Ocular Defects Research Articles

Nystagmus in Children - a Survey

Nystagmus describes an involuntary, periodic movement of one or both eyes. About 1/600 children and adolescents have nystagmus, most of them idiopathic infantile nystagmus (IIN), also called "congenital nystagmus", which can be caused by mutations in the FRMD7 gene. Other frequent forms of nystagmus are latent nystagmus, which is usually associated with infantile strabismus, and nystagmus associated with albinism. Sometimes difficult to distinguish in young infants is a sensory nystagmus, where a defect in the visual system reduces vision and causes nystagmus. Causes include retinal dystrophies, congenital stationary night blindness and structural ocular defects including optic nerve hypoplasia or dense bilateral congenital cataracts. Unilateral nystagmus can be the sign of an anterior visual pathway lesion. Seesaw nystagmus may be associated with suprasellar and mesodiencephalic lesions and - rarely - with retinal dystrophies.The ophthalmology plays a key role in identifying the form of nystagmus. Children with new onset nystagmus, with spasmus nutans, with vertical or unilateral nystagmus and those with seesaw nystagmus require neurologic evaluation including imaging of the brain.The treatment of nystagmus depends on the underlying cause. Even minor refractive errors should be corrected, contact lenses offer advantages over glasses.Gabapentin and memantine, possibly also carbonic anhydrase inhibitors, are effective in treating IIN, nystagmus in albinism and sensory nystagmus. Nevertheless, pharmacologic treatment of nystagmus is rarely used in children; the reasons are the limited effects on vision, the need for lifelong therapy, and potential side effects. Eye muscle surgery (Anderson procedure, Kestenbaum procedure) can correct a nystagmus-related anomalous head posture. The concept of "artifical divergence" of Cüppers may help to decrease nystagmus intensity in patients whose nystagmus dampens with convergence. The four-muscle-tenotomy, which involves disinsertion and reinsertion of the horizontal muscles at the original insertion of both eyes, has a proven but limited positive effect on visual acuity.

Prosthetic approach following traumatic evisceration: a case report

A 20-year-old male patient was referred to Prosthodontic Department, Dental Hospital of Hasanuddin University, Makassar with chief complaint of disfiguration of the face. Medical history revealed a significant trauma to the left eye 6 months prior which stayed after evisceration. Patient has never used prosthetic eye afterwards. Examination of the left eye socket revealed a healthy conjunctiva covering the posterior wall of the anophthalmic socket with syn-chronous motions and absence of infection or inflammation signs. Sulcus depth was sufficient enough to retain prosthetic eye. This article presents rehabilitation of the ocular defect with customized acrylic-based ocular prosthe-sis to increase patient’s appearance and to prevent further shrinkage of the eye socket. Preliminary impression was done using customized tray fabricated from modelling wax and hydrocolloid irreversible impression material. An in-traocular custom tray for secondary impression was fabricated with acrylic resin and modified with a syringe that at-tached to the custom tray. Secondary impression of the defect was recorded using polyvinyl siloxane light viscosi-ty material followed by wax pattern fabrication using modelling wax. The wax pattern was tried in patient’s socket and checked for size, comfort, support, fullness, and then packed with tooth colored heat cure acrylic resin. After deter-mining the location and diameter of the iris with an optical vernier pupillary distance ruler, the color of sclera was de-termined by shade guide and confirmed with technician using digital photo. Ocular prosthesis was fabricated after-wards and inserted into the eye socket and evaluated for suitability, aesthetic and also movements with the contra-lateral eye. It is concluded that customized ocular prosthesis was significantly more aesthetic than pre-fabricated one with better contouring, color matching, and coordinated movements with the contralateral eye. This prosthetic ap-proach may restore patient’s appearance, increase their self-esteem, and improve their quality of life.

Heterozygous mutations in SOX2 may cause idiopathic hypogonadotropic hypogonadism via dominant-negative mechanisms.

