Amaurosis congénita de Leber RPE-65, seguimiento a 7 años.

Leber congenital amaurosis is a retinal dystrophy with several forms of presentation due to its genetic variability. Case of a female girl followed up from 4 to 11 years old is presented, with positive clinical data of nyctalopia, myopia and choroid ocular fundus. Electroretinogram was not measurable in all phases but diagnostic was confirmed by RPE65 mutation genetic study. RPE65 Leber congenital amaurosis is particularly important as it has been researched for a gene therapy treatment with good functional outcomes up to now, awaiting to offer hope and a better quality of life to people with this disease.

Characteristics of Vitamin A Deficiency Retinopathy at a Tertiary Referral Center in the United States.

PURPOSE: To explore the risk factors and fundus imaging features of vitamin A deficiency retinopathy (VADR) in an academic tertiary referral center in Atlanta, GA, United States, and to propose guidance regarding diagnostic workup and management of affected patients. DESIGN: Single-center retrospective case series. SUBJECTS: Nine patients seen between 2015 and 2021 at the Emory Eye Center diagnosed with VADR. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: Baseline serum retinol level, Snellen visual acuity, multimodal fundus imaging findings, and electroretinography findings. RESULTS: Nine patients, 4 (44.4%) female, with a median (range) age of 68 (50-75) years were identified. The most common underlying etiologies for vitamin A deficiency included history of gastrointestinal surgery (55.6%), liver disease (44.4%), and nutritional depletion due to low-quality diet (44.4%). Only 1 (11.1%) patient had a history of bariatric surgery. Four (44.4%) patients were on some form of vitamin A supplementation before the diagnosis of VADR. Median (range) serum retinol level was 0.06 (< 0.06-0.19) mg/L. All patients had macular subretinal hyperreflective deposits resembling subretinal drusenoid deposits, although in some cases, these were scant and sparsely distributed. Six eyes of 3 patients with longstanding deficiency had defects in the external limiting membrane (ELM). Three of these eyes additionally had macular areas of complete retinal pigment epithelium and outer retinal atrophy (cRORA). Full-field electroretinography demonstrated severe rod dysfunction and mild to moderate cone system dysfunction. Many findings of VADR were reversible with vitamin A repletion. However, all eyes with ELM defects or cRORA had persistence or continued growth of these lesions. CONCLUSION: Vitamin A deficiency retinopathy is uncommon in the developed world. However, given that early intervention can lead to dramatic visual improvement and avoid potentially permanent retinal damage, retina specialists should be familiar with its clinical presentation. The presence of nyctalopia and subretinal hyperreflective deposits in a patient with a history of gastrointestinal surgery, liver disease, and/or poor diet can be suggestive of this diagnosis, even in the presence of ongoing vitamin A supplementation. Vitamin A supplementation can vary in route and dosage and can be tailored to the individual with serial testing of serum retinol. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Reversible Nyctalopia and Bilateral Optic Neuropathy due to Combined Vitamin A, Zinc, and Copper Deficiency: A Case Report.

Introduction: Combined nutritional deficiency is an uncommon cause of vision loss in the USA. Notably, vitamin A deficiency can produce nyctalopia but rarely causes bilateral central vision loss. The combination of these symptoms is unusual, although likely underreported. Case Presentation: We report an exceptionally rare case of bilateral central vision loss and nyctalopia caused by combined vitamin A, zinc, and copper deficiency, likely following bariatric surgery and alcohol use. Following mineral and vitamin supplementation, the patient's vision improved significantly and returned to baseline within 1 month. Vision loss resulting from this specific multicombination of vitamin and mineral deficiency has never been reported previously in the English-language ophthalmic literature. Conclusion: Given rising rates of bariatric surgery and alcohol use in the USA and abroad, clinicians should be aware that the combination of progressive nyctalopia and bilateral central vision loss may be produced by combined nutritional deficiency. Screening and supplementation of both vitamin and mineral deficiency may result in dramatic reversal of visual loss in such cases.

Dent disease presenting with nyctalopia and electroretinographic correlates of vitamin A deficiency.

