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Introduction: Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disorder classically characterized by central nervous system and renal abnormalities. Optic atrophy has been reported as a common ophthalmic feature, and other characteristics, including nystagmus, strabismus, oculomotor apraxia, and retinopathy have been reported; however, data on retinal involvement and dysfunction is limited. In this case report, we aim to describe retinal findings in a female adolescent diagnosed with GAMOS due to a homozygous variant in the WDR73 gene., Methods: A comprehensive ophthalmologic examination, including dilated fundus examination, fundus photography, electroretinogram (ERG), and optical coherence tomography (OCT), was performed. Systemic findings were obtained from medical records., Results: The patient's visual testing was significant for oculomotor apraxia, large angle esotropia, and cross fixation. On fundus examination, bilateral optic nerve pallor and retinal vessel attenuation were noted. OCT revealed bilateral retinal thinning. ERG demonstrated non-recordable rod and cone responses., Discussion: This case report describes multimodal imaging findings in a patient diagnosed with GAMOS due to biallelic homozygous variants in the WDR73 gene with comparison of retinal findings and ERG results to previously reported cases. Furthermore, we present OCT and fundus images for the first time in the literature.

Purpose: The purpose of this study was to report functional and anatomical outcomes of anti-VEGF treatment in eyes with autosomal recessive bestrophinopathy (ARB) presenting in the first decade of life., Methods: The study included case series of four eyes from two siblings with compound heterozygous mutations in the BEST1 gene who were treated with eight monthly intravitreal bevacizumab injections. Response to treatment was analyzed using color fundus photography, fundus autofluorescence, optical coherence tomography, OCT angiography, and microperimetry., Results: Patient 1 (male, age 9 years) had visual acuity of 20/20 in the right eye and 20/50 in the left eye. Patient 2 (female, age 10 years) had visual acuity of 20/25 in the right eye and 20/20 in the left eye. All eyes had multifocal subretinal deposition of lipofuscin and subretinal fluid, and three eyes had choroidal neovascularization (CNV). Lipofuscin material reabsorbed in 2 of 4 eyes, the CNV regressed in 3 of 3 eyes, a bacillary detachment resolved in 1 of 1 eye, but the subretinal fluid did not change. Functional improvement in visual acuity was noted, but MP showed scattered areas of reduced retinal sensitivity. No ocular or systemic side effects were detected., Conclusion: Anti-VEGF treatment of choroidal neovascularization in eyes with ARB resulted in anatomical changes that were only clinically significant in the eye with decreased visual acuity. The hyporeflective subretinal material remained unchanged suggesting a nonexudative cause. These findings provide new insights into the management of ARB, especially in pediatric subjects with CNV., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Mitochondria are critical modulators of antiviral tolerance through the release of mitochondrial RNA and DNA (mtDNA and mtRNA) fragments into the cytoplasm after infection, activating virus sensors and type-I interferon (IFN-I) response 1-4 . The relevance of these mechanisms for mitochondrial diseases remains understudied. Here we investigated mitochondrial recessive ataxia syndrome (MIRAS), which is caused by a common European founder mutation in DNA polymerase gamma (POLG1) 5 . Patients homozygous for the MIRAS variant p.W748S show exceptionally variable ages of onset and symptoms 5 , indicating that unknown modifying factors contribute to disease manifestation. We report that the mtDNA replicase POLG1 has a role in antiviral defence mechanisms to double-stranded DNA and positive-strand RNA virus infections (HSV-1, TBEV and SARS-CoV-2), and its p.W748S variant dampens innate immune responses. Our patient and knock-in mouse data show that p.W748S compromises mtDNA replisome stability, causing mtDNA depletion, aggravated by virus infection. Low mtDNA and mtRNA release into the cytoplasm and a slow IFN response in MIRAS offer viruses an early replicative advantage, leading to an augmented pro-inflammatory response, a subacute loss of GABAergic neurons and liver inflammation and necrosis. A population databank of around 300,000 Finnish individuals 6 demonstrates enrichment of immunodeficient traits in carriers of the POLG1 p.W748S mutation. Our evidence suggests that POLG1 defects compromise antiviral tolerance, triggering epilepsy and liver disease. The finding has important implications for the mitochondrial disease spectrum, including epilepsy, ataxia and parkinsonism., (© 2024. The Author(s).)