Pathogenic SRY-box transcription factor 2 (SOX2) variants typically cause severe ocular defects within a SOX2 disorder spectrum that includes hypogonadotropic hypogonadism. We examined exome-sequencing data from a large, well-phenotyped cohort of patients with idiopathic hypogonadotropic hypogonadism (IHH) for pathogenic SOX2 variants to investigate the underlying pathogenic SOX2 spectrum and its associated phenotypes. We identified 8 IHH individuals harboring heterozygous pathogenic SOX2 variants with variable ocular phenotypes. These variant proteins were tested in vitro to determine whether a causal relationship between IHH and SOX2 exists. We found that Sox2 was highly expressed in the hypothalamus of adult mice and colocalized with kisspeptin 1 (KISS1) expression in the anteroventral periventricular nucleus of adult female mice. In vitro, shRNA suppression of mouse SOX2 protein in Kiss-expressing cell lines increased the levels of human kisspeptin luciferase (hKiss-luc) transcription, while SOX2 overexpression repressed hKiss-luc transcription. Further, 4 of the identified SOX2 variants prevented this SOX2-mediated repression of hKiss-luc. Together, these data suggest that pathogenic SOX2 variants contribute to both anosmic and normosmic forms of IHH, attesting to hypothalamic defects in the SOX2 disorder spectrum. Our study describes potentially novel mechanisms contributing to SOX2-related disease and highlights the necessity of SOX2 screening in IHH genetic evaluation irrespective of associated ocular defects.

Zika virus induced microcephaly and aberrant hematopoietic cell differentiation modeled in novel neonatal humanized mice.

Immunocompetent and immunocompromised murine models have been instrumental in answering important questions regarding ZIKV pathogenesis and vertical transmission. However, mimicking human congenital zika syndrome (CZS) characteristics in these murine models has been less than optimal and does not address the potential viral effects on the human immune system. Here, we utilized neonatal humanized Rag2-/-γc-/- mice to model CZS and evaluate the potential viral effects on the differentiation of human hematopoietic stem cells in vivo. Newborn Rag2-/-γc-/- mice were engrafted with ZIKV-infected hematopoietic stem cells (HSC) and monitored for symptoms and lesions. Within 13 days, mice displayed outward clinical symptoms that encompassed stunted growth, hunched posture, ruffled fur, and ocular defects. Striking gross pathologies in the brain and visceral organs were noted. Our results also confirmed that ZIKV actively infected human CD34+ hematopoietic stem cells and restricted the development of terminally differentiated B cells. Histologically, there was multifocal mineralization in several different regions of the brain together with ZIKV antigen co-localization. Diffuse necrosis of pyramidal neurons was seen with collapse of the hippocampal formation. Overall, this model recapitulated ZIKV microcephaly and CZS together with viral adverse effects on the human immune cell ontogeny thus providing a unique in vivo model to assess the efficacy of novel therapeutics and immune interventions.

Genome-wide screening reveals the genetic basis of mammalian embryonic eye development

BackgroundMicrophthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways required for early eye development through systematic forward screening of the mammalian genome.ResultsQuery of the International Mouse Phenotyping Consortium (IMPC) database (data release 17.0, August 01, 2022) identified 74 unique knockout lines (genes) with genetically associated eye defects in mouse embryos. The vast majority of eye abnormalities were small or absent eyes, findings most relevant to MAC spectrum disease in humans. A literature search showed that 27 of the 74 lines had previously published knockout mouse models, of which only 15 had ocular defects identified in the original publications. These 12 previously published gene knockouts with no reported ocular abnormalities and the 47 unpublished knockouts with ocular abnormalities identified by the IMPC represent 59 genes not previously associated with early eye development in mice. Of these 59, we identified 19 genes with a reported human eye phenotype. Overall, mining of the IMPC data yielded 40 previously unimplicated genes linked to mammalian eye development. Bioinformatic analysis showed that several of the IMPC genes colocalized to several protein anabolic and pluripotency pathways in early eye development. Of note, our analysis suggests that the serine-glycine pathway producing glycine, a mitochondrial one-carbon donator to folate one-carbon metabolism (FOCM), is essential for eye formation.ConclusionsUsing genome-wide phenotype screening of single-gene knockout mouse lines, STRING analysis, and bioinformatic methods, this study identified genes heretofore unassociated with MAC phenotypes providing models to research novel molecular and cellular mechanisms involved in eye development. These findings have the potential to hasten the diagnosis and treatment of this congenital blinding disease.