Purpose: To report a unique case of Dent Disease presenting with nyctalopia associated with vitamin A deficiency and abnormal electroretinogram findings without prior systemic symptomatology. Observations: A 16-year-old male presented with a several month history of nyctalopia and peripheral vision deficits. Central visual acuity, anterior and posterior segment examinations, and macular optical coherence tomography were unremarkable. Electroretinogram (ERG) testing revealed a rod-cone dystrophic pattern, with further workup demonstrating serum vitamin A deficiency (VAD). Laboratory evaluation revealed renal dysfunction and proteinuria with a significantly elevated urinary retinol-binding protein (RBP). Kidney biopsy showed glomerular and tubular disease.Genetic screening for inherited renal disease was performed identifying a hemizygous pathogenic variant c.2152C>T (p.Arg718*) in the Chloride Voltage-Gated Channel 5 (CLCN5) gene, confirming the diagnosis of X-linked Dent Disease. Following vitamin A supplementation, our patient reported resolution of nyctalopia and reversal of abnormal ERG findings were demonstrated. Conclusions and Importance: To our knowledge, this is the first case in the literature describing Dent disease solely presenting with ophthalmic symptoms of nyctalopia and abnormal electroretinogram findings that later reversed with vitamin A repletion. This case stresses the importance for clinicians to consider renal tubular disorders in the differential for VAD.

Introduction and Discovery of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy. There are three main characteristics of RP: night blindness, retinal pigmentation, and visual field constriction. Among these three features, night blindness was the first to be discovered, which could be dated back to the ancient Egyptians at around 1500 BC. However, the night blindness described at that time was most likely associated with vitamin A deficiency rather than RP. Retinitis pigmentosa was first described in cadaver anatomic dissection before the invention of the ophthalmoscope. However, it was not linked to RP or night blindness. It was not until the invention of the ophthalmoscope that ophthalmologists could truly look into the eye and correlate the retinal pigmentation with clinical symptoms, such as night blindness and visual field constriction. In 1983, at a RP workshop that gathered together many experts, a consensus was reached regarding the terminology and guidelines for the diagnosis of RP. In this chapter, we will introduce the history and discovery of RP along with its characteristics.

Concentric Reversible Visual Field Loss, Nyctalopia, and Dyschromatopsia with Ezetimibe Therapy.

This is a case of ezetimibe-induced concentric field loss, dyschromatopsia, and nyctalopia in a patient with no prior history of retinal dystrophy or drug hypersensitivity. A 55-year-old Caucasian woman presents with a 1-year history of increasing concentric visual field loss, nyctalopia, photophobia, and colour vision impairment. These symptoms correlated with the commencement of ezetimibe therapy 10 mg daily for hypercholesterolaemia. She demonstrated repeatable bilateral visual field constriction on 30-2 Humphrey visual filed testing and colour vision impairment on Ishihara plates (OD: 1/17, OS: 1/17). Biochemical and radiological screening for carcinoma-associated retinopathy was unremarkable. A working diagnosis of drug-induced rod-cone dysfunction was made. Her visual symptoms and field changes completely resolved 3 months after cessation of ezetimibe therapy. This case suggests that ezetimibe is a potential cause of rod-cone dysfunction and should be considered as a differential in patients with new unexplained visual symptoms.

Visual Function Tests.

Inherited retinal diseases (IRDs), including retinitis pigmentosa, have devastating consequences for the visual function of affected individuals. Chief among these are a gradual loss of visual field, visual acuity, and night vision (otherwise known as nyctalopia). These changes often occur slowly, over a course of decades. Objective modalities for assessing these many aspects of visual function are crucial, not only to the monitoring of disease progression but, in recent years, also to evaluating the efficacy or lack thereof of new therapeutic interventions in the setting of clinical trials. This chapter will provide descriptions of these valuable assessment modalities, alongside discussions of their advantages and limitations in the context of serving those afflicted by IRDs.

Nyctalopia and Xerophthalmia in a Patient With Crohn's Induced Vitamin A Deficiency.

The vitamin A derivative, retinal, plays a pivotal role in scotopic and color vision. Although vitamin A deficiency (VAD) presents as a common cause of preventable blindness in areas with poor access to foods rich in vitamin A, it is uncommon in developed countries. We present a 56-year-old male with a history of Crohn's disease and pancreatitis who was referred to our ophthalmology office by optometry for severe dry eyes. He complained of a two-year history of constant blurred vision and nyctalopia. He stated that "images just appear dark." Examination demonstrated mildly decreased visual acuity with severe ocular surface disease and characteristic Bitot's spots in both eyes. Based on the patient's history and physical, a diagnosis of xerophthalmia in the setting of VAD was made. The patient was referred to his internist, he then underwent further evaluation and treatment with vitamin A intramuscular injections post-diagnosis.  This case illustrates the potential for VAD secondary to malabsorption from Crohn's disease and the importance of taking a full patient history so systemic causes of ophthalmic symptoms may be promptly identified and treated. VAD is extremely rare in the United States, however, patients at risk for VAD may benefit from regular vitamin A level checks and ophthalmologic evaluation.