Purpose of Review: To discuss antisense oligonucleotide (ASON) therapy for autosomal dominant retinitis pigmentosa (adRP) caused by the proline-23-histidine (P23H) mutation in the rhodopsin gene., Recent Findings: Viral and nonviral therapies to treat adRP are currently under investigation. A promising therapeutic option is a nonviral approach using ASONs. This form of genetic therapy has demonstrated a dose-dependent and highly selective reduction of P23H mutant rhodopsin mRNA in animal models, and it is currently being investigated as a human phase 1/2 clinical trial., Summary: There are promising new therapies to treat adRP. ASON has shown encouraging results in animal models and has undergone a phase 1 clinical trial. ASON does not use a viral vector, is delivered with standard intravitreal injection, and its effects are reversible., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A significant portion of diabetic macular edema (DME) is refractory to anti-vascular endothelial growth factor (anti-VEGF) agents. This study investigates morphological and functional outcomes to a single intravitreal bevacizumab (IVB) injection in patients with center-involving DME (ciDME) at 4-6 weeks and compares treatment responders and non-responders based on spectral domain optical coherence tomography (SD-OCT) features., Methods: IRB approved observational, retrospective chart review of patients with ciDME, identified by ICD-10 code, who received IVB and underwent baseline and 4-6 weeks follow-up SD-OCT imaging between January 1, 2016 and January 19, 2021. Patients who had received previous treatment with anti-VEGF or intraocular steroids within 1 year were excluded. Variables included best-corrected visual acuity (BCVA), central subfield thickness (CST) and total macular volume (TMV). Eyes were classified as responders if CST reduction was greater than 10%. OCT scans were graded qualitatively by two masked graders using Imagivault software. Paired Student's t-tests, Wilcoxon signed rank tests and Chi-Square tests were used for analysis., Results: A total of 334 prospective subjects were identified, and after applying exclusion criteria 52 eyes from 46 patients (mean age 64.22 ± 8.12 years, 58.7% male) were included. Mean BCVA did not significantly change with treatment, 63.9 ETDRS letters (~ 20/50) at baseline and 65.9 ETDRS letters (~ 20/50) post-treatment (p = 0.07). Mean CST decreased from 466 ± 123 μm at baseline to 402 ± 86 μm post-treatment (p < 0.001). 22 (42.3%) of eyes were categorized as responders and 30 (57.7%) as non-responders. Average change in CST from baseline in responders was -164 μm (p < 0.001) and + 9 μm in non-responders (p = 0.47). Vitreomacular adhesion (VMA) was more prevalent in non-responders (28.7% vs. 4.8%, p = 0.03). In addition, cyst location in the inner nuclear layer (INL) was present more frequently in responders (95.5% vs. 73.3%, p = 0.037) as was subretinal fluid (45.5% vs. 13.3%, p = 0.01)., Conclusion: The short-term response to a single IVB was sub-optimal with structural but no functional improvements. Greater baseline CST, presence of INL cysts and subretinal fluid may represent factors indicative of a better treatment response., (© 2022. The Author(s).)

Background: Retinal measurements correlate with disease progression in patients with multiple sclerosis; however, whether they associate with neurologic disease in people with controlled HIV is unknown. Using spectral domain optical coherence tomography, we evaluated retinal differences between people with HIV and HIV-negative controls and investigated clinical correlates of retinal thinning., Methods: People with HIV on antiretroviral therapy for at least 1 year and HIV-negative controls recruited from the same communities underwent spectral domain optical coherence tomography, ophthalmic examination, brain MRI, and neuropsychological testing. Retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GC-IPL) thicknesses were compared between groups using analysis of covariance with relevant clinical variables as covariates. Linear regression was used to explore associations of HIV history variables, cognitive domain scores, and MRI volume measurements within the HIV group., Results: The HIV group (n = 69), with long-duration HIV infection (median time from diagnosis 19 years) and outstanding viral control have thinner retinal layers than HIV-negative controls (n = 28), after adjusting for covariates (GC-IPL: P = 0.002; RNFL: P = 0.024). The effect of HIV on GC-IPL thickness was stronger in women than in men (Women: P = 0.011; Men: P = 0.126). GC-IPL thickness is associated with information processing speed in the HIV group (P = 0.007, semipartial r = 0.309). No associations were found with retinal thinning and MRI volumes or HIV factors., Conclusions: People with HIV on antiretroviral therapy have thinning of the RNFL and GC-IPL of the retina, and women particularly are affected to a greater degree. This retinal thinning was associated with worse performance on tests of information processing speed., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In contrast to the classic autosomal recessive Wolfram syndrome, Wolfram-like syndrome (WLS) is an autosomal dominant disease caused by heterozygous variants in the WFS1 gene. Here, we present deep phenotyping of a mother and son with a WFS1 variant NM&#95;006005.3:c.2508 G > T, p. (Lys836Asn) detected with next-generation sequencing, which is novel at the nucleotide level. In this Greek family, the proband and mother had sensorineural hearing loss and mild non-progressive vision loss with optic nerve atrophy. An initial optic atrophy panel that did not test for WFS1 was unremarkable, but a broader inherited retinal dystrophy panel found the WFS1 variant., Conclusion: This study highlights the importance of including WFS1 sequencing in the evaluation of optic nerve atrophy to discover syndromic conditions.