Innovative Therapeutic Approaches for the Treatment of the Ocular Morbidities in Patients with EEC Syndrome.

Ectrodactyly-Ectodermal dysplasia-Clefting (EEC) syndrome is caused by heterozygous missense point mutations in the p63 gene, an important transcription factor during embryogenesis and for stem cell differentiation in stratified epithelia. Most of the cases are sporadic, related to de novo mutations arising during early-stage development. Familial cases show an autosomic dominant inheritance. The major cause of visual morbidity is limbal stem cell failure, which develops in the second to third decade of life. Patients often show ocular surface alterations, such as recurrent blepharitis and conjunctivitis, superficial microlesions of the cornea, and spontaneous corneal perforation and ulceration, leading to progressive corneal clouding and eventually visual loss. No definitive cures are currently available, and treatments to alleviate symptoms are only palliative. In this review, we will discuss the proposed therapeutic strategies that have been tested or are under development for the management of the ocular defects in patients affected by EEC syndrome: (i) gene therapy-based approaches by means of Allele-Specific (AS) siRNAs to correct the p63 mutations; (ii) cell therapy-based approaches to replenish the pool of limbal stem cells; and (iii) drug therapy to correct/bypass the genetic defect. However, as the number of patients with EEC syndrome is too limited, further studies are still necessary to prove the effectiveness (and safety) of these innovative therapeutic approaches to counteract the premature differentiation of limbal stem cells.

An alternative technique by using digital photography and UV printing for fabricating a custom made ocular prosthesis.

A person becomes disabled when they lose any of their sensory organs, the eye being one of the most delicate. Loss of an eye can happen due to different reasons and can be restored using different materials and strategies. Ocular defects and congenital deformations show up as a result of tumors or injury. For the most part, fabricated eyes are accessible as ocular prostheses. This method describes how to create a custom ocular prosthesis using a digital photo and UV printing. The greatest esthetically pleasing results are also achieved using this production method, which does not necessitate painting or color-selecting expertise. Both psychologically and esthetically, the patient was satisfied.

Characteristics of Ocular Inflammatory Side Effects Associated with Immune Checkpoint Inhibitors in a Northern California Population

ABSTRACT Purpose To characterize the ocular inflammatory side effects associated with immune checkpoint inhibitor (CPI) treatment in a Northern California population. Design Retrospective case series. Participants Patients receiving CPI within an integrated healthcare delivery system. Methods All patients within Kaiser Permanente Northern California receiving CPI between January 1, 2012 and November 1, 2018 were identified. Medical records of those seen in the ophthalmology clinic at least once were retrospectively reviewed. Main Outcome Measures Type and duration of ocular inflammation, indication for and exposure to CPI, time from exposure to diagnosis of ocular inflammation. Results 31 cases of ocular inflammation were identified in 5061 patients (0.61%) receiving CPI. Mean ± SD age was 67 ± 11.9 (range 38–89). Mean time from exposure to diagnosis was 6.8 ± 5.5 months (range 0.5–17). 87% of cases were bilateral, and 43% of cases were chronic. Average ophthalmology follow-up was 16 ± 18 months (range 0–71). 16/31 (52%) had anterior uveitis, 7/31 (23%) had serous retinal detachment or panuveitis resembling Vogt-Koyanagi-Harada syndrome, 4/31 (13%) had papillitis, and 6/31 (19%) had diplopia or ocular motility defect. There was one case each (3.2%) of melanoma associated retinopathy, corneal edema, granulomatous lacrimal gland enlargement, and choroidal neovascularization. Conclusions Ocular inflammation is a rare immune associated side effect of CPI treatment, the most common manifestation of which is anterior uveitis.

