OUTCOMES OF INFECTIOUS PANUVEITIS ASSOCIATED WITH SIMULTANEOUS MULTI-POSITIVE OCULAR FLUID POLYMERASE CHAIN REACTION.

PURPOSE: To evaluate features of infectious panuveitis associated with multiple pathogens detected by ocular fluid sampling. METHODS: Single-center, retrospective, consecutive case series of patients with aqueous/vitreous polymerase chain reaction testing with >1 positive result in a single sample from 2001 to 2021. RESULTS: Of 1,588 polymerase chain reaction samples, 28 (1.76%) were positive for two pathogens. Most common pathogens were cytomegalovirus (n = 16, 57.1%) and Epstein-Barr virus (n = 13, 46.4%), followed by varicella zoster virus (n = 8, 28.6%), Toxoplasma gondii (n = 6, 21.4%), herpes simplex virus 2 (n = 6, 21.4%), herpes simplex virus 1 (n = 6, 21.4%), and Toxocara (n = 1, 3.6%). Mean initial and final visual acuity (logarithm of the minimum angle of resolution) were 1.3 ± 0.9 (Snellen ∼20/400) and 1.3 ± 1.1 (Snellen ∼20/400), respectively. Cytomegalovirus-positive eyes (n = 16, 61.5%) had a mean final visual acuity of 0.94 ± 1.1 (Snellen ∼20/175), whereas cytomegalovirus-negative eyes (n = 10, 38%) had a final visual acuity of 1.82 ± 1.0 (Snellen ∼20/1,320) ( P < 0.05). Main clinical features included intraocular inflammation (100%), retinal whitening (84.6%), immunosuppression (65.4%), retinal hemorrhage (38.5%), and retinal detachment (34.6%). CONCLUSION: Cytomegalovirus or Epstein-Barr virus were common unique pathogens identified in multi-PCR-positive samples. Most patients with co-infection were immunosuppressed with a high rate of retinal detachment and poor final visual acuity. Cytomegalovirus-positive eyes had better visual outcomes compared with cytomegalovirus-negative eyes.

Lymphoepithelioma-like carcinoma of the eyelid and ocular adnexa.

A 93-year-old Caucasian woman presented to clinic for evaluation of a progressively enlarging left eyelid mass. Exam revealed a large, indurated, poorly mobile mass involving the left upper eyelid. Imaging demonstrated a crescentic enhancing soft-tissue mass in the left upper eyelid without evidence of deeper orbital involvement. Biopsy demonstrated tumor nests positive for cytokeratin AE1/AE3, P63, and P40 consistent with a diagnosis of eyelid lymphoepithelioma-like carcinoma (LELC). The patient underwent surgical resection with subsequent left upper eyelid reconstruction and adjuvant radiation. She had no clinical evidence of disease recurrence at follow-up. LELC is an uncommon tumor that rarely involves the eyelid and ocular adnexa. Early identification is important due to its malignant potential, as the majority of previously reported cases demonstrated local or distant metastatic spread. Future studies are needed to determine the optimum treatment regimen for this rare periorbital neoplasm.

Phenotypic expansion and progression of SPATA7-associated retinitis pigmentosa.

PURPOSE: To report an unusual phenotype of retinitis pigmentosa (RP) caused by compound heterozygous mutations in SPATA7, and describe the progression over a two year follow-up period. METHODS: Retrospective case study. RESULTS: A 63-year-old man with a long history of nyctalopia, progressive visual field constriction, and a recent subacute decrease in visual acuity of the left eye presented for evaluation of a suspected retinal degeneration. Multimodal retinal imaging and functional assessment with full-field electroretinogram suggested a severe rod-cone dysfunction masquerading as a choroideremia-like phenotype. A vitreous opacity was found to explain recent changes in the left eye and a 25-guage vitrectomy and membrane peel was performed, yielding no change in visual acuity. Whole-exome sequencing revealed compound heterozygous variants in SPATA7 that were predicted to be pathogenic. CONCLUSIONS: Compound heterozygous c.1100A > G, p.(Y367C) and c.1102_1103delCT, p.(L368Efs*4) variants in SPATA7 manifest as an unusual RP phenotype in this case, showing extensive choroidal sclerosis and retinal pigment epithelium (RPE) atrophy with evidence of progression over two years on multimodal imaging.

