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We report a case of a 25-year-old woman with unilateral Coats’-like disease. Her brother was previously diagnosed with an autosomal dominant form of dyskeratosis congenita. Genetic testing was performed by screening the TERC gene for mutations and identified heterozygosity for the n.68_124del mutation. Our case demonstrates that the exudative retinopathy seen in Coats’-like disease can be caused by mutations in a telomere-capping gene TERC as a part of the dyskeratosis congenita spectrum without other systemic involvement. This is an interesting case that illustrates that retinal Coats’-like involvement can be the first manifestation of dyskeratosis congenita. [ABSTRACT FROM PUBLISHER]

The best known café-au-lait syndrome is neurofibromatosis type 1 (NF1). Legius syndrome (LS) is another, rarer syndrome with café-au-lait macules (CALMs). In young patients their clinical picture is often indistinguishable. We investigated the presence of choroidal abnormalities in syndromes with CALMs as a candidate tool for a more efficient diagnosis. Thirty-four patients with NF1 (14 with a truncating mutation, 14 with a non-truncating mutation and 6 with unknown mutation) and 11 patients with LS. All patients underwent an ophthalmological examination. Infrared images were performed. Choroidal nodules were diagnosed in 65% of the NF1 group. About 71% of NF1 patients with a truncating mutation and 50% of patients with a non-truncating mutation were found to have nodules. Choroidal nodules were seen in 18% of the LS patients, never more than one nodule/eye was detected in this group. Choroidal nodules are more abundantly present in NF1 genotypes with truncating mutations. In contrast, the number of choroidal nodules in LS is comparable with their presence in healthy individuals. Especially at an early age, when the clinical picture is incomplete, the detection of choroidal nodules is of diagnostic value, and helps in an appropriate genetic counselling and follow-up. These results support the suggestion to include choroidal nodules to the diagnostic criteria for NF1. [ABSTRACT FROM AUTHOR]

We present a newborn diagnosed with posterior amorphous corneal dystrophy (PACD). PACD is a rare disorder with partial or complete posterior lamellar corneal opacification. Genetic screening showed a deletion of chromosome 12q21.33-q22 containing the identified four small leucine-rich proteoglycans (SLRP’s) associated with this particular dystrophy. Neither parents were carrier of the deletion. To our knowledge, this is the first report of ade novomutation causing PACD. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to investigate the role of pattern reversal visual evoked potentials (pVEPs) in the screening and monitoring of optic pathway gliomas (OPGs) in children with and without neurofibromatosis type 1. Methods: A review of the English literature published between 1980 and 2012 was performed, with comparison of results of retro- and prospective studies. Results: Pattern reversal VEPs have a high sensitivity (85.7-100 %) for the diagnosis of OPGs, moreover they are safe and cost-effective. Conversely, they have a low specificity (43-83 %) and are not widely available. Besides, pattern reversal VEP results can be unreliable in young children, because of the need for a good cooperation. The studies that were analyzed have drawbacks, including the small sample size, the retrospective design, the differences in gold standard for diagnosis, the different interpretation of small changes in VEP results and the lack of control groups. Conclusion: There is still debate about the gold standard for the screening and follow-up of OPGs. The added value of pVEPs to the ophthalmic examination is controversial. Randomized controlled trials or prospective multicentre studies are necessary to assess with sufficient accuracy the sensitivity and specificity of pattern reversal VEPs in the screening for OPGs and its follow-up. [ABSTRACT FROM AUTHOR]

Unlabelled: Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease affecting the premature infant with an incompletely vascularized retina. The spectrum of ophthalmological findings in ROP exists from minimal sequelae, which do not affect vision, to bilateral retinal detachment and total blindness. With the increased survival of very small infants, retinopathy of prematurity has become one of the leading causes of childhood blindness. Over the past two decades, major advances have been made in understanding the pathogenesis of ROP, to a large extent as a result of changes in clinical risk factors (oxygen and non-oxygen related) and characteristics observed in ROP cases. This article provides a literature review on the evolution in clinical characteristics, classification and treatment modalities and indications of ROP. Special attention is hereby paid to the neonatal factors influencing the development of ROP and to the necessity for everyone caring for premature babies to have a well-defined screening and treatment protocol for ROP. Such screening protocol needs to be based on a unit-specific ROP risk profile and, consequently, may vary between different European regions.Conclusion: Retinopathy of prematurity is an important cause of ocular morbidity and blindness in children. With better understanding of the pathogenesis, screening and treatment guidelines have changed over time and are unit specific. [ABSTRACT FROM AUTHOR]