Beaded Pearls Appearance in Syphilitic Chorioretinitis.

PURPOSE: To report an atypical case of bilateral syphilitic chorioretinitis. METHODS: A case report. RESULTS: A young male presented with bilateral pigmentary retinal changes along with multifocal chorioretinal lesions along the blood vessels giving a "beaded pearl" appearance. He was a hitherto undiagnosed case of human immunodeficiency virus infection and was diagnosed to have syphilis. He had a favourable visual and anatomical outcome following treatment. CONCLUSION: Multifocal chorioretinal lesions along blood vessels forming a "beaded pearls" appearance can be a rare and unique presentation of syphilis.

Accessory iris membranes: Removing the veil.

PURPOSE: To report a case of a young adult with dense bilateral accessory iris membranes (AIMs). OBSERVATIONS: AIMs can influence vision by multiple mechanisms. We discuss clinical examination and imaging considerations that can help parse optical and refractive complications to better guide intervention discussions. We also describe our surgical approach and perioperative management to help minimize trauma to the eye and maximize favorable surgical outcomes in these cases. CONCLUSIONS AND IMPORTANCE: This case highlights the excellent symptomatic, visual acuity and stereopsis gains that can be achieved following surgical intervention for this clinical entity, even in older patients.

Efficient measurements for the dynamic range of human lightness perception.

PURPOSE: Patients with an eye disease often report nyctalopia, hemianopia, and/or photophobia. We hypothesized that such symptoms are related to the disease impacting the dynamic range of lightness perception (DRL). However, there is currently no standardized approach for measuring DRL for clinical use. We developed an efficient measurement method to estimate DRL. STUDY DESIGN: Clinical trial METHODS: Fifty-five photophobic patients with eye disease and 46 controls participated. Each participant judged the appearance of visual stimuli, a thick bar with luminance that gradually changed from maximum to minimum was displayed on uniform background. On different trials the background luminance changed pseudo-randomly between three levels. The participants repeatedly tapped a border on the bar that divided the appearance of grayish white/black and perfect white/black. We defined the DRL as the ratio between the luminance values at the tapped point of the border between gray and white/black. RESULTS: The mean DRL of the patients was approximately 15 dB, significantly smaller than that of the controls (20 dB). The center of each patient's DRL shift depending on background luminance, which we named index of contextual susceptibility (iCS), was significantly larger than controls. The DRL of retinitis pigmentosa was smaller than controls for every luminance condition. Only the iCS of glaucoma was significantly larger than controls. CONCLUSIONS: This measurement technique detects an abnormality of the DRL. The results support our hypothesis that the DRL abnormality characterizes lightness-relevant symptoms that may elucidate the causes of nyctalopia, hemeralopia, and photophobia.

Visual Snow: A Case Series from Israel.

Our aim was to examine the symptoms and clinical characteristics of visual snow in a group of 6 patients from a Department of Ophthalmology and a Department of Neurology. Visual snow is now recognized as a true physiological disorder. Previously, physicians unaware of this syndrome may have misinterpreted its symptoms as a persistent visual aura. By promoting awareness of this syndrome, greater quantitative and qualitative research may expand our understanding and treatment of this disorder.

Intravenous Immunoglobulin for Management of Non-paraneoplastic Autoimmune Retinopathy.

PURPOSE: To report a case of non-paraneoplastic autoimmune retinopathy (npAIR) treated with intravenous immunoglobulin (IVIG). CASE REPORT: A 12-year-old boy presented with progressive visual field loss, nyctalopia, and flashing for three months. He had suffered from common cold two weeks before the onset of these symptoms. On the basis of clinical history and paraclinical findings, he was diagnosed with npAIR, and IVIG without immunosuppressive therapy was started. During the one-year follow-up period after the first course of IVIG, flashing disappeared completely. Visual acuity remained 10/10, but nyctalopia did not improve. Multimodal imaging showed no disease progression. CONCLUSION: Although established retinal degenerative changes seem irreversible in npAIR, IVIG may be a suitable choice to control the disease progression.

Outer retina changes on optical coherence tomography in vitamin A deficiency.