Congenital grouped albinotic spots of the retinal pigment epithelium in a patient with hemihypertrophy and café au lait spots.

PURPOSE: To describe the finding of circularly grouped hypomelanotic spots in the central macula of a patient with syndromic characteristics. METHODS: Case report of a patient with albinotic spots grouped within the macula, café au lait spots, and left-sided hemihypertrophy. RESULTS: A 15-year-old boy presented with hypomelanotic spots which were hyperautofluorescent on fundus autofluorescence imaging with no disruption of the retinal laminae or photoreceptor inner and outer segment (IS/OS) junction on spectral domain optical coherence tomography. His developmental history included hemihypertrophy, café au lait spots over his axilla and extremities, and surgically corrected left-sided cryptorchidism. Other ocular history included resolved convergence insufficiency and red-green color blindness. CONCLUSIONS: It is essential to recognize that circularly grouped hypomelanotic spots are a benign condition. The location and arrangement of the hypomelanotic spots were atypical for congenital grouped albinotic spots of the retinal pigment epithelium (CGAS) as they were grouped within the macula in addition to a more characteristic linear "bear track" formation in the periphery. To the authors' knowledge, this is the first report of CGAS present in a patient with hemihypertrophy, café au lait spots, and cryptorchidism and may represent a novel syndromic association.

Mitochondrial A3243G mutation results in corneal endothelial polymegathism.

PURPOSE: The mitochondrial DNA point mutation A3243G leads to a spectrum of syndromes ranging from MIDD to MELAS. Ocular manifestations include pattern macular dystrophy and concentric perifoveal atrophy. Given the high metabolic demand of corneal endothelial cells, we performed specular biomicroscopy analysis in patients harboring the mitochondrial DNA point mutation A3243G to assess for the associated presence of corneal endothelial abnormalities. METHODS: We present a case series with participants from two institutions. Patients diagnosed with macular dystrophy associated with MIDD or MELAS, and the mitochondrial DNA point mutation A3243G were recruited. Exclusion criteria included a prior diagnosis, or a positive family history, of endothelial corneal dystrophy. Slit-lamp corneal examination and specular biomicroscopy were performed. Corneal endothelial cell count, cell size and polymegathism, and central corneal thickness were assessed. Patients diagnosed with MIDD or MELAS based on clinical history and examination were genetically tested for the mitochondrial DNA point mutation A3243G using pyrosequencing. RESULTS: Five patients (two male and three female participants) from five different families, and with different ethnic backgrounds, met the inclusion criteria. Their ages ranged from 41 to 60 years. Corneal endothelial changes observed using slit-lamp examination were primarily mild to rare guttata. Specular biomicroscopy displayed mainly polymegathism associated with guttata. The average endothelial cell count was 2358 ± 456 cells per mm2, the average endothelial cell size was 442 ± 103 µm2 and the average central corneal thickness (CCT) was 551 ± 33 µm. These values were similar to that of the average population. The average coefficient of variation (COV), an index of heterogeneity in cell size, was 42.0 ± 4.1%. When compared to the average population, the average COV was significantly higher than predicted for the patients' age. None of the patients had signs of corneal edema. One patient had a pre-Descemet's opacity. CONCLUSIONS: In patients with the mitochondrial DNA point mutation A3243G, corneal endothelial polymegathism is present. This is mainly associated with mild guttata. The findings of corneal endothelial cell polymegathism may be a biomarker of mitochondrial disease, specifically in patients with the mitochondrial DNA A3243G mutation.

CRISPR applications in ophthalmologic genome surgery.