Identification of HSPA8 as an interacting partner of MAB21L2 and an important factor in eye development.

Pathogenic variants in human MAB21L2 result in microphthalmia, anophthalmia, and coloboma. The exact molecular function of MAB21L2 is currently unknown. We conducted a series of yeast two-hybrid (Y2H) experiments to determine protein interactomes of normal human and zebrafish MAB21L2/mab21l2 as well as human disease-associated variant MAB21L2-p.(Arg51Gly) using human adult retina and zebrafish embryo libraries. These screens identified klhl31, tnpo1, TNPO2/tnpo2, KLC2/klc2, and SPTBN1/sptbn1 as co-factors of MAB21L2/mab21l2. Several factors, including hspa8 and hspa5, were found to interact with MAB21L2-p.Arg51Gly but not wild-type MAB21L2/mab21l2 in Y2H screens. Further analyses via 1-by-1 Y2H assays, co-immunoprecipitation, and mass spectrometry revealed that both normal and variant MAB21L2 interact with HSPA5 and HSPA8. In situ hybridization detected co-expression of hspa5 and hspa8 with mab21l2 during eye development in zebrafish. Examination of zebrafish mutant hspa8hi138Tg identified reduced hspa8 expression associated with severe ocular developmental defects, including small eye, coloboma, and anterior segment dysgenesis. To investigate the effects of hspa8 deficiency on the mab21l2Arg51_Phe52del allele, corresponding zebrafish double mutants were generated and found to be more severely affected than single mutant lines. This study identifies heat shock proteins as interacting partners of MAB21L2/mab21l2 and suggests a role for this interaction in vertebrate eye development.

Advances and prospects of platelet-rich plasma therapy in veterinary ophthalmology.

In the recent decades, there has been a significant uptick on the use of platelet-rich plasma (PRP) as a better alternative for ophthalmologic therapies in pathologies, primarily of the ocular surface. PRP is a class of liquid platelet concentrate containing a supra-physiological concentration of platelets in a relatively small amount of plasma. Its potential to heal various tissues has piqued interest in its therapeutic application as a biomaterial in regenerative medicine. It is currently a popular therapeutic agent in plastic surgery, cardiothoracic surgery, reconstructive surgery, and even oral and maxillofacial surgery. Based on the data from in vitro and in vivo studies, it can be concluded that PRP possesses adequate therapeutic potential in ocular pathologies, especially those involving cornea. In addition, the high concentrations of growth factors (TGF-β, VEGF, EGF) present in the PRP accelerate the healing of the corneal epithelium. PRP has great therapeutic prospects in veterinary ophthalmology as a regenerative therapeutic modality. However, several variables are yet to be defined and standardized that can directly affect the efficacy of PRP application in different ophthalmic conditions. There is a shortage of research on the use of PRP in ocular surface defects compared to the number of studies and reports on the use of autologous and allogeneic serum eye drops. Therefore, a data-driven approach is required to generate consensus/guidelines for the preparation, characterization, and therapeutic use of PRP in veterinary ophthalmology. This review aims to inform readers of the latest research on PRP, including its preparation methods, physiological and biochemical properties, clinical applications in veterinary ophthalmology, and their safety and efficacy.

