A Simplified Model of Activation and Deactivation of Human Rod Phototransduction-An Electroretinographic Study.

Purpose: To test the hypothesis that a simple model having properties consistent with activation and deactivation in the rod approximates the whole time course of the photoresponse.

Methods: Routinely, an exponential of the form f = α·(1 - exp(-(τ·(t - teff)s-1))), with amplitude α, rate constant τ (often scaled by intensity), irreducible delay teff, and time exponent s-1, is fit to the early period of the flash electroretinogram. Notably, s (an integer) represents the three integrating stages in the rod amplification cascade (rhodopsin isomerization, transducin activation, and cGMP hydrolysis).

The Development of Retinal Function and Refractive Error in Children With Retinopathy of Prematurity.

Purpose: The purpose of this study was to test the hypothesis that retinopathy of prematurity (ROP) prolongs development of rod-mediated thresholds for detection of stimuli at 10 degrees but not 30 degrees eccentricity. In addition, to evaluate the thresholds at each site for an association with visual acuity (VA) and spherical equivalent (SE).

Methods: We estimated rod-mediated dark-adapted thresholds (DATs) for the detection of 2 degree diameter, 50 ms, blue (λ < 510 nm) flashes at 10 degrees and 30 degrees eccentric in former preterm subjects (n = 111), stratified by ROP severity: None (n = 32), Mild (n = 66), and Severe (n = 13).

Electroretinographic Responses in Retinopathy of Prematurity Treated Using Intravitreal Bevacizumab or Laser.

Purpose: Intravitreal injection of bevacizumab (IVB) offers advantages over laser photoablation for treatment of type 1 retinopathy of prematurity (ROP). However, retinal function has not, to date, been quantitatively compared following these interventions. Therefore, electroretinography (ERG) was used compare retinal function among eyes treated using IVB or laser, and control eyes.

The relation of the multifocal electroretinographic response to macular layer volume.

Purpose: To determine the association of the multifocal electroretinographic (mfERG) response amplitude with the volumes of the inner, postreceptor, and photoreceptor retinal layers in the region stimulated by each mfERG element.

Methods: Sixteen healthy, young adult control subjects were studied. Each of the 103 hexagonal elements of the standard, scaled mfERG were aligned, where possible, with patches of retina imaged using optical coherence tomography.

Dark-adapted threshold and electroretinogram for diagnosis of Usher syndrome.

Purpose: To determine the utility of ophthalmology evaluation, dark-adapted threshold, and full-field electroretinogram for early detection of Usher syndrome in young patients with bilateral sensorineural hearing loss.

Methods: We identified 39 patients with secure genetic diagnoses of Usher Syndrome. Visual acuity, spherical equivalent, fundus appearance, dark-adapted threshold, and full-field electroretinogram results were summarized and compared to those in a group of healthy controls with normal hearing.

The Fovea in Retinopathy of Prematurity.

Purpose: Because preterm birth and retinopathy of prematurity (ROP) are associated with poor visual acuity (VA) and altered foveal development, we evaluated relationships among the central retinal photoreceptors, postreceptor retinal neurons, overlying fovea, and VA in ROP.

Methods: We obtained optical coherence tomograms (OCTs) in preterm born subjects with no history of ROP (none; n = 61), ROP that resolved spontaneously without treatment (mild; n = 51), and ROP that required treatment by laser ablation of the avascular peripheral retina (severe; n = 22), as well as in term born control subjects (term; n = 111). We obtained foveal shape descriptors, measured central retinal layer thicknesses, and demarcated the anatomic parafovea using automated routines.

Retinal Function in X-Linked Juvenile Retinoschisis.

Purpose: To assess retinal function in young patients with X-linked juvenile retinoschisis (XLRS), a disorder that is known to alter ERG postreceptor retinal components and also possibly photoreceptor components.

Methods: ERG responses to full-field stimuli were recorded under scotopic and photopic conditions in 12 XLRS patients aged 1 to 15 (median 8) years. A- and b-wave amplitudes and implicit times were examined over a range of stimulus intensities.

Extracting the ON and OFF contributions to the full-field photopic flash electroretinogram using summed growth curves.