PURPOSE OF REVIEW: The present review seeks to summarize and discuss the application of clustered regularly interspaced short palindromic repeats (CRISPR)-associated systems (Cas) for genome editing, also called genome surgery, in the field of ophthalmology. RECENT FINDINGS: Precision medicine is an emerging approach for disease treatment and prevention that takes into account the variability of an individual's genetic sequence. Various groups have used CRISPR-Cas genome editing to make significant progress in mammalian preclinical models of eye disease, the basic science of eye development in zebrafish, the in vivo modification of ocular tissue, and the correction of stem cells with therapeutic applications. In addition, investigators have creatively used the targeted mutagenic potential of CRISPR-Cas systems to target pathogenic alleles in vitro. SUMMARY: Over the past year, CRISPR-Cas genome editing has been used to correct pathogenic mutations in vivo and in transplantable stem cells. Although off-target mutagenesis remains a concern, improvement in CRISPR-Cas technology and careful screening for undesired mutations will likely lead to clinical eye therapeutics employing CRISPR-Cas systems in the near future.

CRISPR in the Retina: Evaluation of Future Potential.

Clustered regularly interspaced short palindromic repeats (CRISPR) has been gaining widespread attention for its ability for targeted genome surgery. In treating inherited retinal degenerations, gene therapies have had varied results; the ones effective in restoring eye sight are limited by transiency in its effect. Genome surgery, however, is a solution that could potentially provide the eye with permanent healthy cells. As retinal degenerations are irreversible and the retina has little regenerative potential, permanent healthy cells are vital for vision. Since the retina is anatomically accessible and capable of being monitored in vivo, the retina is a prime location for novel therapies. CRISPR technology can be used to make corrections directly in vivo as well as ex vivo of stem cells for transplantation. Current standard of care includes genetic testing for causative mutations in expectation of this potential. This chapter explores future potential and strategies for retinal degenerative disease correction via CRISPR and its limitations.

Blood-spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice.

Humans with ALS and transgenic rodents expressing ALS-associated superoxide dismutase (SOD1) mutations develop spontaneous blood-spinal cord barrier (BSCB) breakdown, causing microvascular spinal-cord lesions. The role of BSCB breakdown in ALS disease pathogenesis in humans and mice remains, however, unclear, although chronic blood-brain barrier opening has been shown to facilitate accumulation of toxic blood-derived products in the central nervous system, resulting in secondary neurodegenerative changes. By repairing the BSCB and/or removing the BSCB-derived injurious stimuli, we now identify that accumulation of blood-derived neurotoxic hemoglobin and iron in the spinal cord leads to early motor-neuron degeneration in SOD1(G93A) mice at least in part through iron-dependent oxidant stress. Using spontaneous or warfarin-accelerated microvascular lesions, motor-neuron dysfunction and injury were found to be proportional to the degree of BSCB disruption at early disease stages in SOD1(G93A) mice. Early treatment with an activated protein C analog restored BSCB integrity that developed from spontaneous or warfarin-accelerated microvascular lesions in SOD1(G93A) mice and eliminated neurotoxic hemoglobin and iron deposits. Restoration of BSCB integrity delayed onset of motor-neuron impairment and degeneration. Early chelation of blood-derived iron and antioxidant treatment mitigated early motor-neuronal injury. Our data suggest that BSCB breakdown contributes to early motor-neuron degeneration in ALS mice and that restoring BSCB integrity during an early disease phase retards the disease process.

Gene and cell-based therapies for inherited retinal disorders: An update.

Retinal degenerations present a unique challenge as disease progression is irreversible and the retina has little regenerative potential. No current treatments for inherited retinal disease have the ability to reverse blindness, and current dietary supplement recommendations only delay disease progression with varied results. However, the retina is anatomically accessible and capable of being monitored at high resolution in vivo. This, in addition to the immune-privileged status of the eye, has put ocular disease at the forefront of advances in gene- and cell-based therapies. This review provides an update on gene therapies and randomized control trials for inherited retinal disease, including Leber congenital amaurosis, choroideremia, retinitis pigmentosa, Usher syndrome, X-linked retinoschisis, Leber hereditary optic neuropathy, and achromatopsia. New gene-modifying and cell-based strategies are also discussed. © 2016 Wiley Periodicals, Inc.

