Central Cone Function Research Articles

Evaluation of Local Rod and Cone Function in Stargardt Disease.

PurposeIn this study, chromatic pupil campimetry (CPC) was used to map local functional degenerative changes of cones and rods in Stargardt disease (STGD1).Methods19 patients (age 36 ± 8 years; 12 males) with genetically confirmed ABCA4 mutations and a clinical diagnosis of STGD1 and 12 age-matched controls (age 37 ± 11 years; 2 males) underwent scotopic (rod-favoring) and photopic (cone-favoring) CPC. CPC evaluates the local retinal function in the central 30° visual field via analysis of the pupil constriction to local stimuli in a gaze-corrected manner.ResultsScotopic CPC revealed that the rod function of patients with STGD1 inside the 30° visual field was not impaired when compared with age-matched controls. However, a statistically significant faster pupil response onset time (∼ 40 ms) was observed in the measured area. Photopic CPC showed a significant reduction of the central cone function up to 6°, with a minor, non-significant reduction beyond this eccentricity. The time dynamic of the pupillary response in photopic CPC did not reveal differences between STGD1 and controls.ConclusionsThe functional analysis of the macular region in STGD1 disease indicates reduced central cone function, corresponding to photoreceptor degeneration. In contrast, the rod function in the central area was not affected. Nevertheless, some alteration of the time dynamics in the rod system was observed indicating a complex effect of cone degeneration on the functional performance of the rod system. Our results should be considered when interpreting safety and efficacy in interventional trials of STGD1.

Central Retina Functional Damage in Usher Syndrome Type 2: 22 Years of Focal Macular ERG Analysis in a Patient Population From Central and Southern Italy

Recent studies show that patients with Usher syndrome type 2 (USH2) have abnormal cone structure and density in the central retina. This occurs in the presence of normal acuity, opening the quest for additional sensitive functional measures of central cone function in USH. We tested here whether focal macular cone electroretinogram (fERG) could be such a tool. This retrospective study of central cone function loss was based on data from 47 patients with USH2 from the Ophthalmology Department of the Policlinico Gemelli/Catholic University in Rome. The analysis focused on the decrease of the fERG, obtained in response to a 41-Hz sinusoidal modulation of a uniform field presented to the central 18°, generated by red light-emitting diodes (LEDs) and superimposed on an equiluminant steady adapting background. fERG decrease was compared with the decrease of best-corrected visual acuity and Goldmann kinetic perimetry V4E field. fERG follow-up data document a severe and precocious loss of central cone function in USH2 patients, preceding losses in other measures of cone function. fERG is already reduced to 40% of control at the beginning of the second decade of life, and by 25 years of age, all USH2 patients have fERGs less than 30% of control values. fERG represents a sensitive tool to evaluate central cone function in USH2, anticipating the decline of other central cone function measures, such as visual acuity and Goldmann perimetry.

Long-Term Decline of Central Cone Function in Retinitis Pigmentosa Evaluated by Focal Electroretinogram

We evaluated long-term changes of central cone-mediated function in retinitis pigmentosa (RP) patients by recording focal electroretinograms (fERG).A cohort of 43 RP patients was followed from 4 to 16 years (average follow-up 9.3 years, average 10 examinations/patient) by recording the fERG response to a flickering uniform red field overlaying the central 18° of visual field (VF). Statistical censoring led to a reduced dataset of 32 patients (autosomal dominant 9, recessive 5, sporadic 5, x-linked 1, Usher II 12), from which long-term decay rates were estimated by global fitting of individual fERG amplitude time-curves.Long-term follow-up of central cone FERG amplitude showed two main features: short-term variability and long-term decline. fERG short-term variability range was 0.14 to 0.2 log units. Mean yearly decay rate of central fERG was 5.6% (95% confidence interval [CI] 4%-7%). Yearly decline depended on inheritance pattern, being significantly greater in autosomal recessive and sporadic compared to autosomal dominant RP. The degree of central cone fERG decline was unrelated to the size of the residual VF.The decline of central cone function is significantly slower than global cone function decline in RP. Central cone fERG loss is independent of residual VF.

Alteration of Rod and Cone Function in Children with Usher Syndrome

To evaluate the retinal function, with emphasis on phenotype and rate of progression, in infants and children with different genotypes of Usher syndrome. Fourteen children (2-10 years of age) with retinitis pigmentosa and hearing impairment were examined with full-field electroretinography (ERG) during general anesthesia, ophthalmologic examination, and genetic analysis. Five children were repeatedly examined (follow-up 5-10 years) with full-field ERG under local anesthesia and in 2 children multifocal ERG and optical coherence tomography (OCT) were performed. These results were compared to full-field ERG data from 58 children without retinal eye disorder. Six children were genotyped as Usher 1B, 2A, and 3A. Full-field ERG demonstrated early alterations corresponding to a rod-cone dystrophy in all children. A remaining rod function could be verified in the majority of the children up to 4 years of age. After 4 years of age, there was a further deterioration of the rod function; the progress was severe in Usher types 1 and 2 and moderate in Usher type 3. In all children, the cone function was moderately reduced, in a few cases almost normal. The results from the 58 children without retinal disorder confirm that full-field ERG during general anesthesia is reliable. Multifocal ERG confirmed a preserved central cone function and in OCT there were discrete structural alterations. Full-field ERG during general anesthesia in children with Usher syndrome demonstrates variable phenotypes and different degrees in rate of progression during childhood.