Atypical Usher syndrome (USH) is poorly defined with a broad clinical spectrum. Here, we characterize the clinical phenotype of disease caused by variants in CEP78, CEP250, ARSG , and ABHD12 .Chart review evaluating demographic, clinical, imaging, and genetic findings of 19 patients from 18 families with a clinical diagnosis of retinal disease and confirmed disease-causing variants in CEP78, CEP250, ARSG , or ABHD12 . CEP78 -related disease included sensorineural hearing loss (SNHL) in 6/7 patients and demonstrated a broad phenotypic spectrum including: vascular attenuation, pallor of the optic disc, intraretinal pigment, retinal pigment epithelium mottling, areas of mid-peripheral hypo-autofluorescence, outer retinal atrophy, mild pigmentary changes in the macula, foveal hypo-autofluorescence, and granularity of the ellipsoid zone. Nonsense and frameshift variants in CEP250 showed mild retinal disease with progressive, non-congenital SNHL. ARSG variants resulted in a characteristic pericentral pattern of hypo-autofluorescence with one patient reporting non-congenital SNHL. ABHD12 -related disease showed rod-cone dystrophy with macular involvement, early and severe decreased best corrected visual acuity, and non-congenital SNHL ranging from unreported to severe.This study serves to expand the clinical phenotypes of atypical USH. Given the variable findings, atypical USH should be considered in patients with peripheral and macular retinal disease even without the typical RP phenotype especially when SNHL is noted. Additionally, genetic screening may be useful in patients who have clinical symptoms and retinal findings even in the absence of known SNHL given the variability of atypical USH.

Background : Atypical Usher syndrome has recently been associated with arylsulfatase G ( ARSG) variants. In these cases, characteristic findings include progressive sensorineural hearing loss (SNHL) without vestibular involvement and ring-shaped late-onset retinitis pigmentosa (RP). Materials and Methods: One patient with atypical Usher syndrome and a novel homozygous ARSG variant was included in this study. The patient underwent a comprehensive ophthalmic examination, including multimodal imaging and genetic testing. Results: A 60-year-old male of Persian decent presented to our clinic with a history of 20 years of progressive SNHL, and 10 years of progressive peripheral vision loss and pigmentary retinopathy. Consistent with previous reports of ARSG -related atypical Usher syndrome, fundus examination revealed ring-shaped retinal hyperpigmentation and fundus autofluorescence (FAF) demonstrated a six-zone pattern of autofluorescence. Optical coherence tomography (OCT) showed extensive cystoid spaces concentrated in the ganglion cell layer. Widefield OCT angiography at the level of the choriocapillaris showed signs of atrophy that corresponded to the FAF hypofluorescent zone. The patient was homozygous for a novel ARSG variant c. 1270 C > T, p. Arg424Cys. Conclusion: We report a novel ARSG variant in a case of atypical Usher syndrome and describe multimodal imaging findings that further characterize the effect of ARSG in the pathogenesis of atypical Usher syndrome.

Purpose: Autosomal recessive bestrophinopathy (ARB) and vitelliform macular dystrophy (VMD) are distinct phenotypes, typically inherited through recessive and dominant patterns, respectively. Recessively inherited VMD (arVMD) has been reported, suggesting that dominant and recessive BEST1-related retinopathies represent a single disease spectrum. This study compares adVMD, arVMD, and ARB to determine whether a continuum exists and to define clinical and genetic features to aid diagnosis and management., Methods: One arVMD patient and nine ARB patients underwent standard ophthalmic examination, imaging, electrophysiology, and genetic assessments. A meta-analysis of reported BEST1 variants was compiled, and clinical parameters were analyzed with regard to inheritance and phenotype., Results: Among 10 patients with biallelic BEST1 variants, three novel ARB variants (p.Asp118Ala, p.Leu224Gln, p.Val273del) were discovered. A patient with homozygous p.Glu35Lys was clinically unique, presenting with VMD, including hyperautofluorescence extending beyond the macula, peripheral punctate lesions, and shortened axial-length. A tritan-axis color vision deficit was seen in three of six (50%) of ARB patients. Attempts to distinguish recessively-inherited ARB and dominantly-inherited VMD genotypically, by variant frequency and residue location, did not yield significant differences. Literature meta-analysis with principle component analysis of clinical features demonstrated a spectrum of disease with arVMD falling between adVMD and ARB., Conclusions: This study suggests that arVMD is part of a continuum of autosomal recessive and dominant BEST1-related retinopathies. Detailed clinical and molecular assessments of this cohort and the literature are corroborated by unsupervised analysis, highlighting the overlapping heterogeneity among BEST1-associated clinical diagnoses. Tritan-axis color vision deficit is a previously unreported finding associated with ARB.