A lipoprotein receptor cluster IV mutant preferentially binds amyloid-ß and regulates its clearance from the mouse brain.

Soluble low density lipoprotein receptor-related protein-1 (sLRP1) binds ~70% of amyloid ß-peptide (Aß) in human plasma. In Alzheimer disease (AD) and individuals with mild cognitive impairment converting to AD, plasma sLRP1 levels are reduced and sLRP1 is oxidized, which results in diminished Aß peripheral binding and higher levels of free Aß in plasma. Experimental studies have shown that free circulating Aß re-enters the brain and that sLRP1 and/or its recombinant wild type cluster IV (WT-LRPIV) prevent Aß from entering the brain. Treatment of Alzheimer APPsw(+/0) mice with WT-LRPIV has been shown to reduce brain Aß pathology. In addition to Aß, LRPIV binds multiple ligands. To enhance LRPIV binding for Aß relative to other LRP1 ligands, we generated a library of LRPIV-derived fragments and full-length LRPIV variants with glycine replacing aspartic acid residues 3394, 3556, and 3674 in the calcium binding sites. Compared with WT-LRPIV, a lead LRPIV-D3674G mutant had 1.6- and 2.7-fold higher binding affinity for Aß40 and Aß42 in vitro, respectively, and a lower binding affinity for other LRP1 ligands (e.g. apolipoprotein E2, E3, and E4 (1.3-1.8-fold), tissue plasminogen activator (2.7-fold), matrix metalloproteinase-9 (4.1-fold), and Factor Xa (3.8-fold)). LRPIV-D3674G cleared mouse endogenous brain Aß40 and Aß42 25-27% better than WT-LRPIV. A 3-month subcutaneous treatment of APPsw(+/0) mice with LRPIV-D3674G (40 µg/kg/day) reduced Aß40 and Αß42 levels in the hippocampus, cortex, and cerebrospinal fluid by 60-80% and improved cerebral blood flow responses and hippocampal function at 9 months of age. Thus, LRPIV-D3674G is an efficient new Aß clearance therapy.

Cytomegalovirus Retinitis Associated With Intravitreal Dexamethasone Implant Injection.

Purpose: To describe an immunocompetent patient with cytomegalovirus (CMV) retinitis after dexamethasone implant injection and review previously documented cases. Methods: A review of case reports and literature was performed. Results: A 75-year-old man presented with acute decreased vision in the left eye. He had a vitrectomy and membrane peeling for an epiretinal membrane with recurrent cystoid macular edema and was receiving intravitreal dexamethasone implant injections at an outside hospital. The visual acuity in the left eye was hand motions, and an examination found patchy retinal whitening with hemorrhages. Aqueous polymerase chain reaction was positive for CMV. The laboratory evaluation was negative for immunodeficiencies. He was treated successfully with intravitreal and oral antivirals; however, his vision remained poor at most recent follow-up. A literature review found 8 previous cases of CMV retinitis after dexamethasone implant injection, although most had underlying immune dysregulation. Conclusions: CMV retinitis after intravitreal dexamethasone implant injection is rare. Awareness of this complication is essential because of the risk for devastating blindness.

Choroideremia presenting as vision loss secondary to choroidal neovascularization.

