analyses. RESULTS: 128 individuals with causative variants in PITX2 or FOXC1, including 81 new cases, were investigated. Ocular anomalies showed significant overlap but with broader variability and earlier onset of glaucoma for FOXC1-related ARS. Systemic anomalies were seen in all individuals with PITX2-related ARS and the majority of those with FOXC1-related ARS. PITX2-related ARS demonstrated typical umbilical anomalies and dental microdontia/hypodontia/oligodontia, along with a novel high rate of Meckel diverticulum. FOXC1-related ARS exhibited characteristic hearing loss and congenital heart defects as well as previously unrecognised phenotypes of dental enamel hypoplasia and/or crowding, a range of skeletal and joint anomalies, hypotonia/early delay and feeding disorders with structural oesophageal anomalies in some. Brain imaging revealed highly penetrant white matter hyperintensities, colpocephaly/ventriculomegaly and frequent arachnoid cysts. The expanded phenotype of FOXC1-related ARS identified here was found to fully overlap features of De Hauwere syndrome. The results were used to generate gene-specific management plans for the two types of ARS. CONCLUSION: Since clinical features of ARS vary significantly based on the affected gene, it is critical that families are provided with a gene-specific diagnosis, PITX2-related ARS or FOXC1-related ARS. De Hauwere syndrome is proposed to be a FOXC1opathy.

Orbital Fibrotic Band as Cause of Monocular Elevation Deficiency.

Monocular elevation deficiency is a congenital, unilateral inability of elevation. It is classified as innervational, restrictive, or combine types. Here, we report a rare case of monocular elevation deficiency who had 60 PD left hypotropia and left ptosis with limited elevation (-5) both on abduction and adduction. Orbital MRI revealed a hypointense fibrotic band between the superior oblique and superior rectus muscles extending obliquely in the superonasal direction between the sclera and orbital roof. She was successfully treated after severing the fibrotic band between the sclera and bony orbit.

Evaluation of fixation characteristics in amblyopia using microperimetry.

PURPOSE: To evaluate fixation characteristics in amblyopia using macular analyzer integrity assessment (MAIA) microperimetry and to investigate the factors affecting fixation stability. METHODS: This prospective, cross-sectional study enrolled a total of 58 amblyopic patients who were between 8 and 55 years old. Average threshold macular sensitivity (AT) and fixation characteristics were assessed using MAIA microperimetry. Two Bivariate contour ellipse area (BCEA) fixation indices (63% and 95% proportional values) and the percentage of fixation points within 1° and 2° from the fovea (P1 and P2) were used to assess fixation stability. Non-amblyopic fellow eyes were used as the control group for comparison. RESULTS: AT and fixation stability indices (P1, P2, BCEA 63%, BCEA 95%) were worse in the amblyopic eyes than in the fellow eyes (p < 0.05, for all indices). There was a moderate positive correlation between best corrected visual acuity (BCVA), and AT, and P2, and a moderate negative correlation between BCVA, and BCEA indices. 48% of the eyes were eccentrically fixating (the percentage was 25% in the anisometropic group, 52% in the strabismic group, and 69% in the combined group) and 32% in the non-amblyopic eye (p = 0.052). The preferred fixation eccentricity in amblyopic eyes was significantly greater than the non-amblyopic eyes (p = 0.004), and there was a negative correlation between preferred fixation eccentricity and BCVA (p = 0.012, r = - 0.327). CONCLUSIONS: Our data showed a decrease in fixation stability, a positive correlation between fixation stability and BCVA, and a negative correlation between preferred fixation eccentricity and BCVA in amblyopic eyes.

Diplopia After Migraine Surgery.

A 46-year-old man with refractory migraine headache was treated with decompressive migraine surgery of the supraorbital and supratrochlear nerves. Postoperatively, he reported diplopia that got better on left head tilt. After ophthalmological examination, a diagnosis of right superior oblique palsy was made. The aim is to report the first case of superior oblique muscle or trochlea damage that may have occurred because of inadvertent entry through the orbital septum into the right superior orbit.

Evaluation of retinal vessel density and choriocapillaris flow in migraine patients with and without aura.