Purpose: In 15 patients with idiopathic uveitis associated with retinal vasculitis, HLA DRB1 gene testing was performed to detect a possible association. 11 patients tested positive and 4 negative for the HLA DRB1 × 15 allele. The presence of the HLA DRB1 × 15 haplotype might be associated with a higher susceptibility to develop Multiple Sclerosis (MS)., Methods: In this case series, we describe the ophthalmological and neurological findings in 10 HLA DR15-positive patients and 4 HLA DR15-negative patients that had neurological workup, including Magnetic Resonance Imaging (MRI) of the brain., Results: All patients had granulomatous ocular inflammation with either panuveitis or intermediate uveitis. MRI of the brain showed white matter lesions in 13 patients (9/10 and 4/4 respectively) of which 4 patients were eventually diagnosed with MS (3/10 and 1/4 respectively)., Conclusion: Although the majority of tested patients was carrying at least one HLA DRB1-15 allele, there was no difference in ophthalmological and neurological findings in both groups.

Purpose: To assess the validity of the GoCheck Kids photoscreening application (Gobiquity Mobile Health, Scottdale, AZ) on iPhone, which was used (2018-2022) as standard of care by Child and Family (Kind en Gezin) to detect amblyopia risk factors in children 12-30 months of age., Methods: Between August 2021 and May 2022, 453 children 11-16 months of age underwent a confirmatory ophthalmic examination within 2 months of GoCheck Kids photoscreening at Child and Family, Flanders, Belgium. Additionally, manual review was performed by specialists of GoCheck Kids. Diagnostic metrics were assessed using the 2013 criteria of the American Association for Pediatric Ophthalmology and Strabismus as reference., Results: Specificity was similar for automatic screening with or without manual review: 90.0% (95% CI, 87.6%-92.3%) and 90.3% (95% CI, 88.0%-92.7%), respectively. Sensitivity was estimated at 52.0% (95% CI, 35.6%-68.4%) for automatic grading and 56.0% (95% CI, 39.7%-72.3%) after manual review. Positive predictive values for automatic screening and manual review were, respectively, 23.2% (95% CI, 13.9-32.5) and 25.5% (95% CI, 15.8-35.1). Negative predictive values for automatic screening and manual review were, respectively, 97.0% (95% CI, 95.6-98.4) and 97.2 (95% CI, 95.8-98.6)., Conclusions: In our study cohort of children around 12 months of age, the GoCheck Kids application had a specificity of 90% for the targeted amblyopia risk factors, with sensitivity just over 50%., (Copyright © 2024 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Mutations in the N-terminal WD40 domain of coatomer protein complex subunit α (COPA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis, and nephritis. We described 3 heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.R1058C, and p.R1142X) in 6 children from 3 unrelated families with a similar syndrome of autoinflammation and autoimmunity. We showed that these CTD COPA mutations disrupt the integrity and the function of coat protein complex I (COPI). In COPAR1142X and COPAR1058C fibroblasts, we demonstrated that COPI dysfunction causes both an anterograde ER-to-Golgi and a retrograde Golgi-to-ER trafficking defect. The disturbed intracellular trafficking resulted in a cGAS/STING-dependent upregulation of the type I IFN signaling in patients and patient-derived cell lines, albeit through a distinct molecular mechanism in comparison with mutations in the WD40 domain of COPA. We showed that CTD COPA mutations induce an activation of ER stress and NF-κB signaling in patient-derived primary cell lines. These results demonstrate the importance of the integrity of the CTD of COPA for COPI function and homeostatic intracellular trafficking, essential to ER homeostasis. CTD COPA mutations result in disease by increased ER stress, disturbed intracellular transport, and increased proinflammatory signaling.

Introduction: Anterior segment ischemia (ASI) is a rare but potentially sight-threatening complication of strabismus surgery. Preoperative imaging of the iris vasculature may be appropriate in patients at high risk of ASI. In clinical practice, this is currently done through invasive fluoresceine or indocyanine green (ICG) angiography and in study context through laser speckle contrast imaging. The purpose of this study is to investigate the use of noninvasive optical coherence tomography angiography (OCTA) as a screening tool for ASI in strabismus surgery., Methods: A prospective interventional trial was conducted from September until November 2021 at the Leuven University Hospitals. Patients scheduled for strabismus surgery to one or more rectus muscles underwent OCTA preoperatively and at day two postoperatively. The vascular density was calculated for all images with sufficient quality. Information on risk factors for ASI was collected. A two-sided t-test was used for pairwise comparison pre- and postoperatively. Filling defects were qualitatively assessed., Results: Eighteen patients were included. In only seven muscles of five patients, images of sufficient quality on both image acquisition moments were suitable for statistical analysis. The mean age of these patients was 45.2 years and 40% were women. A mean vascular density of 53,099% preoperatively and a mean density of 50,782% postoperatively with a mean decrease of 2.316% ( p  = .318, 95% confidence interval [-2.886; 7.516]) was found. No filling defects were identified., Discussion: The small final number of images contributing to statistical analysis shows that current application of the OCTA technique is hampered by poor image quality and poor repeatability. We identified difficulties in the image acquisition process and variable pupil size due to iris muscle contractions as the two main reasons. We believe that adjustments in the OCTA software such as pupil tracking and tracking of iris vasculature can largely overcome these limitations. Furthermore, there is a need for a normative database to allow good quantitative comparison and risk stratification. We conclude that OCTA could be suitable for screening in prevention of ASI with both qualitative and quantitative analysis if adjustments are made.