Symbiosis of Conventional Modality and Digital Imaging Technique for Rehabilitating an Ocular Defect

Anophthalmia leads to both physical and social disability which affects the quality and day-to-day functioning of an individual. This article tends to describe the rehabilitation of unilateral anophthalmia by a custom-made eye prosthesis. Stock-made eye prosthesis once served as a boon to prosthodontists, but with the recent advances in the field of technology, custom-made eye prosthesis is preferred more as they cater the demand of the patient in a more socially acceptable manner. Iris positioning has been a major challenge to the prosthodontists since beginning, but with the advent of modern-day technology, things have been made easier and repeatable with commendable accuracy. This article describes a symbiosis of both conventional and digital imaging modality in rehabilitating the left ocular area just by superimposition and comparison of soft- and hard-tissue landmarks manually and digitally.

Ocular surface health affects the quality of life of the elderly

AbstractPurpose: To examine the association of ocular surface health with the quality of life (QoL) in a population‐based cohort of older people.Methods: This cross‐sectional study included 601 subjects born between years 1933–1956 and living in Savitaipale, Finland. Various ocular surface health parameters were evaluated, including Schirmer's I test, non‐invasive tear break‐up time (NIBUT), corneal and conjunctival staining, conjunctival redness, blepharitis, Meibomian gland dysfunction (MGD), and Ocular Surface Disease Index (OSDI). For QoL measurements 15D, Medical Outcomes Study 36‐Item Short Form Health Survey (MOS SF‐36), and Beck's Depression Inventory.(BDI‐II) were used. Multiple linear regression was used to examine the effects of ocular surface health on QoL.Results: OSDI scores affected majority of the MOS SF‐36 scales as well as 15D and BDI‐II scores (p < 0.05). BDI score worsened with increasing corneal and conjunctival staining and MGD scores (p = 0.004, p = 0.001, and p = 0.03, respectively). Physical and emotional health‐associated role limitations increased with increased conjunctival redness (p = 0.007 and p = 0.005, respectively). In addition, emotional well‐being was affected by conjunctival redness, blepharitis, MGD, and NIBUT (p < 0.05).Conclusions: The symptoms experienced by the participants affect various aspects of well‐being according to our results. Of the ocular surface signs, the ocular surface tissue defects appear to play more significant role in worsening of the general health‐related QoL, whereas the aqueous deficiencies alone do not. The health of ocular surface is an important factor of the QoL and merits to be taken account in clinical assessment of people and these symptoms should be treated accordingly.

Amniotic membrane as a substrate and delivery vehicle for stem cells

AbstractNew therapeutic concepts and clinical strategies are emerging for the different kinds of human amniotic membranes (hAM). There are new commercial forms of hAM that are under investigation for old and new applications, from ocular surface epithelial persistent defects to the hAM extract eyedrops or the new use of hAM as a delivery platform and substrate for stem cells for ocular surface repair.Although there are more substrates used as support for growth, maintenance, and delivery of cultivated stem cells onto the ocular surface, hAM is still the most used universally, followed by fibrin‐based substrates. This is due to the notable biological properties of this live tissue. The only disadvantage may be that it must come from tissue banks and as such, there can be some shortages and the cost is not irrelevant.Several other types of synthetic substrates such as lotrafilcon A, siloxane hydrogels or poly lactide‐co‐glycolic acid (PLGA) polymers, have been used over the last years to facilitate cell culture and the subsequent transplantation onto the ocular surface. In addition, several polymeric biomaterials like polycaprolactone, polylactic glycolic acid, chitosan and gelatin membranes, collagen or elastin‐like polymers are being also used to support ocular epithelial cells in preclinical studies. However, none of those attempts to substitute hAM have been translated inti clinical use.We have successfully used hAM as substrate and delivery platform in preclinical research, both in vitro and in vivo models of stem cell deficiency, and in the two clinical trials that have been completed and published, with both cultivated epithelial cells from the limbal niche and bone marrow‐derived mesenchymal stem cells.

Keratitis-ichthyosis-deafness syndrome: A comprehensive review of cutaneous and systemic manifestations.

Keratitis-ichthyosis-deafness syndrome is a rare genetic disease presenting with cutaneous, ocular, and otic defects. This comprehensive review provides insight into the clinical presentations, highlighting the cutaneous manifestations including histopathology and treatment options.