PURPOSE: Migraine is thought to be a neurovascular disorder and increases the likelyhood to develop ischemic complications. Studies have shown that vascular disorders such as ischemic optic neuropathy, retinal artery and vein obstructions are more common in patients with migraine. This study aimed to evaluate the differences between retinal and optic disc microvasculature between migraine patients with and without aura and healthy controls using optical coherence tomography angiography (OCTA) imaging. METHODS: Thirty-three patients with migraine and 28 healthy subjects were included in this prospective cross sectional study. Optical coherence tomography angiography imaging was performed for the macula and optic disc. Vessel densities (VD) and choriocapillaris flow values were compared between three groups: control group, migraine with aura (MWA), and migraine without aura (MWOA). RESULTS: There was no difference between the three groups for the VDs of the foveal, perifoveal, parafoveal, and the whole area. The choriocapillaris flow of patients with MWA was significantly less than that of the MWOA and control groups. The VDs of the optic disc revealed no significant difference between the three groups. CONCLUSION: A lack of choriocapillaris autoregulatory mechanisms may be a possible cause of the decrease in choriocapillaris flow in patients with MWA.

Ocular vascular changes during pregnancy: an optical coherence tomography angiography study.

BACKGROUND: Pregnancy is a period presenting with many physiological adaptation mechanisms. One of the structures in which these mechanisms are observed is ocular tissues. The cornea, lacrimal and meibomian glands, and chorioretinal complex are all among the structures affected by changes during pregnancy. In this study we aimed to evaluate the macular and optic disc vessel density (VD) changes by Optical Coherence Tomography Angiography (OCTA) imaging in pregnancy. METHODS: A total of 248 eyes from 124 pregnant women and 80 eyes from 40 healthy control women were involved. Vessel densities of macula were evaluated for superficial capillary plexus (SCP) and deep capillary plexus (DCP) in whole macula, foveal, parafoveal and perifoveal region. Peripapillary and whole optic disc VDs were also evaluated. Vessel densities of macula and optic disc were compared between control individuals and pregnant women. Vessel densities in different trimesters were also evaluated. RESULTS: Modest but significant differences in VDs of whole macula of SCP and DCP were observed in pregnancy group. Additionally, perifoveal and parafoveal region of SCP, whole disc and radial peripapillary capillary VD were significantly higher in pregnancy group. There was no correlation between VD ratios of macula and optic disc and pregnancy weeks and trimesters. CONCLUSIONS: This is the first study focusing on the OCTA parameters in pregnant individuals. These findings suggest that physiological changes during pregnancy are not limited to the cornea, eyelids and the choroid but also to the retinal and optic disc vasculature.

Peripapillary Vessel Density Measured by Optical Coherence Tomography Angiography in Idiopathic Intracranial Hypertension.

BACKGROUND: Although alterations in the peripapillary retinal nerve fiber layer (RNFL) in patients with idiopathic intracranial hypertension (IIH) have been characterized using optical coherence tomography (OCT), there are little data regarding the peripapillary vasculature in this patient population. Our aim was to evaluate findings of OCT angiography (OCT-A) in the peripapillary region in addition to the RNFL measurements on OCT in patients with IIH. METHODS: Thirty-eight eyes of 19 patients with IIH and 42 eyes of 21 healthy controls were enrolled in our study. Papilledema was graded according to the Frisen scale. Peripapillary RNFL and vessel density were evaluated with OCT and OCT-A, respectively. RESULTS: RNFL thickness was found to be increased with OCT, but this was statistically significant only in the inferior location in IIH patients when compared with the control group. There was a significant decrease in mean peripapillary vessel density measured with OCT-A in IIH patients with papilledema when compared with the control group (P < 0.05). CONCLUSIONS: In patients with IIH, there was a decrease in peripapillary vessel density measured by OCT-A, and this decrease may be a consequence of the swelling of axons in the peripapillary retina due to papilledema. However, autoregulatory vascular mechanisms may also play a role in decreased peripapillary vessel density.

Comparison of Spot Vision Screener and Tabletop Autorefractometer with Retinoscopy in the Pediatric Population.