Since multiple sclerosis (MS) is characterized by an unpredictable disease course, accurate prognosis and personalized treatment constitute an important challenge in clinical practice. We performed a qualitative systematic review to assess the predictive value of retinal layer measurement by spectral-domain optical coherence tomography (SD-OCT) in MS patients. Longitudinal MS cohort studies that determined the risk of clinical deterioration based on peripapillary retinal nerve fiber layer (pRNFL) and/or macular ganglion cell-inner plexiform layer (mGCIPL) atrophy were included. Our search strategy and selection process yielded eight articles in total. Of those, five studies only focused on patients with a relapsing-remitting disease pattern (RRMS). After correction for confounders such as disease duration, we found that (1) cross-sectional measurement of pRNFL thickness ≤ 88 µm; (2) cross-sectional measurement of mGCIPL thickness < 77 µm; (3) longitudinal measurement of pRNFL thinning > 1.5 µm/year; and (4) longitudinal measurement of mGCIPL thinning ≥ 1.0 µm/year is associated with an increased risk for disability progression in subsequent years. Longitudinal mGCIPL assessment consistently resulted in the highest risk estimates in our analysis. Within these studies, inclusion and exclusion criteria accounted for the retinal degeneration inherent to (acute) optic neuritis (ON). This small systematic review provides additional evidence that OCT-measured pRNFL and/or mGCIPL atrophy can predict disability progression in RRMS patients. We therefore recommend close clinical follow-up or initiation/change of treatment in RRMS patients with increased risk for clinical deterioration based on retinal layer thresholds, in particular when other poor prognostic signs co-occur., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

We investigated a possible association between the acute onset of esotropia and tablet or smartphone use in children. We characterized the clinical aspects of esotropia associated with tablet or smartphone use. The medical records of 10 children aged between 5 and 15 years old with presumably tablet or smartphone associated esotropia were reviewed regarding orthoptic examination and cycloplegic refraction. Legal guardians of the children were asked to fill in a questionnaire regarding tablet and smartphone use of their child. This questionnaire was also conducted in a control group of age-matched children. The results of this questionnaire were compared to search for possible determinants of tablet or smartphone associated esotropia. All 10 patients presented with a comitant esotropia ranging from 8 to 45 prism diopters with no significant difference between near and far. The mean age of onset was 9.8 years. Cycloplegic refraction showed a mild hyperopia in eight patients, a mild myopia in one patient and emmetropia in the other patient. All patients had near full refractive correction at the onset of esotropia. Diplopia was reduced after visual hygiene recommendations, however in six patients, strabismus surgery was needed. The working distance was significantly shorter in the 10 cases compared to the controls. In children with acute acquired esotropia, we found a statistically significant association with a smaller working distance during tablet or smartphone use compared to age-matched controls. We hypothesize that intensive near viewing can be a precipitating factor in this type of esotropia.

We describe a four-year-old girl with bilateral severe iris hypoplasia and secondary ocular hypertension. Genetic testing revealed a de novo deletion in the FOXC1 gene, establishing the diagnosis of Axenfeld-Rieger syndrome (ARS). The girl developed a gradually increasing exotropia, up to 95 prism diopters by the age of 3 years wherefore strabismus surgery was performed. Intra-operatively, only very rudimentary developed medial and lateral rectus muscles were found. This is the first observation of pronounced hypoplasia of both medial and lateral rectus muscles associated with ARS.