Under cone-mediated (photopic) conditions, an "instantaneous" flash of light, including both stimulus onset and offset, will simultaneously activate both "ON" and "OFF" bipolar cells, which either depolarize (ON) or hyperpolarize (OFF) in response and, respectively, produce positive-going and negative-going deflections in the electroretinogram (ERG). The stimulus-response (SR) relationship of the photopic ON response demonstrates logistic growth, like that manifested in the rod-mediated (scotopic) b-wave, which is driven by a single class of depolarizing bipolar cell. However, the photopic b-wave SR function is importantly shaped by OFF responses, leading to a "photopic hill.

Impact of Obstructive Sleep Apnea on Optic Nerve Function in Patients With Craniosynostosis and Recurrent Intracranial Hypertension.

Purpose: Assessment of combined impact of intracranial hypertension (ICH) and obstructive sleep apnea (OSA) on optic nerve function in children with craniosynostosis (CS).

Design: Retrospective cross-sectional study.

Methods: Patients treated at Boston Children's Hospital for CS who had an ophthalmic examination that included pattern reversal (pr)VEP (2013-2014) and history of ICH based on direct measurement, papilledema, or classic features on neuroimaging and during cranial vault expansion were included.

Microperimetry in Three Inherited Retinal Disorders.

Microperimetry (MP) is used to assess visual sensitivity mediated by the central retina. As such, MP performance is a candidate outcome measure for gene therapy trials. Herein, we review MP results in three inherited retinal disorders for which gene therapy trials have been initiated-choroideremia, Stargardt disease, and X-linked juvenile retinoschisis.

Retinal, visual, and refractive development in retinopathy of prematurity.

The pivotal role of the neurosensory retina in retinopathy of prematurity (ROP) disease processes has been amply demonstrated in rat models. We have hypothesized that analogous cellular processes are operative in human ROP and have evaluated these presumptions in a series on non-invasive investigations of the photoreceptor and post-receptor peripheral and central retina in infants and children. Key results are slowed kinetics of phototransduction and deficits in photoreceptor sensitivity that persist years after ROP has completely resolved based on clinical criteria.

Multifocal ERG Responses in Subjects With a History of Preterm Birth.

Purpose: The purpose of this study is to assess cone-mediated central retinal function in children with a history of preterm birth, including subjects with and without retinopathy of prematurity (ROP). The multifocal electroretinogram (mfERG) records activity of the postreceptor retinal circuitry.

Methods: mfERG responses were recorded to an array of 103 hexagonal elements that subtended 43° around a central fixation target.

Progressive retinal degeneration in a girl with Knobloch syndrome who presented with signs of ocular albinism.

Purpose: We report for the first time electroretinographic (ERG) evidence of progressive retinal abnormalities in a girl who presented in infancy with ocular features of albinism and gradually developed choroidal sclerosis and patchy retinal atrophy leading to a diagnosis of Knobloch syndrome (KS, OMIM 267750, COL18A1).

Methods: At age 2 months, nystagmus and esotropia prompted ophthalmic evaluation. The appearance of choroidal sclerosis and atrophic retinal patches led to further evaluation at age 8 years.

The neural retina in retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a neurovascular disease that affects prematurely born infants and is known to have significant long term effects on vision. We conducted the studies described herein not only to learn more about vision but also about the pathogenesis of ROP. The coincidence of ROP onset and rapid developmental elongation of the rod photoreceptor outer segments motivated us to consider the role of the rods in this disease.

Increment Threshold Functions in Retinopathy of Prematurity.

Purpose: To assess scotopic background adaptation in subjects with a history of preterm birth and retinopathy of prematurity (ROP). Retinopathy of prematurity is known to have long-term effects on rod photoreceptor and rod mediated postreceptor retinal function.

Methods: Rod-mediated thresholds for detection of 3° diameter, 50 ms stimuli presented 20° from fixation were measured using a spatial forced choice method in 36 subjects (aged 9-17 years) with a history of preterm birth and 11 age similar term-born subjects.

Extrafoveal Cone Packing in Eyes With a History of Retinopathy of Prematurity.

Purpose: To study the density and packing geometry of the extrafoveal cone photoreceptors in eyes with a history of retinopathy of prematurity (ROP). We used a multimodal combination of adaptive optics (AO) scanning light ophthalmoscopy (SLO) and optical coherence tomography (OCT).