Objectives: Determining the accuracy of cycloplegic refractive error measurements made with the Spot Vision Screener (SVS, Welch Allyn Inc, Skaneateles Falls, NY, USA) is important for refractive assessment of uncooperative patients during optometric examinations. This study compared cycloplegic refractive errors measured by SVS and tabletop autorefractometer to cycloplegic retinoscopy in children. Materials and Methods: Eighty-eight eyes of 44 subjects were examined in the study. Refractive error measurements were obtained under cycloplegia using retinoscopy, SVS, and Nidek ARK-530 tabletop autorefractometer (ARK-530, Nidek, Japan). Spherical and cylindrical values, spherical equivalents (SE), and Jackson cross-cylinder values at axes of 0° (J0) and 45° (J45) were recorded. Correlations between methods were analyzed using intraclass correlation coefficient (ICC) and Bland-Altman analysis. Results: The mean age was 7 years (range: 6 months-17 years). Sixteen (36%) of the subjects were female and 28 (64%) were male. For SE there was excellent agreement between retinoscopy and SVS (ICC: 0.924) and between retinoscopy and tabletop autorefractometer (ICC: 0.995). While there was a moderate correlation between retinoscopy and SVS for cylindrical values (ICC: 0.686), excellent correlation was detected between retinoscopy and autorefractometer (ICC: 0.966). J0 and J45 crosscylinder power values were not correlated between retinoscopy and SVS (ICC: 0.472) or retinoscopy and tabletop autorefractometer (ICC: 0.442). Retinoscopy was correlated with both SVS and tabletop autorefractometer for all parameters within ±1.96 standard deviations in Bland-Altman analysis. Conclusion: Cycloplegic retinoscopy is the gold standard for refractive error measurement in the pediatric population. However, it requires time and experienced professionals. This study revealed moderate to good agreement between SVS and retinoscopy, with better agreement in spherical errors than cylindrical errors. Although the SVS is intended for screening programs, it may also be useful in the pediatric eye office to estimate spherical refractive error in uncooperative patients.

Histopathological findings of anterior lens capsule in pediatric cataract.

PURPOSE: To investigate the histopathological findings of the anterior lens capsule in pediatric patients who had surgery for cataracts. METHODS: This study is a prospective interventional study. Anterior capsule tissue samples that were obtained by the anterior capsulotomy method during phacoemulsification surgery were fixed and examined under a transmission electron microscope. RESULTS: Twenty-two eyes of 19 patients who were diagnosed with congenital and juvenile cataracts were included in this study. Five patients had associated systemic diseases, including hydrocephalus, cerebral palsy, prematurity, juvenile myelomonocytic leukemia, and Down's syndrome. Electron microscopic evaluation demonstrated single-layered epithelium under the capsule, degenerated organelles with round-oval and prismatic-oval nuclei, and degenerated mitochondria and heterochromatin-rich nuclei. In the case with cerebral palsy, collagen fibrils of the connective tissue and fibroblast-like cells were observed replacing the epithelium that should be underneath the capsule in both eyes, and there was a disorganized distribution of collagen fibrils and vacuole structures in the cytoplasm of fibroblast-like cells. CONCLUSION: Similar histopathological findings were found in pediatric cataracts with or without systemic disease except in one cerebral palsy case. The absence of lens epithelium may have been a result of degeneration in this patient, and this can be attributed to the presence of systemic inflammation and gliosis in cerebral palsy. The absence of lens epithelium can play a role in the development of dense subcapsular fibrosis and cataract formation.

Reappearance of excentric persistent fetal vasculature stalk following laser treatment in a patient with type 1 retinopathy of prematurity.

PURPOSE: In this report, we aim to present an unusual reappearance of hyaloidal artery remnant with atypical localization during the follow-up of an infant who underwent indirect laser photocoagulation for type 1 ROP. METHODS: Retrospective case report. RESULTS: We report a case of reappearance of an eccentrically located hyaloidal stalk in the macular area during the follow-up period, 2 weeks after laser photocoagulation for type 1 ROP subsequently progressed to cause foveal distortion, which is successfully removed with a lens-sparing vitrectomy. CONCLUSIONS: To the best of our knowledge, there is no similar case in the literature. In the presence of fibrovascular proliferation extending into the vitreous, especially in premature infants, it should be kept in mind that this may be a reappearance of PFV and it may not always be located on the optic disc.