Purpose: This paper is a scoping review of research on multiple sclerosis (MS)-associated uveitis to determine its epidemiology, pathophysiology, clinical features and treatment., Methods: A comprehensive search of the medical databases MEDLINE (PubMed), EMBASE, Web of Science and Cochrane was carried out on 25 November 2019, to identify papers published between 1980 and 2019 that focus on patients with MS-associated uveitis., Results: Based on large cohort studies (n ≥ 1000), the prevalence of uveitis in patients with MS is estimated to be 0.53-1.34% (mean = 0.83%), and MS is diagnosed in 0.52-3.20% (mean = 1.30%) of patients with uveitis. The condition is most frequent among middle-aged women. Patients usually complain of floaters and/or blurred vision, with bilateral intermediate uveitis (with retinal vasculitis) as the most frequent ophthalmological finding. Both MS and intermediate uveitis are associated with HLA-DRB1*15:01 and IL-2RA gene polymorphism rs2104286 A > G, suggesting a common genetic background. T cells, and possibly B cells, play an important role in both autoimmune disorders. Multiple sclerosis (MS)-related uveitis is classically treated as non-infectious uveitis, with corticosteroids as the first treatment step. Other treatments include immunosuppressants, cryotherapy, laser photocoagulation and vitrectomy. These treatment options have a limited, if any, effect on the course of MS and can be complicated by side-effects. As treatment strategies for MS have increased in the last decade, it would be interesting to evaluate the efficacy of these new treatments during the course of uveitis. Moreover, the correlation between retinal periphlebitis and MS could be established more accurately with the recently developed techniques of wide-field fluorescein angiography in a large cohort of MS patients., Conclusion: MS-associated uveitis is a rare, highly discussed pathology about which much is still unknown. Large epidemiological studies and extrapolation of new MS treatments to this condition are warranted., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Deficiency of human adenosine deaminase 2 (DADA2) is an auto-inflammatory inborn error of immunity caused by biallelic deleterious mutations in the gene encoding ADA2. The purpose of this article is to raise awareness among ophthalmologists and pediatricians to consider DADA2 as a possible diagnosis for patients with acute onset of diplopia. The authors describe two pediatric patients who presented with double vision due to uni-lateral adduction deficit, and discuss the importance of recognizing this clinically as an ophthalmologist. If a child presents with a sudden eye movement abnormality, ophthalmologists must be aware of the possibility of an ischemic insult due to an underlying genetic disorder (eg, DADA2), especially in patients with a positive familial history or associated clinical signs such as a personal history of characteristic skin lesions or paresis of other cranial nerves. Given the multi-organ involvement in this disorder, a multi-disciplinary approach is crucial to have a timely diagnosis and to treat this rare disorder appropriately. [ J Pediatr Ophthalmol Strabismus . 2021;58(4):e22-e26.] .

Competing Interests: The authors declare no conflicts of interest.

Introduction: Treatment of the anterior segment problems in cystinosis is challenging as oral cysteamine is ineffective in the treatment of corneal problems because of its avascular structure. Although cysteamine eye drops have been formulated to counter this issue, the stability of cysteamine in these off-licensed formulations and treatment compliance are major problems. The aim of this retrospective study was to determine the efficacy of a compounded preparation of aqueous 0.5% cysteamine eye drops in the management of corneal complications of cystinosis., Methods: Data of patients attending the multidisciplinary cystinosis clinic at the University Hospitals Leuven, Belgium between January 2015 and December 2018 were analyzed. All cystinosis patients were treated with the compounded preparation of aqueous 0.5% cysteamine eye drops and oral cysteamine., Results: A total of 12 patients were treated with the compounded preparation of aqueous 0.5% cysteamine eye drops, of whom 75% were aged > 18 years (n = 9). The mean instillation frequency of the cysteamine eye drops was 3.3 drops/eye per day, and the mean number of hospital visits was two per year. All patients showed photophobia, > 30% corneal infiltration, blepharospasm, eye pain and conjunctival hyperemia during the study period. None of these symptoms improved with treatment with aqueous compounded 0.5% cysteamine eye drops. The corneal cystine crystal score was ≥ 2 in all patients at the last  visit., Conclusion: Treatment with the compounded preparation of aqueous 0.5% cysteamine eye drops, combined with oral cysteamine, was not effective in reducing corneal cystine crystal deposition and other ocular symptoms in these patients with cystinosis., Funding: Recordati Rare Diseases.

Ocular neuromyotonia (ONM) is a rare eye movement disorder, presenting as a paroxysmal involuntary spasm of one or more extra-ocular muscles, that can persist for a few seconds up to several minutes. The phenomenon is caused by the contraction of an extra-ocular muscle, excited by a damaged nerve, which leads to delayed muscle relaxation. We present eight patients with this rare condition together with an overview of the literature on all published ONM cases. One of the presented cases is possibly secondary to hypovitaminosis D. This association has not been reported previously in the literature. A possible underlying mechanism is given.