Retinal Disease in Usher Syndrome III Caused by Mutations in the Clarin-1 Gene

To determine the retinal phenotype of Usher syndrome type III (USH3A) caused by clarin-1 (CLRN1) gene mutations in a non-Finnish population. Patients with USH3A (n = 13; age range, 24-69) representing 11 different families were studied and the results compared with those from patients with USH2A (n = 24; age range, 17-66). The patients were evaluated by ocular examination, kinetic and static perimetry, near-infrared autofluorescence, and optical coherence tomography (OCT). Ten of 11 families had Ashkenazi Jewish origins and the N48K CLRN1 mutation. Rod function was lost in the peripheral field in the first two decades of life, but central rod function could be retained for another decade. Peripheral cone function was detectable into the third decade of life. Central cone function had a slower decline that extended for decades. Photoreceptor layer loss and features of retinal remodeling were present in retinal regions with severe visual dysfunction, even at the youngest ages tested. Central retinal structure could be normal in younger patients but structural integrity was lost in older patients. RPE disease generally paralleled photoreceptor degeneration. Comparisons between USH3A and USH2A suggested a common rod and cone phenotype but a more accelerated time course of rod loss in USH3A. USH3A and USH2A share patterns of rod and cone dysfunction and retinal structural abnormalities. Peripheral function measurements showed USH3A to be more rapidly progressive than USH2A.

RETINAL FUNCTION AFTER VITRECTOMY

To study retinal function after vitrectomy. Core vitrectomy was performed in 12 rabbits under standardized conditions using a vitreous cutting rate of either 600 or 1200 cuts/min. Full-field electroretinography (ERG) and multifocal electroretinography (mfERG) were performed pre- and postoperatively. Morphologic change was monitored by immunohistochemistry directed against glial fibrillary acidic protein (GFAP). Three days postoperatively, the b-wave amplitudes of all cone and rod responses of the ERG were significantly reduced in all vitrectomized eyes. At 28 days, the rod response was still reduced, but returned to normal by 58 days. No correlation was found between vitreous cutting speed and ERG findings. No reduction in the central cone function was detected in the mfERG. GFAP upregulation was found in the entire retina of vitrectomized eyes 3 days after surgery. GFAP expression was present after 28 and 58 days in eyes in which the vitreous cutting rate had been set to 600 cuts/min, but not in the 1200 cuts/min eyes. Pars plana vitrectomy transiently affects retinal function in rabbit eyes. Vitreous cutting speed is not related to the reduced function but appears inversely correlated to Müller cell activation, indicating that high-speed vitreous cutters are more lenient to the retina.

Multifocal ERG Reveals Several Patterns of Cone Degeneration in Retinitis Pigmentosa with Concentric Narrowing of the Visual Field

To analyze multifocal ERGs (mfERGs) in patients with retinitis pigmentosa (RP), with constricted visual fields and visual acuity satisfactory for steady fixation. The mfERGs of 86 eyes of 43 patients with various forms of inheritance and durations of RP were analyzed. A retinal scanning system with a 20-in. monitor was used to map central cone function. Electrical signals of the retina were detected by using DTL fiber electrodes. The site of the best response density of the mfERGs in the patients with RP was found in a central or eccentric position of the trace array. Depending on the position of the best response density in the two eyes, the patients were categorized into three groups. In the first group, the best response density was recorded from the central hexagon in both eyes, producing a central peak surrounded by very low responses in the three-dimensional presentation. In the second group of patients, the best responses were found to correspond to the central hexagon on only one side. In the fellow eye, however, the best response density appeared to be in an eccentric position. The patients in the third group did not present a central peak in the mfERG on either side. In scattered parts of the trace arrays, several acceptable responses were observed in all three groups that might represent patches of functioning retinal cone receptors. The results suggest highly variable central responses and groups of cones with preserved function in areas previously considered nonresponsive. The high variability of the central responses could be a result of variable foveal cone density, with differences in inheritance- and duration-related cone degeneration at the time of the examination. The authors stress the value of step-by-step analysis of the trace array of the mfERGs, which can reveal the still-functioning groups of cones.

ERGs, cone-isolating VEPs and analytical techniques in children with cone dysfunction syndromes.

Photoreceptor and post-receptoral function in children with congenital and acquired cone disorders was measured by full-field electroretinogram (ERG) and transient visual evoked potentials (VEPs). Subjects were five rod monochromats (RM), five with cone dystrophy (CD), and 30 controls. Patients were diagnosed by clinical findings, ERGs, and standard color vision tests. VEP stimuli were check reversals and color grating onsets that stimulated each photoreceptor type (L-, M-, or S-cones) or post-receptoral pathways (L-M, white/black). VEP signal-to-noise ratios (S/N) were calculated by Fourier analysis of VEP epochs. All RM patients showed extinguished cone ERGs. A near normal S-cone VEP was recorded from a blue-cone rod monochromat without any signal from the L- or M-cone stimuli. Two other RM patients were classified as incomplete RM based on a low-level VEP signal from either L- or M-cone stimuli. CD patients had mildly to severely reduced ERGs and VEPs were abnormal to all cone-isolating stimuli. The VEP S/N ratio was not significantly correlated with the amount of rod contrast in the color stimuli. Color VEPs provide an objective assessment of macular cone function in children with cone dysfunction syndromes that is more sensitive to residual central cone function than standard full-field ERGs. VEP techniques may be useful in the early detection of cone loss in children, especially in children who do not tolerate ERG testing.

Progressive Peripheral Cone Dysfunction

A 22-year-old man had a three-year history of progressive day blindness, most notably peripherally, and denied difficulty with central vision or color vision. Visual function studies demonstrated a diffuse dysfunction of the photopic system and normal scotopic function. The central cone function, however, was essentially normal. Visual acuity was 20/20 in each eye, results on AO-HRR and Ishihara color plate testing were normal, color naming visual fields demonstrated color discrimination in the central 10 degrees, and foveal adaptation was normal.