OTX2 duplications: a recurrent cause of oculo-auriculo-vertebral spectrum

BackgroundOculo-auriculo-vertebral spectrum (OAVS) is the second most common cause of head and neck malformations in children after orofacial clefts. OAVS is clinically heterogeneous and characterised by a broad range of...

Chromatin remodeler Chd7 regulates photoreceptor development and outer segment length

Mutations in the chromatin remodeling factor CHD7 are the predominant cause of CHARGE syndrome, a congenital disorder that frequently includes ocular coloboma. Although CHD7 is known to be required for proper ocular morphogenesis, its role in retinal development has not been thoroughly investigated. Given that individuals with CHARGE syndrome can experience visual impairment even in the absence of coloboma, a better understanding of CHD7 function in the retina is needed. In this study, we characterized the expression pattern of Chd7 in the developing zebrafish and mouse retina and documented ocular and retinal phenotypes in Chd7 loss-of-function mutants. Zebrafish Chd7 was expressed throughout the retinal neuroepithelium when retinal progenitor cells were actively proliferating, and later in subsets of newly post-mitotic retinal cells. At stages of retinal development when most retinal cell types had terminally differentiated, Chd7 expression remained strong in the ganglion cell layer and in some cells in the inner nuclear layer. Intriguingly, strong expression of Chd7 was also observed in the outer nuclear layer where it was co-expressed with markers of post-mitotic cone and rod photoreceptors. Expression of mouse CHD7 displayed a similar pattern, including expression in the ganglion cells, subsets of inner nuclear layer cells, and in the distal outer nuclear layer as late as P15. Two different mutant chd7 zebrafish lines were characterized for ocular and retinal defects. These mutants displayed microphthalmia, reduced numbers of cone photoreceptors, and truncated rod and cone photoreceptor outer segments. Reduced cone photoreceptor number and abnormal outer segments were also observed in heterozygous Chd7 mutant mice. Taken together, our results in zebrafish and mouse reveal a conserved, previously undescribed role for Chd7 in retinal development and photoreceptor outer segment morphogenesis. Moreover, our work suggests an avenue of future investigation into the pathogenesis of visual system defects in CHARGE syndrome.

Pathological Impact and Disease Burden of Human Onchocerciasis in Endemic Areas of Delta State, Nigeria

Background to the Study/Aim: The context of onchocerciasis being one of the neglected tropical diseases (NTDs) in Nigeria; and the predicted increase in the rate of spread of tropical diseases and vectors to higher altitude, as a result of climate change and global warming, underscores the need for more studies on the disease. Thus, this research was conducted to examine the pathological impact and disease burden of human onchocerciasis on the infected in endemic communities in three local government areas of Delta State, Nigeria.
 Materials and Methods: The study was carried out in two phases. The first phase involved four stages. Stage one was visual acuity test on those who volunteered to take part in the research. Stage two was the physical examination of individuals for characteristic onchocercal lesions. The third stage was the collection of skin snips from individuals while the fourth stage was microscopic examination of the skin snips for microfilariae of Onchocerca volvulus. The second phase examined the impact of the disease and was carried out with the aid of a structured questionnaire.
 Results: The results showed that human onchocerciasis existed in the study area. Out of the 1,201 persons, comprising of 826 (68.8%) males and 375 (31.2%) females examined, 138 were positive for the onchocercal parasite. The infected, consisted of 101 (12.2%) males and 37 (9.9%) females. Generally, infected persons had manifestations ranging from ocular defects, visual problems to skins disfiguration.
 Conclusion: In addition to the administration of ivermectin and vector control, psychosocial and economic needs of the infected should be addressed through counseling and offering of palliating assistance to reduce their economic problems and give them feeling of independence.