Purpose of Review: The aim of the present review is to provide a comprehensive summary of available knowledge regarding toxic maculopathy secondary to pentosan polysulfate sodium (PPS)., Recent Findings: PPS toxicity was described in 2018, and additional studies characterize it as dysfunction of the retinal pigment epithelium centered on the posterior pole, which can progress despite drug cessation. Requisite exposure can be as little as 0.325 kg and 2.25 years but averages closer to 1-2 kg and 10-15 years. Multimodal imaging should include near-infrared reflectance, optical coherence tomography, and fundus autofluorescence. Cross-sectional studies demonstrate evidence correlating cumulative dosing and the likelihood/severity of maculopathy. Early estimates of prevalence range from 12.7 to 41.7% depending on dosing, with overall rates around 20%., Summary: Reasonable evidence associates maculopathy with extended exposure to PPS, with an average reported incidence of around 20% in patients with long-term exposures. Patients with unexplained retinal pigment epithelium changes and difficulty with dark adaptation should be questioned regarding PPS exposure, and patients with known exposure to PPS should be examined. Further research is needed to refine screening protocols. Currently, providers should consider baseline examination and examination at 5 years and/or 500 g of exposure followed by yearly screening., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objective: To provide new insights into toxic maculopathy secondary to pentosan polysulfate (PPS) utilizing multimodal testing., Patients and Methods: Retrospective case-series of four patients from two academic centers evaluated with multimodal imaging, electrophysiology, dark adaptometry (DA), and genetic testing., Results: Median age was 58 years, exposure to PPS was 18.5 years, and cumulative dose of was 2,025 grams. Seven of eight eyes had visual acuity of 20/40 or better. Optical coherence tomography (OCT) angiography demonstrated increased choriocapillaris flow voids (54.25%) in cases compared to controls (13.2%). Two subjects had abnormal foveal avascular zone configurations. Two subjects demonstrated collapse of the retinal pigment epithelium nodular excrescences and progressive retinal thinning over 4 to 5 years on OCT. Electrophysiology was normal (3/3 patients), but DA was delayed (2/2 patients)., Conclusions: The authors describe novel findings of PPS maculopathy, including flow voids in the choriocapillaris. Progressive retinal thinning may suggest a secondary retinal effect. These findings may improve understanding of the pathophysiology. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:13-22.]., (© 2021 Abou-Jaoude, Davis, Fraser, et al.)

Purpose of Review: Gene therapy offers, for the first time, the possibility to cure diseases such as retinitis pigmentosa. The positive outcomes that led to the U.S. Food and Drug Administration (FDA) approval of Luxturna to treat Leber congenital amaurosis caused by RPE65 mutations created an optimistic atmosphere in the research, clinical and patient community. Despite this first success, we must understand that this is not a 'one treatment for all'. This review aims to explain the basic concepts of gene therapy and how they translate in different approaches that are utilized in ongoing clinical trials here reviewed., Recent Findings: In 2017, the FDA approved the first gene therapy treatment. In parallel, other approaches have gained attention. Different delivery methods (adeno-associated virus, lentivirus), injection sites (subretinal, intravitreal, suprachoroidal) and methodologies (gene replacement, silencing, editing) are currently being tested., Summary: Gene therapy is an evolving field in medicine and ophthalmology. Its success and application depends on several factors that are specific to the disease to treat. For now, we know it's a relatively safe approach and we look forward to the continued advancements of current ongoing clinical trials.

Objective: This study aims to determine the association between hyperglycemia, insulin therapy, and severe retinopathy of prematurity (ROP) in extremely low-birth-weight (ELBW) infants., Study Design: In this retrospective database study, we included all ELBW infants who were ≤ 32 weeks gestational age (GA). We excluded infants without any ophthalmology evaluation and infants who died before 28 days of life. A multivariable model was constructed to determine the association between hyperglycemia, insulin use, and severe ROP. We defined hyperglycemia as blood glucose (BG) > 180 mg/dL. Covariates were GA, small for GA status, discharge year, sex, Apgar score at 5 minutes, mechanical ventilation, oxygen use, bacteremia, and postnatal steroid exposure. We defined severe ROP as ROP requiring bevacizumab, cryotherapy, laser therapy, or vitrectomy. Sensitivity analysis using BG > 150 mg/dL and > 200 mg/dL was performed., Results: A total of 24,548 infants were included; 2,547 (10%) had severe ROP. Hyperglycemia alone was not associated with severe ROP (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.66-1.17). Hyperglycemia and insulin use were not associated with severe ROP (OR, 1.43; 95% CI, 0.91-2.23). BG > 150 mg/dL and insulin use were associated with severe ROP (OR, 1.34; 95% CI, 1.02-1.76)., Conclusions: Hyperglycemia alone was not associated with severe ROP in ELBW infants. However, we did observe a possible trend between the use of insulin and severe ROP., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Optical coherence tomography (OCT) has become an increasingly popular tool in various disciplines of medicine, particularly ophthalmology and neurology. It is an imaging technology that has revolutionized the practice of ophthalmology by providing anatomic detail of pathologic changes in the retina and optic nerve. OCT is routinely used as an ancillary test that can aid in the diagnosis and monitoring of neuro-ophthalmic diseases such as papilledema, optic neuritis, and neuroretinitis. OCT measurements have also been shown to predict visual prognosis in compressive optic neuropathies. Changes in OCT measurements have been used to study the course of particular neurologic diseases such as multiple sclerosis, suggesting that the data obtained may be useful as a biomarker in diagnosing and treating neurodegenerative disease. We present an up-to-date review of the OCT findings in several diseases of neurologic interest and provide clinical examples pertinent to the general neurologist.