BACKGROUND: Choroidal neovascularization (CNV) is a rare complication of choroideremia that occurs secondary to relative atrophy of the retinal pigment epithelium and eventual rupture of Bruch's membrane. The ideal management of CNV in choroideremia is unclear. MATERIALS AND METHODS: Case report. OBSERVATIONS: A 14-year-old male with no known ocular history presented to the eye emergency department complaining of a central scotoma in the right eye for 4 days. He had no past medical history and family history was unremarkable for known ocular disease. Visual acuity was 20/70 in the right eye and 20/30 in the left eye. Posterior segment exam revealed chorioretinal atrophy extending from the outer macula to the midperiphery in both eyes. There was CNV with associated subretinal hemorrhage in the right eye. Optical coherence tomography demonstrated the presence of CNV with subretinal fluid in the right eye and parafoveal outer retinal atrophy in both eyes. Genetic testing revealed a hemizygous exon 2 deletion on the CHM gene, pathogenic for choroideremia. The patient received a total of 3 injections 4 weeks apart followed by 1 injection 6 weeks later with resolution of the subretinal hemorrhage and reduction in CNV size with improvement in visual acuity to 20/20 at last follow-up exam. CONCLUSIONS AND IMPORTANCE: Choroidal neovascularization is a rare cause of central vision loss in patients with choroideremia. In this report, we demonstrate a good functional and anatomic response to intravitreal bevacizumab in a 14-year-old patient with undiagnosed choroideremia who presented with CNV-induced central vision loss.

Coats-Like Presentation of Familial Exudative Vitreoretinopathy Associated With a Novel LRP5 Variant.

This report describes a unique case of a Coats-like presentation of familial exudative vitreoretinopathy in an 11-year-old girl. The patient was originally referred for evaluation of presumed Coats disease and presented with telangiectatic vessels, perivascular exudates, diffuse peripheral exudation, and intraretinal hemorrhages. Clinical and angiographical findings were consistent with familial exudative vitreoretinopathy, while genetic testing identified variants of uncertain significance in two associated genes, LRP5 and ZNF408. In silico analysis predicts the LRP5 variant to be pathogenic. Retinal vasculopathies often have phenotypic overlap, warranting angiographic examination of both eyes and genetic testing to uncover the correct diagnosis and guide proper treatment. [Ophthalmic Surg Lasers Imaging Retina 2024;55:462-466.].

Fluorescein Angiography Parameters in Premature Neonates.

Purpose: To describe fluorescein angiography (FA) parameters observed in premature neonates with retinopathy of prematurity (ROP). Design: Retrospective case series. Subjects: Patients with ROP who underwent FA imaging using Retcam at Holtz Children's Hospital from November 2014 to October 2022. Methods: Fluorescein angiography images of the included patients were analyzed with a focus on the timing of angiography phases, including choroidal flush, retinal, and recirculation phases. Gestational age, birth weight (BW), age at imaging, treatment choice, and any FA complications were documented. Main Outcome Measures: Dose of fluorescein administered, onset and duration of each angiography phase, and FA findings in ROP-treated patients. Results: A total of 72 images of 72 eyes were reviewed. Image quality was deemed suitable for inclusion in 64 eyes (88.9%) of 43 patients. The mean gestational age and BW at birth were 24.4 ± 1.9 weeks and 607.8 ± 141.3 g, respectively. The mean postmenstrual age at FA imaging was 50.5 ± 40.8 weeks. All eyes (100%) received treatment with intravitreal injection of anti-VEGF at a mean age of 35.5 ± 2.4 weeks. The onset and duration of angiography phases were relatively variable within the cohort. Choroidal flush occurred at a mean time of 12.2 seconds (range: 6-22 seconds). A subsequent retinal phase was documented at a mean time of 11.96 seconds (range: 3-22 seconds). Recirculation phase was complete at an average time of 2.15 minutes (range: 1-5.45 minutes) postfluorescein injection. None of patients developed allergic reactions to fluorescein injection, such as rash, respiratory distress, tachycardia, fever, or local injection site reactions. Conclusions: Angiographic phases on FA in preterm infants with ROP are variable and may occur earlier than the established references for adults. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Telomere Biology Disorders: Report on Clinical and Angiographic Findings.