MiR92b-3p synthetic analogue impairs zebrafish embryonic development, leading to ocular defects, decreased movement and hatching rate, and increased mortality

The aim of this study was to examine the effect of microRNA 92b-3p (MiR92b-3p) overexpression on the embryonic development of zebrafish. A synthetic MiR92b-3p analogue (mirVana™ mimic, in vivo-ready) was injected at doses up to 5 ng/embryo into the yolk sac of embryos (2–16 cell stage). At 24 h post fertilization (hpf), the locomotor activity of the embryos was measured, and after hatching (72 hpf), the rates of malformation occurrence, hatching, and mortality were determined. Next, the larvae were fixed for histological and molecular examinations. Exposure to the MiR92b-3p mimic impaired embryonic development, leading to increased occurrence of malformations (i.e., pericardial edema, spine curvature, smaller eyes), decreased locomotor activity and hatching rate, and increased mortality. Importantly, the mimic affected retinal differentiation and lens formation during zebrafish embryogenesis, which suggests that MiR92b-3p could be an important factor in the regulation of fish embryogenesis and ocular development. The expression level of MiR92b-3p was substantially higher in the exposed larvae than in the untreated larvae, indicating that the mimic was successfully delivered to the zebrafish. Although screening of potential MiR92b-3p target genes suggested some changes in their expression levels, these results were inconclusive. Together, this study indicates that MiR92b-3p mimic impairs zebrafish embryonic development, and further research is necessary to identify the MiR92b-3p–regulated cell pathways involved in the impairment of the fish’s development.

An epiphanic case of X-linked Alport syndrome caused by a hitherto unreported COL4A5 gene mutation

Alport Syndrome (AS) is an inherited glomerular disease, which invariably progresses to End Stage Kidney Disease (ESRD). It can be associated with hearing impairment and ocular defects. The disease can be X-linked caused by mutations in the Type 4 Collagen alpha 5 chain (COL4A5), Autosomal Recessive (ARAS) or Autosomal Dominant (ADAS) caused by mutations in the Type 4 Collagen alpha 3 chain (COL4A3) or alpha 4 chain (COL4A4). We report a novel mutation in COL4A5 Gene causing XLAS resulting in Chronic Kidney Disease in a 34-year-old male. Whole genome sequencing of the patient, showed hemizygous variant (c.1690G>C, p. Gly564Arg) in the COL4A5 gene. The same variant was detected in his mother and his only daughter establishing that the mutation is pathogenic.

A Comparison of the Incidence and Type of Ocular Motility Defects in Patients Presenting to Birmingham Midland Eye Centre Emergency Department during 2019 and 2020 to Assess the Impact of the Covid-19 Pandemic.

Aim:This audit aimed to investigate whether COVID-19 had any impact on the incidence and type of ocular motility defects in patients presenting to Birmingham Midland Eye Centre (BMEC) Emergency Department (ED) during the COVID-19 pandemic in 2020 compared to the previous year.Methods:Medical records were reviewed for all patients presenting to BMEC ED during 2019 and 2020. Patients were classified depending on their diagnosis. The incidence and classification of ocular motility defect were analysed. Factors considered during analysis were number of presentations by year and month; COVID-19 tests; and pre-existing conditions.Results:Two hundred and twenty-one patients presented in 2019, and 260 patients in 2020, an increase in incidence of 17.6% was observed. One hundred and eighty-five patients were classified with new-onset neurogenic conditions in 2019, and 222 patients in 2020, an increase of 20.0%. In 2020, most patients presented in July, November, and December. Overall, there was a 91.3% increase in new-onset fourth cranial nerve palsies in 2020. Fifty-seven patients in 2020 had a Polymerase Chain Reaction COVID-19 test, of these 5 were COVID-19 positive.Conclusion:There was a higher incidence of ocular motility defects in 2020 compared to 2019. The majority of ocular motility defects were classified as neurogenic. It is difficult to attribute this increase to COVID-19 due to lack of testing and results, and confounding variables such as pre-existing conditions and lockdown restrictions. Some potential explanations for the change in presentations across the year of 2020 are proposed.