Background: Paraneoplastic melanocytic proliferation (bilateral diffuse uveal melanocytic proliferation, BDUMP) is a rare but devastating disease that causes progressive visual loss in patients who usually have an occult malignancy. Visual loss occurs as a result of paraneoplastic changes in the uveal tissue., Methods: In a masked fashion, the serum of two patients with BDUMP was evaluated for the presence of cultured melanocyte elongation and proliferation (CMEP) factor using cultured human melanocytes. We evaluated the efficacy of plasmapheresis as a treatment modality early in the disease in conjunction with radiation and chemotherapy., Results: The serum of the first case patient was investigated after plasmapheresis and did not demonstrate proliferation of cultured human melanocytes. The serum of the second case was evaluated prior to treatment with plasmapheresis and did induce this proliferation. These findings are in accordance with the diminution of CMEP factor after plasmapheresis. Treatment with plasmapheresis managed to stabilise the ocular disease progression in both patients., Conclusions: In the past, visual loss due to paraneoplastic melanocytic proliferation was considered progressive and irreversible. We treated two patients successfully with plasmapheresis and demonstrated a relation between CMEP factor in the serum of these patients and proliferation of cultured melanocytes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: To characterize the choroidal thickness of the papillomacular region in young healthy individuals using spectral-domain optical coherence tomography (SD-OCT)., Methods: Papillary and macular SD-OCT scans were obtained using an enhanced depth imaging mode. Digital retinography was used to assess any overlapping areas and to determine the papillomacular region. Spearman's correlations were used to explore the relationship between the different regional choroidal thicknesses., Results: Sixty-three volunteers aged 21.6 ± 1.1 years were included. There was a significant asymmetry in choroidal thickness throughout the 10-mm length model (p < 0.001). While the choroid was shown to thicken as the distance from the optic disc increased (p < 0.001), each of the 500-µm blocks of the papillomacular region were significantly thinner than their nasal counterparts (p < 0.02 in all pairwise comparisons)., Conclusion: In young healthy individuals, the choroid under the papillomacular region appears to be thinner than in other areas. These differences could relate to specificities of the retina overlying this region., (© 2014 S. Karger AG, Basel.)

Unlabelled: Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder, caused by mutations in the NF1 gene, located on chromosome band 17q11.2. In 1988, the National Institutes of Health created specific criteria for the diagnosis of NF1. Four cardinal criteria are assessed through ophthalmological screening: Lisch nodules, optic pathway glioma, a distinctive osseous lesion (sphenoid dysplasia), and the (orbital) plexiform neurofibroma. NF1 patients are prone to the development of central and peripheral nervous system tumors. Especially young children are at risk for growing optic pathway gliomas that can threaten their sight. From an early age, children with NF1 undergo regular ophthalmological examinations. Little is known about the natural progress of these clinical features and the guidelines for screening and follow-up are controversial. Several questions remain unanswered., Conclusion: Most of these questions could be solved by better understanding of the natural history of optic pathway gliomas. There is a tendency towards using vision as a primary objective in clinical treatment trials; this way we can evaluate new treatment strategies and focus specifically on visual evolution so we will be able to select even more carefully which patient would benefit treatment. For future clinical trials, a standardized visual acuity assessment protocol is therefore mandatory.

Enhanced S-cone syndrome is a rare, slowly progressive autosomal recessively inherited retinal degeneration related to mutations in the NR2E3 gene. Patients often present with night blindness, visual loss and visual field abnormalities. Patients with enhanced S-cone syndrome exhibit a variable clinical phenotype associated with various degrees of pigmentary changes and foveal schisis. We report a 14-month-old boy with an unusual funduscopic appearance. The diagnosis of enhanced S-cone syndrome was suggested by the uniquely abnormal electroretinographic pattern and was confirmed by the finding of homozygous NR2E3 mutations.

Cytomegalovirus (CMV) is the leading cause of known congenital viral infections. Approximately 90% of congenitally infected newborns exhibit no clinical abnormalities at birth. In 5% to 15%, a wide spectrum of clinical signs is present at birth. Ophthalmological signs are seen in a large percentage of symptomatic patients but rarely in otherwise asymptomatic infants. Chorioretinitis, optic atrophy, and cortical visual impairment are the most frequent causes of visual problems in congenitally infected infants. There is no clear consensus in the literature on screening or treatment modalities concerning the ophthalmological aspects of congenital CMV. Further prospective studies are needed to set up guidelines for ophthalmological screening and treatment of infants with congenital CMV., (Copyright 2012, SLACK Incorporated.)