PURPOSE: To evaluate the retinal vasculature in pediatric patients with telomere biology disorders (TBD). DESIGN: Retrospective consecutive case series. SUBJECTS: Pediatric patients with a diagnosis of TBD who underwent widefield fluorescein angiography (FA). METHODS: Electronic medical records of pediatric patients with TBD at a tertiary referral eye center were reviewed from January 2019 to July 2023. Vascular phenotype was assessed by reviewing FA images. MAIN OUTCOMES MEASURES: Incomplete peripheral vascularization, aneurysmal dilatation, terminal arborization, anastomotic loops, capillary dropout, neovascularization, tortuosity, leakage from tractional membranes, and blockage from hemorrhage. RESULTS: Fourteen eyes from 7 patients were included. All patients were genetically confirmed for TBD. The most common genetic variants were in CTC1 (5 patients; 71.4%), ACD (1 patient; 14.3%), and RTEL1 (1 patient; 14.3%). On FA, the most common findings were incomplete peripheral vascularization (14 eyes, 100%), aneurysmal dilatation (12 eyes, 85.7%), terminal arborization (12 eyes, 85.7%), anastomotic loops (12 eyes, 85.7%), capillary dropout (10 eyes, 71.4%), and neovascularization (9 eyes, 64.3%). Regarding treatment, laser photocoagulation (14 eyes, 100%), intravitreal bevacizumab injection (13 eyes, 92.6%), and sub-tenon's Kenalog (11 eyes, 78.6%) were utilized. All patients managed with laser photocoagulation and/or bevacizumab required multiple treatments. CONCLUSION: Our study describes a spectrum of vascular changes evidenced by widefield FA in pediatric patients with genetically confirmed TBD. Although further research is warranted to fully understand the etiology of these subtle vascular anomalies, widefield FA should be conducted in patients with genetically confirmed or suspected TBD.

Characterization of a potent antimicrobial lipopeptide via coarse-grained molecular dynamics.

The prevalence of antibiotic-resistant pathogens is a major medical concern, prompting increased interest in the development of novel antimicrobial compounds. One such set of naturally occurring compounds, known as antimicrobial peptides (AMPs), have broad-spectrum activity, but come with many limitations for clinical use. Recent work has resulted in a set of antimicrobial lipopeptides (AMLPs) with micromolar minimum inhibitory concentrations and excellent selectivity for bacterial membranes. To characterize a potent, synthetic lipopeptide, C16-KGGK, we used multi-microsecond coarse-grained simulations with the MARTINI forcefield, with a total simulation time of nearly 46µs. These simulations show rapid binding of C16-KGGK, which forms micelles in solution, to model bacterial lipid bilayers. Furthermore, upon binding to the surface of the bilayer, these lipopeptides alter the local lipid organization by recruiting negatively charged POPG lipids to the site of binding. It is likely that this drastic reorganization of the bilayer has major effects on bilayer dynamics and cellular processes that depend on specific bilayer compositions. By contrast, the simulations revealed no association between the lipopeptides and model mammalian bilayers. These simulations provide biophysical insights into lipopeptide selectivity and suggest a possible mechanism for antimicrobial action. This article is part of a Special Issue entitled: Membrane protein structure and function.

Blood-spinal cord barrier breakdown and pericyte reductions in amyotrophic lateral sclerosis.