Accommodation Paralysis after Pheniramine Maleate Injection: A Case Report.

We present a case in which Gilbert syndrome was diagnosed following a neuro-ophthalmic complaint. Adverse effects of drugs as well as various systemic, neurological, and local ocular pathologies can cause accommodative insufficiency and loss of accommodation. A 29-year-old man was admitted to an ophthalmology department with blurred vision and diagnosed as suffering from acute accommodation paralysis. He had a history of being given a pheniramine maleate injection for pruritus 20 days previously. Symptoms began immediately following the injection. After systemic evaluation and laboratory tests, he was diagnosed as having Gilbert syndrome. His complaints and symptoms recovered in approximately a further 10 days. Metabolism of pheniramine maleate can be impaired in Gilbert syndrome and anticholinergic effects can cause accommodation paralysis.

Chromatographic Analysis of Aqueous Humor of Bupivacaine in Different Administration Approaches.

Different administration approaches were investigated for the selection of bupivacaine administration type and a sensitive high-performance liquid chromatographic (HPLC) method has been developed. Developed method was validated and applied for the determination of bupivacaine in rabbit aqueous humor. The separation was achieved using a XTerra, C8 (250 × 8 mm i.d., particle size 5 µm) analytical column with a mobile phase consisted of acetonitrile and sodium dihydrogen phosphate (pH = 3.0, 20 mM; 30:70, v/v). Bupivacaine detection was performed by Diode Array detector (DAD) at 220 nm. The retention times for bupivacaine is 15.886 min. HPLC-DAD method was linear in the range of 75-4000 ng/mL. The limit of detection was 25 ng/mL and the limit of quantification of bupivacaine was found to be 75 ng/mL (relative standard deviation, RSD ≤ 15%, n = 6). In intra-day and inter-day precision and accuracy analysis, the RSD was found to be in the range of 0.96 and 7.98%, the bias values were 0.64 and 3.33%. Method was carried out for three different type of bupivacaine application because of the investigation of effective drug administration. Twenty aqueous humor samples were in the range of 0.642 and 5.124 µg/mL.

Distinct Roles of Histone Lysine Demethylases and Methyltransferases in Developmental Eye Disease.

Histone lysine methyltransferase and demethylase enzymes play a central role in chromatin organization and gene expression through the dynamic regulation of histone lysine methylation. Consistent with this, genes encoding for histone lysine methyltransferases (KMTs) and demethylases (KDMs) are involved in complex human syndromes, termed congenital regulopathies. In this report, we present several lines of evidence for the involvement of these genes in developmental ocular phenotypes, suggesting that individuals with structural eye defects, especially when accompanied by craniofacial, neurodevelopmental and growth abnormalities, should be examined for possible variants in these genes. We identified nine heterozygous damaging genetic variants in KMT2D (5) and four other histone lysine methyltransferases/demethylases (KMT2C, SETD1A/KMT2F, KDM6A and KDM5C) in unrelated families affected with developmental eye disease, such as Peters anomaly, sclerocornea, Axenfeld-Rieger spectrum, microphthalmia and coloboma. Two families were clinically diagnosed with Axenfeld-Rieger syndrome and two were diagnosed with Peters plus-like syndrome; others received no specific diagnosis prior to genetic testing. All nine alleles were novel and five of them occurred de novo; five variants resulted in premature truncation, three were missense changes and one was an in-frame deletion/insertion; and seven variants were categorized as pathogenic or likely pathogenic and two were variants of uncertain significance. This study expands the phenotypic spectra associated with KMT and KDM factors and highlights the importance of genetic testing for correct clinical diagnosis.

Cataract surgical training in Europe: European Board of Ophthalmology survey.