Spectral domain coherence tomography (SD OCT) has become an important tool in the management of pediatric retinal diseases. It is a noncontact imaging device that provides detailed assessment of the microanatomy and pathology of the infant retina with a short acquisition time allowing office examination without the requirement of anesthesia. Our understanding of the development and maturation of the infant fovea has been enhanced by SD OCT allowing an in vivo assessment that correlates with histopathology. This has helped us understand the critical correlation of foveal development with visual potential in the first year of life and beyond. In this review, we summarize the recent literature on the clinical applications of SD OCT in studying the pathoanatomy of the infant macula, its ability to detect subclinical features, and its correlation with disease and vision. Retinopathy of prematurity and macular edema have been discussed in detail. The review also summarizes the current status of SD OCT in other infant retinal conditions, imaging the optic nerve, the choroid, and the retinal nerve fibre in infants and children, and suggests future areas of research.

Purpose: To evaluate effects of prematurity on early optic nerve (ON) development and the usefulness of ON parameters as indicators of central nervous system (CNS) development and pathology., Design: Prospective, cross-sectional, longitudinal study., Participants: Forty-four preterm infants undergoing retinopathy of prematurity (ROP) screening and 52 term infants., Methods: We analyzed ON from portable handheld spectral-domain optical coherence tomography (SD-OCT) images (Bioptigen, Inc, Research Triangle Park, NC) of 44 preterm and 52 term infants. The highest-quality ON scan from either eye was selected for quantitative analysis. Longitudinal analysis was performed at 31-36 weeks and 37-42 weeks postmenstrual age (PMA). Preterm ON parameters also were assessed for correlation with indicators of cognitive, language, and motor development and CNS pathology., Main Outcome Measures: Vertical cup diameter (vCD), vertical disc diameter (vDD), vertical cup-to-disc ratio (vCDR), cup depth, and indicators of neurocognitive development and CNS pathology., Results: At 37-42 weeks PMA, preterm infants had larger vCD and vCDR than term infants (908 vs. 700 μm [P<0.001] and 0.68 vs. 0.53 μm [P<0.001], respectively), whereas cup depth and vDD were not significantly different. Longitudinal changes (n = 26 preterm eyes; mean interval, 4.7 weeks) in vDD and in vCDR were an increase of 74 μm (P = 0.008) and decrease of 0.05 (P = 0.015), respectively. In preterm infants (n = 44), periventricular leukomalacia was associated with larger vCD (1084 vs. 828 μm; P = 0.005) and vCDR (0.85 vs. 0.63; P<0.001), posthemorrhagic hydrocephalus was associated with shallower cup (331 vs. 456 μm; P = 0.030), and clinical magnetic resonance imaging was associated with larger vCDR (0.73 vs. 0.64; P = 0.023). In 23 preterm infants with Bayley Scales of Infant Development scores, larger vCDR was associated with lower cognitive scores (P = 0.049)., Conclusions: This is the first analysis of ON parameters in premature infants using SD-OCT. It demonstrated that by age of term birth, vCD and vCDR are larger in preterm infants who were screened for ROP than in term infants. In this prospective pilot study, ON parameters in these preterm infants associate weakly with CNS pathology and future cognitive development. Future prospective studies with larger numbers are necessary before further conclusions can be made., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To study vascular features detected with spectral domain optical coherence tomography (SD-OCT) in subjects undergoing retinopathy of prematurity (ROP) screening., Design: Cross-sectional study., Participants and Controls: Fifty-seven premature neonates, 10 with plus disease in at least 1 eye and 47 without plus disease., Methods: Bedside noncontact SD-OCT imaging was performed after obtaining parental consent on 97 consecutive infants between January 2009 and September 2012. Fifty-seven subjects (31-49 weeks' post-menstrual age) who had an SD-OCT scan in at least 1 eye showing the edge of the optic nerve and at least 1 major retinal vascular arcade were included. One eye per subject was randomly selected for analysis. Two masked graders evaluated scans for (1) retinal vessel elevation, (2) scalloped