BACKGROUND: Vitamin A deficiency is rare in the United States and can be missed in patients with malabsorption syndromes without a high dose of suspicion. Ocular complications of hypovitaminosis A include xerosis and nyctalopia, and to a lesser extent reduction in visual acuity and color vision. Outer retinal changes, as seen on spectral domain optic coherence tomography (SD-OCT), in patients with vitamin A deficiency have previously not been documented. CASE PRESENTATION: We present two cases with symptoms of severe nyctalopia who were subsequently diagnosed with severe Vitamin A deficiency and their unique findings on SD-OCT of outer nuclear layer diffuse thinning with irregular appearance of the interdigitating zone and the ellipsoid zone as well as normalization after vitamin A supplementation. CONCLUSIONS: Outer nuclear layer thinning and disruption of the outer retinal bands on SD-OCT are reversible with correction of vitamin A deficiency. Improvement in visual acuity, color vision, and nyctalopia are possible with early diagnosis and appropriate treatment.

Diagnosis of an X-linked type 2 congenital stationary night blindness using electroretinography and CACNA1F sequencing. / Diagnóstico de un caso de ceguera nocturna estacionaria congénita tipo 2 ligada al cromosoma X mediante electrorretinografía y secuenciación del gen CACNA1F.

A 4-year-old boy, with no history of relevance, presented with bilateral visual impairment, more so in scotopic conditions, and did not improve with optical correction. No significant funduscopic abnormalities were seen, leading to a suspicion of retinal dystrophy. Sequencing of the CACNA1F gene detected the c.3081C>A (p.Tyr1027Ter) mutation, which had occurred de novo in the patient's mother. This mutation, in the aforementioned clinical context, and with a compatible electronegative pattern, establishes the diagnosis of X-linked type 2 congenital stationary night blindness. Electrophysiology and genetic testing should be part of the diagnostic protocol for any unexplained loss of vision in children. The description, nomenclature and classification of hereditary retinal dystrophies based on their genotypic and electroretinograpic characteristics, avoids diagnostic errors due to their usual clinical and phenotypic overlap.

Typical electronegative electroretinography and nyctalopia as a presenting feature of systemic malignant melanoma.

We report a unique case of a female who presented with unilateral disk edema, melanoma-associated retinopathy symptoms, and suggestive electroretinography findings preceding a diagnosis of metastatic melanoma of the pelvis. A 63-year-old female presented with complaints of seeing shimmering lights and nyctalopia, and underwent an extensive ophthalmological and electrophysiological examination. Best-corrected visual acuity was 20/20 in both eyes. Visual fields showed relative central scotomata and concentric narrowing. Slit-lamp and fundus examinations were normal. Rod-specific electroretinography responses were severely reduced, with electronegative maximal combined rod-cone responses and delayed cone responses with normal amplitude. Melanoma-associated retinopathy was suspected. Extensive systemic and internal evaluation revealed occult metastatic melanoma of the pelvis of unknown primary site.

Whole genome sequencing reveals novel mutations causing autosomal dominant inherited macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a common sight threatening condition. However, there are a number of monogenic macular dystrophies that are clinically similar to AMD, which can potentially provide pathogenetic insights. METHODS: Three siblings from a non-consanguineous Greek-Cypriot family reported central visual disturbance and nyctalopia. The patients had full ophthalmic examinations and color fundus photography, spectral-domain ocular coherence tomography and scanning laser ophthalmoscopy. Targeted polymerase chain reaction (PCR) was performed as a first step to attempt to identify suspected mutations in C1QTNF5 and TIMP3 followed by whole genome sequencing. RESULTS: The three patients were noted to have symptoms of nyctalopia, early paracentral visual field loss and, in older patients, central vision loss. Imaging identified pseudodrusen, retinal atrophy and RPE-Bruch's membrane separation. Whole genome sequencing of the proband revealed two novel heterozygous variants in C1QTNF5, c.556C>T, and c.569C>G. The mutation segregated with disease in this family, occurred in cis, and resulted in missense amino acid changes P186S and S190W in C1QTNF5. In silico modeling of the variants revealed that the S190W mutations was likely to have the greatest pathologic effect and that the combination of the mutations was likely to have an additive effect. CONCLUSIONS: The novel mutations in C1QTNF5 identified here expand the genotypic spectrum of mutations causing late-onset retinal dystrophy.