The blood-brain barrier and blood-spinal cord barrier (BSCB) limit the entry of plasma components and erythrocytes into the central nervous system (CNS). Pericytes play a key role in maintaining blood-CNS barriers. The BSCB is damaged in patients with amyotrophic lateral sclerosis (ALS). Moreover, transgenic ALS rodents and pericyte-deficient mice develop BSCB disruption with erythrocyte extravasation preceding motor neuron dysfunction. Here, we studied whether BSCB disruption with erythrocyte extravasation and pericyte loss are present in human ALS. We show that 11 of 11 cervical cords from ALS patients, but 0 of 5 non-neurodegenerative disorders controls, possess perivascular deposits of erythrocyte-derived hemoglobin and hemosiderin typically 10-50 µm in diameter suggestive of erythrocyte extravasation. Immunostaining for CD235a, a specific marker for erythrocytes, confirmed sporadic erythrocyte extravasation in ALS, but not controls. Quantitative analysis revealed a 3.1-fold increase in perivascular hemoglobin deposits in ALS compared to controls showing hemoglobin confined within the vascular lumen, which correlated with 2.5-fold increase in hemosiderin deposits (r = 0.82, p < 0.01). Spinal cord parenchymal accumulation of plasma-derived immunoglobulin G, fibrin and thrombin was demonstrated in ALS, but not controls. Immunostaining for platelet-derived growth factor receptor-ß, a specific marker for CNS pericytes, indicated a 54 % (p < 0.01) reduction in pericyte number in ALS patients compared to controls. Pericyte reduction correlated negatively with the magnitude of BSCB damage as determined by hemoglobin abundance (r = -0.75, p < 0.01). Thus, the BSCB disruption with erythrocyte extravasation and pericyte reductions is present in ALS. Whether similar findings occur in motor cortex and affected brainstem motor nuclei remain to be seen.

Expanding the mutational spectrum of FHONDA syndrome.

AIM: The aim of the study is to present a rare case of Foveal Hypoplasia, Optic Nerve Decussation defects, and Anterior segment dysgenesis (FHONDA) confirmed by genetic testing with two separate pathogenic mutations in the SLC38A8 gene. MATERIALS AND METHODS: This was a case report. RESULTS: A 3-month-old female presented to a neuro-ophthalmology clinic with nystagmus. Her past medical and family history was unremarkable. Her examination demonstrated horizontal pendular nystagmus and small optic nerves with foveal hypoplasia bilaterally. Neuroimaging was unremarkable. She underwent an examination under anesthesia and electroretinogram (ERG). Her anterior segment examination was normal, and dilated fundus examination demonstrated foveal hypoplasia with diffuse pigment granularity. The ERG was normal. Genetic testing revealed two mutations in the SLC38A8 gene, p.Glu233Lys:c.697 G>A (pathogenic) and p.Asp283Ala:c.848A>C (likely pathogenic) with positive parental segregation analysis. Therefore, she was diagnosed with FHONDA. CONCLUSIONS: To our knowledge, this is the first report of a patient with FHONDA who is compound heterozygous for these two SLC38A8 mutations, which represents an expansion of the known mutational spectrum associated with this syndrome. Moreover, it may provide guidance into genetic counseling for patients and parents with these mutations.

Vitreous Hemorrhage in Pediatric Patients With X-Linked Retinoschisis: Characteristics and Outcomes.

OBJECTIVE: To report the management and outcomes of vitreous hemorrhage in pediatric patients with X-linked retinoschisis (XLRS). MATERIALS AND METHODS: Retrospective case series of pediatric patients with XLRS with vitreous hemorrhage between January 2000 and January 2022 at the Bascom Palmer Eye Institute. RESULTS: Nine patients (12 eyes) met inclusion criteria. The average age at presentation was 5.75 years and mean follow-up time was 6 years. All eyes (58.3%) that underwent fluorescein angiography exhibited peripheral capillary dropout. Six of 12 eyes (50%) were observed without intervention. Four of 12 eyes (33.3%) underwent intravitreal injection of bevacizumab and 2 (16.6%) underwent vitreoretinal surgery. Seven of 12 eyes (58.3%) had documented recurrence of vitreous hemorrhage during follow-up. All retinas were attached and had clear media at final follow-up. CONCLUSION: Fluorescein angiography is a helpful tool to evaluate the vascular phenotype in XLRS. Favorable anatomic outcomes were noted in this cohort, but recurrence of vitreous hemorrhage was common. [Ophthalmic Surg Lasers Imaging Retina 2023;54:513-518.].