retinal layers, (3) hyporeflective vessels, and (4) retinal spaces. To coalesce the weight of these features, a Vascular Abnormality Score by OCT (VASO) was created. For quantitative assessment of vessel elevation, retinal surface maps were created., Main Outcome Measures: Prevalence of SD-OCT vascular abnormalities, the VASO, intergrader agreement, and presence of elevation on surface maps., Results: From among 67 SD-OCT characteristics that were recorded, the most common characteristics found were vessel elevation (44%), hyporeflective vessels (40%), scalloped layers (22%), and retinal spaces (11%). Features significantly associated with plus disease were vessel elevation (P = 0.01), hyporeflective vessels (P = 0.04), and scalloped retinal layers (P = 0.006). Intragrader agreement was between 74% and 90% for all features. The VASO was significantly higher in subjects with plus disease (P = 0.0013). On 3-dimensional SD-OCT volumes, eyes with plus disease had greater retinal surface elevation that more often matched en face retinal vascular patterns., Conclusions: We present a novel 3-dimensional analysis of vascular and perivascular abnormalities identified in SD-OCT images of eyes with ROP. The SD-OCT characteristics that are more common in eyes with plus disease provide the first in vivo demonstration of the effects of vascular dilation and tortuosity on perivascular tissue. The VASO and surface maps also delineate the severity of vascular pathology in plus disease. Further studies evaluating these findings in eyes with pre-plus versus normal posterior pole vessels may determine the usefulness of SD-OCT in the early detection of vascular abnormalities in ROP., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To characterize optic nerve head (ONH) morphology and parameters, including vertical disk diameter, vertical cup diameter, and vertical cup/disk ratio in healthy, full-term newborns using a handheld spectral domain optical coherence tomography (SD-OCT) device., Methods: In this prospective observational case series, healthy white, black, and Hispanic full-term newborns delivered at the Duke Birthing Center between August 2010 and May 2011 underwent dilated fundus examination and SD-OCT imaging of the optic nerve in each eye. OCT parameters were calculated and compared for each group of infants., Results: A total of 58 consecutive newborns of white (n = 22), black (n = 15) and Hispanic (n = 21) ethnicity were included. Mean vertical disk diameter in white, black, and Hispanic newborns was 1.29 ± 0.15 mm (standard deviation), 1.38 ± 0.14 mm, and 1.38 ± 0.14 mm, respectively (white versus Hispanic, P = 0.02; white versus black, P = 0.07). Mean vertical cup diameter in white, black, and Hispanic newborns was 0.44 ± 0.15 mm, 0.56 ± 0.23 mm, and 0.46 ± 0.30 mm, respectively (white versus black, P = 0.03). Mean vertical cup/disk ratio was 0.34 ± 0.10 for white, 0.40 ± 0.17 for black, and 0.33 ± 0.20 for Hispanic newborns (P = 0.07 for white versus black)., Conclusions: Handheld SD-OCT is an effective means of imaging the ONH in newborns. Racial differences in cup/disk ratio are present at birth. These data may serve as the beginning of a normative dataset for characterizing development of the ONH as well as for comparison to the neonatal ONH in disease states., (Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.)

Background and Objective: To enhance understanding of ethnically diverse normal newborn retinal morphology, the authors report spectral-domain optical coherence tomography (SD-OCT) macular findings in healthy Hispanic newborns., Patients and Methods: In this IRB-approved prospective, observational case series, 20 full-term Hispanic newborns had dilated retinal examinations and imaging by hand-held SD-OCT without sedation at the Duke Birthing Center., Results: Of 20 newborns imaged (35% male; median gestational age: 39 weeks; range: 36 to 40 weeks), two (10%) had bilateral subfoveal fluid, including one case of bilateral double subretinal fluid pockets. Three eyes of two infants (10%) had retinal macular cystoid structures (one enlarged at 1.5 months, with resolution by 3 months). These SD-OCT findings were not visible by indirect ophthalmoscopy., Conclusion: Some Hispanic newborns have subretinal fluid or macular cystoid structures on SD-OCT. This study expands our understanding of findings seen by SD-OCT in healthy full-term newborns of various races.