Methods: Cones were identified in subjects (aged 14-26 years) with a history of ROP that was either severe and treated by laser ablation of avascular peripheral retina (TROP; n = 5) or mild and spontaneously resolved, untreated (UROP; n = 5), and in term-born controls (CT; n = 8).

Eye growth in term- and preterm-born eyes modeled from magnetic resonance images.

Purpose: We generated a model of eye growth and tested it against an eye known to develop abnormally, one with a history of retinopathy of prematurity (ROP).

Methods: We reviewed extant magnetic resonance images (MRIs) from term and preterm-born patients for suitable images (n = 129). We binned subjects for analysis based upon postmenstrual age at birth (in weeks) and ROP history ("Term" ≥ 37, "Premature" ≤ 32 with no ROP, "ROP" ≤ 32 with ROP).

Vigabatrin can enhance electroretinographic responses in pigmented and albino rats.

Purpose: To evaluate the effects of the antiepileptic medication vigabatrin (VGB) on the retina of pigmented rats.

Methods: Scotopic and photopic electroretinograms were recorded from dark- and light-adapted Long-Evans (pigmented) and Sprague Dawley (albino) rats administered, daily, 52-55 injections of 250 mg·kg(-1)·day(-1) VGB or 25-26 injections of 500 mg·kg(-1)·day(-1) VGB, or a corresponding number of sham injections. Sensitivity and saturated amplitude of the rod photoresponse (S, Rm(P3)) and postreceptor response (1/σ, Vm) were derived, as were sensitivity and amplitude of the cone-mediated postreceptor response (1/σ(cone), Vm(cone)).

Temporal summation in children with a history of retinopathy of prematurity.

Purpose: To assess temporal summation in children with a history of retinopathy of prematurity (ROP) by determining the critical duration (tCRIT) for complete temporal summation under rod-mediated conditions. From prior ERG studies, it is known that the kinetics of activation of phototransduction are prolonged in the ROP rod photoreceptor.

Methods: Dark-adapted thresholds for detecting 10° diameter stimuli with durations from 10 to 640 ms were measured.

Effect of retinopathy of prematurity on scotopic spatial summation.

Purpose: To evaluate scotopic retinal organization in retinopathy of prematurity (ROP) through a study of spatial summation.

Methods: Thresholds for a range of stimulus diameters (0.4°-10°) were measured using a two alternative, spatial, forced choice psychophysical procedure.

The rat with oxygen-induced retinopathy is myopic with low retinal dopamine.

Purpose: Dopamine (DA) is a neurotransmitter implicated both in modulating neural retinal signals and in eye growth. Therefore, it may participate in the pathogenesis of the most common clinical sequelae of retinopathy of prematurity (ROP), visual dysfunction and myopia. Paradoxically, in ROP myopia the eye is usually small.

Next-generation sequencing analysis of gene regulation in the rat model of retinopathy of prematurity.

Purpose: The purpose of this study was to identify the genes, biochemical signaling pathways, and biological themes involved in the pathogenesis of retinopathy of prematurity (ROP).

Methods: Next-generation sequencing (NGS) was performed on the RNA transcriptome of rats with the Penn et al. (Pediatr Res 36:724-731, 1994) oxygen-induced retinopathy model of ROP at the height of vascular abnormality, postnatal day (P) 19, and normalized to age-matched, room-air-reared littermate controls.

Photoreceptor and postreceptor responses in congenital stationary night blindness.

Purpose: To investigate photoreceptor and postreceptor retinal function in patients with congenital stationary night blindness (CSNB).

Methods: Forty-one patients with CSNB (ages 0.19-32 years) were studied.

Alterations of the tunica vasculosa lentis in the rat model of retinopathy of prematurity.

Purpose: To study the relationship between retinal and tunica vasculosa lentis (TVL) disease in retinopathy of prematurity (ROP). Although the clinical hallmark of ROP is abnormal retinal blood vessels, the vessels of the anterior segment, including the TVL, are also altered.

Methods: ROP was induced in Long-Evans pigmented and Sprague Dawley albino rats; room-air-reared (RAR) rats served as controls.