The influence of congenital corneal opacity on ERGs obtained using an abbreviated protocol.

BACKGROUND: Visual electrophysiology may be used to assess visual potential in infants with congenital corneal opacities (CCO). It is essential to recognize confounding effects from these opacities on the flash electroretinogram (ERG). METHODS: ERGs were recorded in awake children employing skin electrodes placed at the lower eyelid crease, both referred to a midfrontal electrode (Fz). A hand-held stimulator was used to present a mixed rod-cone and a dim white stimulus. Recordings were carried out before and after penetrating keratoplasty (PK), when performed. RESULTS: Five infants under the age of 12 months with visually significant CCO were evaluated. In all cases, initial ERGs employing the mixed rod-cone stimulus showed well-defined a-wave with reduced amplitude b-wave. Reduction of stimulus intensity resulted in an increase in the b-wave and normalization of the b:a ratio from 1.1 (range 0.7 to 1.3) to 2.8 (range 1.5 to 4.3). In three cases who underwent PK, the postoperative ERGs recorded with a mixed rod-cone stimulus were normal in waveform shape with a mean b:a ratio of 2.0 (range 1.7 to 3.0). CONCLUSION: Selective reduction of the scotopic bright flash ERG b-wave is typically caused by retinal dysfunction that is post-phototransduction or inner retinal. In infants with CCO, scotopic ERGs to bright flashes can show a reduced b:a ratio that improves or normalizes either after PK or stimulus intensity reduction. The study highlights that media opacity can contribute to the generation of an ERG with reduced b-wave in the absence of inner retinal dysfunction.

Melphalan toxicity following treatment of retinoblastoma identified by pattern electroretinogram.

PURPOSE: To describe a patient with retinoblastoma and subsequent maculopathy unrelated to the tumor but related to intra-arterial melphalan documented by pattern electroretinography. METHODS: Comprehensive ophthalmic evaluation, treatment with intra-arterial chemotherapy and subsequent follow-up including electroretinography to assess for macular dysfunction. RESULTS: A 3-year-old child was evaluated with electrophysiological investigations following treatment of unilateral Group D retinoblastoma with intra-arterial and intravitreal chemotherapy with melphalan. Pattern reversal visual evoked potential amplitude and P100 latency were normal in the left eye, but abnormal and delayed in the right eye. Pattern electroretinograms (pERGs) were abnormal on the right eye. Flash electroretinograms (fERGs) were normal on both eyes. Visual acuity dysfunction of 20/50 attributed to melphalan was seen on the right eye vs 20/40 on the left eye. CONCLUSION: Our case report demonstrates that pERG rather than fERG should be used to monitor baseline macular function and potential toxicity in children undergoing chemotherapy for retinoblastoma using skin electrodes when corneal electrodes are not tolerated.

Macular atrophy in JAG1-related Alagille syndrome: a case series.

BACKGROUND: : Alagille syndrome (AS) is a multisystem disorder associated with a range of ocular anomalies affecting the anterior and posterior segments. While chorioretinal abnormalities have been reported in Alagille Syndrome, identification of macular dystrophy and detailed clinical and electrophysiologic descriptions are scarce. MATERIALS AND METHODS: : A retrospective review was conducted to identify patients with a diagnosis of AS and retinal disease who were evaluated in the Division of Pediatric Ophthalmology, Strabismus, and Adult Motility at UPMC Children's Hospital of Pittsburgh. Criteria of AS included biopsy-proven bile duct hypoplasia, presence of major clinical features of AS, and molecular confirmation of the JAG1 gene. RESULTS: : This cohort included three patients, two females and one male, diagnosed with JAG1-Alagille syndrome. The diagnosis was made before 2 years of life in all patients. The mean follow-up period in our center was 8 years. All patients were found to have retinal pigmentary changes, macular atrophy, choroidal thinning, optic disc anomalies, and progressive decrease in vision. Marked retinal and macular dysfunction were found in electrophysiological studies. CONCLUSIONS: : Three patients with molecularly confirmed Alagille syndrome demonstrated unusual retinal and macular findings, with two showing progressive vision loss. Due to the rarity of retinal findings in AS and the observed progression of disease in our patients, clinical genetic testing for retinal dystrophies could be completed in two cases. These investigations failed to reveal a separate molecular cause for the observed retinal dystrophy, helping to confirm the association with JAG1-related AS.

A comparison of the Grass strobe and new LED photic stimulator for paediatric electroretinogram recordings.