Purpose: To determine whether choroidal imaging is feasible in preterm and term infants using an 840-nm portable spectral domain optical coherence tomography (SD-OCT) system without the use of enhanced-depth imaging techniques and to assess choroidal development by comparing choroidal thickness of preterm infants, term infants, and adults., Methods: SD-OCT images were obtained from 86 preterm infants, 59 term infants, and nine adults using a portable SD-OCT system plus nine adults using a tabletop system. An unprocessed image across the macula from one randomly selected eye of each participant was selected for determination of whether the choroidal-scleral junction (CSJ) could be visualized and for measurement of choroidal thickness., Results: Subfoveal CSJ was visualized in 96% of young-preterm infants (imaged from 30-36 weeks postmenstrual age [PMA]); 78% of term-aged preterm infants (imaged from 37-42 weeks PMA); 49% of term infants; and 39% of adult subjects. Racial pigmentation did not affect CSJ visibility in young-preterm infants (P = 0.57). Subfoveal choroidal thickness (SFCT) in young-preterm infants, term-aged preterm infants, term infants, and adults was 176 ± 53 μm, 289 ± 92 μm, 329 ± 66 μm, and 258 ± 66 μm, respectively, and these were all statistically significantly different from one another except term-aged preterms to adults., Conclusions: Infant choroid can be imaged with a portable SD-OCT system without enhanced depth imaging. Melanin in the RPE and choroid does not hinder outer choroidal imaging in young-preterm infants without advanced retinopathy of prematurity (ROP). In preterm infants, choroidal thickness increased with age but was thinner when compared to term infants suggesting delayed development due to ROP.

Retinopathy of Prematurity (ROP) is a leading cause of childhood blindness in the United States. Optical Coherence Tomography (OCT) is a relatively new imaging technology capable of imaging ocular structures in cross section at high resolution. We present an age-customized approach to perform Spectral Domain OCT in neonates and infants, and from SDOCT, the in-vivo development of the human fovea during the premature period up through term birth along with retinal changes unique to premature infants with ROP. Finally, we explore how this novel information may affect our understanding of ROP and the possible implications in vision and retinal development., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To report retinal findings for healthy newborn infants imaged with handheld spectral-domain optical coherence tomography (SD OCT)., Design: Prospective, observational case series., Methods: Thirty-nine full-term newborn infants underwent dilated retinal examinations by indirect ophthalmoscopy and retinal imaging by handheld SD OCT, without sedation, at the Duke Birthing Center., Results: Of the 39 infants imaged, 44% (17/39) were male. Race and ethnicity composition was 56% white, 38% black, 3% Asian, and 3% Hispanic. Median gestational age was 39 weeks (range, 36 to 41 weeks). Six (15%) of the 39 infants had bilateral subfoveal fluid on SD OCT not seen by indirect ophthalmoscopy. Eight infants (21%) had retinal hemorrhages noted on dilated retinal examination, 1 of which had subretinal fluid on SD OCT. Subretinal fluid was noted on follow-up examination to have resolved on SD OCT 1 to 4 months later. Infants with bilateral subretinal fluid had an older gestational age compared with infants without subretinal fluid (median, 40.4 vs 39.1 weeks, respectively; P = .03) and were more likely to have had mothers with diabetes (2/6 vs 0/33, respectively; P = .02). Vaginal versus Caesarian section delivery was not significantly different between the 2 groups., Conclusions: Some healthy full-term infants have bilateral subfoveal fluid not obvious on dilated retinal examination. This fluid resolves within several months. The visual significance of this finding is unknown, but clinicians should be aware that it is common when evaluating newborn infants for retinal pathologic features using SD OCT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To determine the dynamic morphologic development of the human fovea in vivo using portable spectral domain-optical coherence tomography (SD-OCT)., Design: Prospective, observational case series., Participants: Thirty-one prematurely born neonates, 9 children, and 9 adults., Methods: Sixty-two neonates were enrolled in this study. After examination for retinopathy of prematurity (ROP), SD-OCT imaging was performed at the bedside in nonsedated infants aged 31 to 41 weeks postmenstrual age (PMA) (= gestational age in weeks + chronologic age) and at outpatient follow-up ophthalmic examinations. Thirty-one neonates met eligibility criteria. Nine children and nine adults without ocular pathology served as control groups. Semiautomatic retinal layer segmentation was performed. Central foveal thickness, foveal to parafoveal (FP) ratio (central foveal thickness divided by thickness 1000 μm from the foveal center), and 3-dimensional thickness maps were analyzed., Main Outcome Measures: In vivo determination of foveal morphology, layer segmentation, analysis of subcellular changes, and spatiotemporal layer shifting., Results: In contrast with the adult fovea, several signs of immaturity were observed in the neonates: a shallow foveal pit, persistence of inner retinal layers (IRLs), and a thin photoreceptor layer (PRL) that was thinnest at the foveal center. Three-dimensional mapping showed displacement of retinal layers out of the foveal center as the fovea matured and the progressive formation of the inner/outer segment band in the opposite direction. The FP-IRL ratios decreased as IRL migrated before term and minimally after that, whereas FP-PRL ratios increased as PRL subcellular elements formed closer to term and into childhood. A surprising finding was the presence of cystoid macular edema in 58% of premature neonates that appeared to affect inner foveal maturation., Conclusions: This study provides the first view into the development of living cellular layers of the human retina and of subcellular specialization at the fovea in premature infant eyes using portable SD-OCT. Our work establishes a framework of the timeline of human foveal development, allowing us to identify unexpected retinal abnormalities that may provide new keys to disease activity and a method for mapping foveal structures from infancy to adulthood that may be integral in future studies of vision and visual cortex development., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare vitreoretinal pathology imaged with portable handheld spectral-domain optical coherence tomography (SD-OCT) to conventional indirect ophthalmoscopic examination in neonates undergoing screening for retinopathy of prematurity., Methods: Spectral-domain optical coherence tomography images were collected from 76 eyes of 38 neonates during 118 routine retinopathy of prematurity examinations. Imaging sessions in the Neonatal Intensive Care Unit were performed immediately after the subjects underwent a standard ophthalmic examination with indirect ophthalmoscopic by a pediatric ophthalmologist. Masked certified SD-OCT graders evaluated scans for preretinal and retinal findings including material in the vitreous, epiretinal membrane, intraretinal cystoid structures and deposits, optic nerve and vascular features, and severity and location of retinopathy of prematurity. The frequency of detection of these features by clinical examination and evaluation of SD-OCT images was compared to determine potential clinical advantages for each modality., Results: Portable SD-OCT imaging characterized macular features of retinal cystoid structures in 39% of examinations and epiretinal membrane in 32% of examinations. Neither feature was visualized by indirect ophthalmoscopy in any cases. The clinician using indirect ophthalmoscopy detected stage of retinopathy of prematurity and the presence or absence of Plus or pre-Plus disease. These were not visualized with SD-OCT., Conclusion: Spectral-domain optical coherence tomography provides new information about the premature infant retina that is of unknown importance relative to visual development and acuity. As used in this study, SD-OCT does not replace indirect ophthalmoscopy for evaluation of retinopathy of prematurity.