PURPOSE: To survey recently graduated European ophthalmologists concerning cataract surgery (CS) training opportunities. SETTING: Countries affiliated to the European Board of Ophthalmology (EBO). DESIGN: Cross-sectional study of anonymous survey results. METHODS: A 23-question online survey was emailed to candidates who sat the EBO Diploma Examination as residents between 2018 and 2022. RESULTS: 821 ophthalmologists from 30 countries completed the survey. The mean residency duration was 4.73 (SD 0.9) years. The mean reported number of entire CS procedures performed was 80.7 (SD 100.6) at the end of residency, but more than 25% of respondents (n = 210) had received no live CS training during their residency. The self-confidence (scale, 1 to 10) to perform a simple case or challenging case, manage posterior capsular rupture, and realize a corneal stitch were rated 4.1, 3.2, 4.2, 2.4, respectively. We observed extensive variation in clinical exposure to CS and self-reported confidence to perform CS between European trainees. Females reported a mean of 18% fewer entire procedures than their male colleagues and were also less confident in their surgical skills (P < .05). Trainees in residency programs longer than 5 years performed fewer procedures and were less confident than trainees in residences of shorter duration (P < .001). The importance of fellowships to complete surgical education was rated 7.7 out of 10. CONCLUSIONS: CS training across European countries lacks harmony. Female ophthalmology trainees continue, as in other specialties, to experience apparent gender bias. European level recommendations seem necessary to raise and harmonize competency-based CS training programs and promote post-residency fellowship training programs.

Does methylphenidate treatment affect functional and structural ocular parameters in patients with attention deficit hyperactivity disorder? - A prospective, one year follow-up study.

Purpose: Methylphenidate hydrochloride, which blocks the reuptake mechanisms of dopamine and norepinephrine, is used in attention deficit hyperactivity disorder (ADHD) treatment. Methylphenidate has many general side effects including ocular findings. In this study, we investigated the long-term effects of methylphenidate treatment on functional and structural ocular parameters. Methods: In this prospective study, children with ADHD were evaluated. All patients underwent a detailed ophthalmic examination before methylphenidate treatment. All patients were examined in the 3rd, 6th, 9th, 12th months of methylphenidate treatment. Visual acuities, color vision, pupil diameters, static, dynamic and cycloplegic retinoscopy, intraocular pressure (IOP), anterior chamber depth (ACD), axial length (AL) were evaluated and recorded. Results: A total of 22 children were included in this study. The best-corrected visual acuities (BCVA) of all patients for both eyes were 0.0 logMAR, and 90.9% of patients had blue-purple color weakness before the treatment. After 1 year of treatment, none of the patients had any change in BCVA and color vision. However, an increase in myopic values of static retinoscopy and a decrease in hyperopic values of cycloplegic retinoscopy were found. Additionally, accommodation capacities were found to be decreased and AL was found to be increased significantly for both eyes. Pupil diameter, IOP, and ACD values did not change significantly. Conclusion: Our results suggest that patients with ADHD may have blue color vision deficiencies because of the decreased retinal dopamine levels. Additionally, structural and ocular parameters, especially accommodation capacity, may be affected by methylphenidate treatment.

Isolated abducens nerve palsy due to COVID-19.

Although coronavirus disease-2019 (COVID-19) is mainly a respiratory system disease, neurological complications due to peripheral and central nervous system involvement may be seen in these patients. In this case report, we described a patient with isolated abducens nerve palsy after COVID-19. The patient was a healthy 28-year-old man who developed isolated abducens nerve palsy 10 days after COVID-19. He had no systemic risk factors. He had 20 PD left esotropia (ET) at distance and 16 PD left ET at near in primary position and ET increasing to 25 PD in left gaze. He had left abduction deficiency. His cranio-orbital magnetic resonance imaging findings were normal. He was diagnosed as left isolated abducens nerve palsy and his findings were recovered after 2 months. COVID-19 may cause ocular motor nerve palsies. Although the pathological mechanism remains unclear, direct viral invasion, inflammatory and immune mechanisms may play role. Further case reports and studies are needed to support these findings.

Chickenpox Associated Retinitis and Occlusive Vasculitis in a Vaccinated Child: A Case Report and Literature Review.