Stem Cell Ophthalmology Treatment Study: bone marrow derived stem cells in the treatment of Retinitis Pigmentosa.

BACKGROUND: Seventeen patients with bilateral visual loss due to Retinitis Pigmentosa (RP) underwent autologous bone marrow derived stem cell (BMSC) treatment within the Stem Cell Ophthalmology Treatment Study (SCOTS and SCOTS 2). Both are National Institutes of Health (NIH) and Office of Human Research Protection (OHRP) compliant Institutional Review Board (IRB) approved clinical studies utilizing using autologous BMSC in the treatment of retinal and optic nerve diseases that meet inclusion criteria. METHODS: The average age of the patients treated was 48.8 years. The average duration of disease prior to treatment was 27.6 years and ranged from 4 to approximately 60 years. Affected eyes were treated with either retrobulbar, subtenons and intravenous BMSC or retrobulbar, subtenons, intravitreal and intravenous. Follow up was provided a minimum of 6 months. The primary outcome was visual acuity as measured by Snellen or converted to LogMAR. RESULTS: Following therapy in SCOTS or SCOTS 2, 11 patients (64.7%) showed improved binocular vision averaging 10.23 lines of Snellen acuity per eye over pre-treatment acuity; 8 patients (35.3%) remaining stable over the follow up period; no patients experiencing loss of overall acuity. In 33 treated eyes, 15 eyes (45.5%) improved an average of 7.9 lines of Snellen acuity, 15 eyes (45.5%) remained stable, and 3 eyes (9%) worsened by an average of 1.7 lines of Snellen acuity. Improvements ranged from 1 to 27 lines of vision. Using the LogMAR Scale and calculating delta as a ratio to pre-treatment vision in improved eyes, acuity improvement ranged from 23% to 90% with an average of 40.9% visual acuity improvement over baseline vision. Evaluation of all patients and eyes capable of LogMAR vision showed an average of 31% improvement in vision over baseline. Findings were of statistical significance (P=0.016). There were no surgical complications. CONCLUSIONS: The BMSC protocols of the SCOTS achieved meaningful visual acuity improvements or stability in RP that were of statistical significance. Duration of disease did not appear to affect the ability of eyes to respond. Safety was confirmed. Possible mechanisms by which improvement occurred may include transdifferentiation of BMSC into Neuronal Nuclei (NeuN) positive cells, BMSC paracrine secretions or neurotrophic factors and hormones, transfer of mitochondria, release of messenger RNA or other compounds via exosomes or microvesicles. Given the successful outcome in this otherwise progressive condition, consideration should be given to providing this treatment option.

Keeping an Eye on Bardet-Biedl Syndrome: A Comprehensive Review of the Role of Bardet-Biedl Syndrome Genes in the Eye.

Upwards of 90% of individuals with Bardet-Biedl syndrome (BBS) display rod-cone dystrophy with early macular involvement. BBS is an autosomal recessive, genetically heterogeneous, pleiotropic ciliopathy for which 21 causative genes have been discovered to date. In addition to retinal degeneration, the cardinal features of BBS include obesity, cognitive impairment, renal anomalies, polydactyly, and hypogonadism. Here, we review the genes, proteins, and protein complexes involved in BBS and the BBS model organisms available for the study of retinal degeneration. We include comprehensive lists for all known BBS genes, their known phenotypes, and the model organisms available. We also review the molecular mechanisms believed to lead to retinal degeneration. We provide an overview of the mode of inheritance and describe the relationships between BBS genes and Joubert syndrome, Leber Congenital Amaurosis, Senior-Løken syndrome, and non-syndromic retinitis pigmentosa. Finally, we propose ways that new advances in technology will allow us to better understand the role of different BBS genes in retinal formation and function.

Unilateral retinitis pigmentosa. A case report. / Retinitis pigmentosa unilateral a propósito de un caso.

CLINICAL CASE: A 27-year-old woman with a history of nyctalopia and constriction of visual field of the right eye. The ophthalmological examination showed a visual field and electroretinogram that were compatible with unilateral retinitis pigmentosa (RP). After a one year follow-up, the unilateral condition remained. DISCUSSION: Unilateral retinitis pigmentosa is a rare condition, with a frequency between 0.2%-5% of the RP. It mainly affects women and older age groups than bilateral RP. For a definitive diagnosis, it is necessary to have a funduscopy and electroretinogram (ERG) altered unilaterally, and exclude infectious, inflammatory, and vascular causes.