Optical coherence tomography (OCT) has transformed diagnostic ophthalmic imaging but until recently has been limited to the clinic setting. The development of spectral-domain OCT (SD-OCT), with its improved speed and resolution, along with the development of a handheld OCT scanner, enabled portable imaging of patients unable to sit in a conventional tabletop scanner. This handheld SD-OCT unit has proven useful in examinations under anesthesia and, more recently, in intraoperative imaging of preoperative and postoperative manipulations. Recently, several groups have pioneered the development of novel OCT modalities, such as microscope-mounted OCT systems. Although still immature, the development of these systems is directed toward real-time imaging of surgical maneuvers in the intraoperative setting. This article reviews intraoperative imaging of the posterior and anterior segment using the handheld SD-OCT and recent advances toward real-time microscope-mounted intrasurgical imaging., (Copyright 2011, SLACK Incorporated.)

We present a case of bilateral severe retinal edema with subretinal fluid in an infant diagnosed with neonatal hemochromatosis and liver failure. A macular cherry-red spot in each eye mimicked the clinical appearance of many metabolic storage diseases. Both the clinical retinal appearance and the anatomic abnormalities observed on spectral domain optical coherence tomography resolved after successful liver transplant., (Copyright © 2011 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.)

Purpose: To describe age-related considerations and methods to improve hand-held spectral domain optical coherence tomography (HH-SD OCT) imaging of eyes of neonates, infants, and children., Methods: Based on calculated optical parameters for neonatal and infant eyes, individualized SD OCT scan parameters were developed for improved imaging in pediatric eyes. Forty-two subjects from 31 weeks postmenstrual age to 1.5 years were imaged with a portable HH-SD OCT system. Images were analyzed for quality, field of scan, magnification, and potential clinical utility., Results: The axial length of the premature infant eye increases rapidly in a linear pattern during the neonatal period and slows progressively with age. Refractive error shifts from mild myopia in neonates to mild hyperopia in infants. These factors affect magnification and field of view of optical diagnostic tools applied to the infant eye. When SD OCT parameters were corrected based on age-related optical parameters, SD OCT image quality improved in young infants. The field of scan and ease of operation also improved, and the optic nerve, fovea, and posterior pole were successfully imaged in 74% and 87% of individual eye imaging sessions in the intensive care nursery and clinic, respectively. No adverse events were reported., Conclusions: SD OCT in young children and neonates should be customized for the unique optical parameters of the infant eye. This customization, not only improves image quality, but also allows control of the density of the optical sampling directed onto the retina.