Either retinitis and occlusive vasculitis are rare but vision threatening ocular complications of chickenpox in children. In this case report a 13-year-old girl who developed chickenpox 2 days before complaining with visual loss in her right eye is presented. She was vaccinated one dose of varicella zoster virus (VZV) vaccine when she was 12 months old. Best corrected visual acuity was counting fingers at 1.5 m in right eye. A subtle anterior segment inflammation and mild vitritis were observed. Fundoscopic examination of right eye showed ischemia in paracentral macula and white foci of retinitis along the superotemporal branch of retinal vessels. She was hospitalized and intravenous acyclovir treatment at 3 × 10 mg/kg daily dose was started. Serum IgM and IgG for VZV were positive. Aqueous humor PCR test was also reported positive for VZV DNA. Oral methylprednisolone was added at a dose of 64 mg/day at the 3rd day acyclovir treatment. Macular edema developed at 4th week of treatment and bevacizumab was administered intravitreally. After 3 injections retinal edema subsided completely. At 6-month follow-up retinal ischemia in superotemporal periphery was observed and photocoagulation was added to treatment.

A novel biomarker for increased intracranial pressure in idiopathic intracranial hypertension.

PURPOSE: Changes in optic disc and peripapillary structures associated with optic nerve edema in idiopathic intracranial hypertension (IIH), can be evaluated with spectral domain optical coherence tomography (SD-OCT). We aimed to evaluate the association between increased cerebrospinal fluid (CSF) opening pressure and changes in peripapillary structures detected by SD-OCT and to determine whether these changes can be used to assess the changes in CSF pressure without performing lumbar puncture (LP). STUDY DESIGN: Retrospective study METHODS: We included 54 eyes of 28 patients with bilateral papilledema who had peripapillary SD-OCT imaging within 24 h before the LP. Correlation between CSF pressure and peripapillary OCT parameters including maximal retinal thickness, maximal anterior retinal projection, maximal retinal nerve fiber layer (RNFL) thickness and Bruch membrane opening (BMO) was evaluated. RESULTS: Bruch Membrane opening and maximal RNFL thickness were significantly higher in patients with increased CSF pressure. There exist correlations between CSF pressure and BMO, maximal RNFL thickness and maximal retinal thickness. (Spearman's Rho: 0.791, 0.482 and 0.297, p < 0.001, < 0.001 and 0.029, respectively) The cut off value of BMO for the prediction of increased CSF pressure was 1785 µm, with a sensitivity of 78.8% and a specificity of 81%. The cut off value for maximal RNFL thickness was 174 µm, with a sensitivity of 75.8% and a specificity of 61.9%. CONCLUSION: Bruch membrane opening and maximal RNFL thickness can give an idea about increased CSF pressure values in IIH patients. Thus SD-OCT can be used to detect CSF pressure changes in these patients.

Vascular changes with optical coherence tomography angiography during aura of migraine: A case report.

PURPOSE: To demonstrate macular and optic disk vessel changes by optical coherence tomography angiography during and after a migraine attack with aura. METHODS: Case report. RESULTS: A 34-year-old healthy female patient was evaluated by optical coherence tomography angiography imaging during visual aura with phosphenes in the left visual field. Optical coherence tomography angiography imaging showed diffuse narrowing of the retinal vessels, decreased radial peripapillary capillary density, and decreased superficial and deep foveal vessel density in the right eye. These changes improved 3 hours after visual aura. The patient suffered from right eye pain and right-sided headache, which are typical for migraine, after the visual aura. CONCLUSION: These findings indicate that blood flow during migraine attack is reduced not only in the brain but also in the eye. Eye pain in migraine patients may be due to decreased blood flow in the eye. Restoring the vascular changes 3 hours after the visual aura suggests that vascular changes may be transient during a migraine attack.

Diplopia due to acquired Brown syndrome after COVID-19 infection.

Coronavirus disease 2019 (COVID-19) is a multisystem, inflammatory condition usually presenting with respiratory symptoms, such as fever, shortness of breath, and severe cough. It may also present with ocular, neurological, and musculoskeletal manifestations. However, since the emergence of the disease in 2019, only a few cases with ocular involvement have been reported in the literature. We present a case of acquired Brown syndrome secondary to COVID-19.