PURPOSE: This study evaluated a new light-emitting diode (LED-S) photic stimulator and compared skin electroretinogram (ERG) responses obtained to those evoked by the Grass Instrument stimulator (GP-S). METHODS: Two sub-studies were combined to evaluate the difference in responses resulting from the LED-S and GP-S stimuli. The first was a photometry study that matched the LED-S stimuli to the GP-S. In the second study, electroretinograms (ERGs) were recorded under scotopic and photopic conditions using stimuli each stimulator. The stimuli were matched photometrically to measurements obtained from the photometer located 30 cm in front of the stimulators. In addition, the ERG responses were recorded from the LED stimulator when photometrically matched to the GP-S blue stimulus presented through a ganzfeld. The amplitudes and time peaks of the resulting ERG a- and b-waves were then measured and compared using paired T-tests. RESULTS: Study 1: The LED-S was matched to the GP-S at various intensity settings measured 30 cm away from the stimulator. Measurement through a ganzfeld full-field stimulator (GFFS) demonstrated that the GP-S had a significant hot spot centrally. Study 2: Photometrically matched ERGs evoked by both stimulators while employing the direct head-on measurements demonstrated multiple similarities. Similarities included component morphology, amplitude and implicit time across the two stimulators, excluding the rod-driven stimulus (GP-S setting employing a blue filter). Differences between the rod-driven ERGs evoked by the GP-S and LED-S while employing head-on photometric measurements were due to the significant difference in intensities between the two stimulators. The GP-S and LED-S evoked similar rod-driven ERG responses when they were matched using the GFFS photometrically matched intensities protocol. CONCLUSION: A hand-held stimulator is essential when recording ERG's in the practice of paediatric visual electrophysiology. The LED-S can match the GP-S stimulus intensities, making it a potential replacement for the GP-S. In addition, the LED-S has uniform intensity across the surface of the device compared to the GP-S, is silent for standard stimuli and can generate prolonged duration stimuli for the recording of on-off ERGs.

Ocular findings of albinism in DYRK1A-related intellectual disability syndrome.

BACKGROUND: Pathogenic variants in DYRK1A are associated with DYRK1A-related intellectual disability syndrome (DIDS). Common features of this diagnosis include microcephaly, intellectual disability, speech impairment, and distinct facial features. Reported ocular features include deep-set eyes, myopia, and strabismus. We present a case of DYRK1A-related intellectual disability syndrome with ocular findings of albinism and explore the possible pathogenesis of this previously unreported manifestation. MATERIALS AND METHODS: This is a single, retrospective case report of a child with DIDS who underwent an ophthalmic exam including detailed visual electrophysiology. Results: A 21-month-old female with microcephaly, failure to thrive, language delay, cleft palate, and cardiac defects had an ophthalmic exam showing myopia, strabismus, a hypopigmented fundus and crossed asymmetry on visual evoked potential (VEP), consistent with ocular findings of albinism. Whole exome sequencing identified a pathogenic DYRK1A variant; no albinism gene variants were reported. Her constellation of features is consistent with a diagnosis of DYRK1A-related intellectual disability syndrome; however, ocular features of albinism have not previously been reported in this condition. CONCLUSIONS: This is, to the best of our knowledge, the first report of ocular findings of albinism in a case of DYRK1A-related intellectual disability syndrome. We propose that ocular albinism is a novel ocular phenotype of DYRK1A-related disease. Ophthalmic exams in patients with this diagnosis should include thorough evaluation for ocular albinism, including VEPs.

Occipital Petalia and Albinism: A Study of Interhemispheric VEP Asymmetries in Albinism with No Nystagmus.

The purpose of this study was to assess chiasmal misrouting in a cohort of children with albinism with no nystagmus using hemifield visual evoked potentials (VEP) measures. METHODS: Monocular VEPs were recorded and analyzed from three electrodes (O1, Oz, and O2 referred to Fz) from 16 children with albinism without nystagmus. Pattern reversal (full field and hemifield stimulation), full field pattern appearance and flash stimuli were used to evoke VEPs for each eye. RESULTS: The amplitude of the pattern reversal VEPs to stimulation of the hemifield corresponding to the crossing pathways were as expected significantly larger than those to the non-crossing in each eye ((right eye p = 0.000004), (left eye p = 0.001)). Pattern reversal VEPs recorded from the left hemisphere were also larger than those from the right and most evident when comparing the crossing pathways of each eye (p = 0.004). CONCLUSIONS: This study has demonstrated electrophysiological differences in visual pathway function of the left and right hemisphere in subjects with albinism like that previously described in controls. Nasal field stimulation activated crossing and non-crossing pathways in patients with albinism and as a result, nasal hemifield VEPs in albinism are less lateralized compared to what is found in normal subjects.