Efferent influences on the bioelectrical activity of the retina in primates.

PURPOSE: The existence of retinopetal (sometimes referred to as "efferent" or "centrifugal") axons in the mammalian optic nerve is a topic of long-standing debate. Opposition is fading as efferent innervation of the retina has now been widely documented in rodents and other animals. The existence and function of an efferent system in humans and non-human primates has not, though, been definitively established. Such a feedback pathway could have important functional, clinical, and experimental significance to the field of vision science and ophthalmology. METHODS: Following a comprehensive literature review (PubMed and Google Scholar, until July 2016), we present evidence regarding a system that can influence the bioelectrical activity of the retina in primates. RESULTS: Anatomical and physiological evidences are presented separately. Improvements in histological staining and the advent of retrograde nerve fiber tracers have allowed for more confidence in the identification of efferent optic nerve fibers, including back to their point of origin. CONCLUSION: Even with the accumulation of more modern anatomical and physiological evidence, some limitations and uncertainties about crucial details regarding the origins and role of a top-down, efferent system still exist. However, the summary of the evidence from earlier and more modern studies makes a compelling case in support of such a system in humans and non-human primates.

The effect of human gene therapy for RPE65-associated Leber's congenital amaurosis on visual function: a systematic review and meta-analysis.

BACKGROUND: RPE65-associated LCA (RPE65-LCA) is an inherited retinal degeneration caused by the mutations of RPE65 gene and gene therapy has been developed to be a promising treatment. This study aims to evaluate the association between changes in visual function and application of gene therapy in patients with RPE65-LCA. METHODS: Several databases (PubMed, Cochrane Library, and Web of Science) were searched for results of studies describing efficacy of gene therapy in patients with RPE65-LCA. Six studies, which included one randomized and five prospective non-randomized clinical trials, 164 eyes met our search criteria and were assessed. RESULTS: The BCVA significantly improved in treated eyes at 1 yr post treatment by - 0.10 logMAR (95% CI, - 0.17 - -0.04; p = 0·002), while there was no significant difference at 2-3 years post treatment (WMD: 0.01; 95% CI, - 0.00 - 0.02; p = 0·15). FST sensitivity to blue flashes also improved by 1.60 log (95% CI, 0.66-2.55; p = 0.0009), but no significant difference to red flashes (WMD: 0.86; 95% CI, - 0·29-2.01; p = 0.14) at 1 yr. There was no significant difference in central retinal thickness at 1 yr, but central retina in treated eyes appeared thinner at 2-3 years post treatment by 19.21 µm (95% CI, - 34.22 - -4.20; p = 0.01). CONCLUSIONS: Human gene therapy is a pioneering treatment option for RPE65-LCA. Although its efficacy appears to be limited to less than 2 yrs after treatment, it carries the potential for further improvement and prolongation of efficacy.

Intraocular Deposition of Copper and ERG Findings in a Patient With Progressive Vision Loss From Hypercupremia.

A 46-year-old woman who presented for progressive glare was found to have dense deposition of copper within Descemet's membrane and lens capsule in both eyes (OU). Systemic workup revealed elevated serum copper secondary to multiple myeloma. Following bilateral Descemet stripping automated endothelial keratoplasty and cataract extraction, a green discoloration of the vitreous was noted. The patient was followed for 3 years with serial exams and electroretinograms. Electroretinograms showed declining photopic response amplitude OU, indicative of progressive retinal toxicity from copper. Although retinal toxicity and vitreous copper deposition are common in chalcosis, this appears to be the first case of hypercupremia associated with these findings. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e324-e326.].

Cone and rod ERG phototransduction parameters in retinitis pigmentosa.

PURPOSE: To analyze cone and rod phototransduction parameters from ERG a-waves in patients with RP and to determine the relationships among these parameters, age, and mode of inheritance. METHODS: Sets of four white flashes (3.2-4.4 log scotopic troland [scot td-s]) were presented in the dark. The same stimuli were later presented against a rod-saturating background and the generated cone a-waves were subtracted from the dark-adapted responses to produce rod-only a-waves. The rod-only and cone a-waves were fit with computational models. RESULTS: Of 418 consecutive patients with retinitis pigmentosa (RP), cone a-waves were quantifiable in 136 (33%), whereas rod a-waves were quantifiable in 125 (30%). Cone R(max) (maximum response) and cone S (sensitivity) parameters were significantly below normal in all RP subgroups. Cone R(max) was lower in XlRP than in other forms of inheritance (P < 0.05). Cone S was abnormal in 77.9% of all patients with RP and in 96.8% of those with XlRP. More than 95% of the rod R(max) values were abnormal, whereas rod S was abnormal in 61.6% of these patients. CONCLUSIONS: The efficiency of cone phototransduction appears to be affected in all forms of RP, even in some patients in whom the sensitivity of rod phototransduction is normal. In this cross-sectional sample, there was no evidence that transduction efficiency decreased with increasing age of the patient. The X-linked mode of inheritance is associated with greater abnormalities in cone and rod photoreceptor function at a younger age compared with the other modes of inheritance.

Vitreous substitutes: a comprehensive review.

Vitreoretinal disorders constitute a significant portion of treatable ocular disease. Advances in vitreoretinal surgery have included the development and characterization of suitable substitutes for the vitreous. Air, balanced salt solutions, perfluorocarbons, expansile gases, and silicone oil serve integral roles in modern vitreoretinal surgery. Vitreous substitutes vary widely in their properties, serve different clinical functions, and present different shortcomings. Permanent vitreous replacement has been attempted with collagen, hyaluronic acid, hydroxypropylmethylcellulose, and natural hydrogel polymers. None, however, have proven to be clinically viable. A long-term vitreous substitute remains to be found, and recent research suggests promise in the area of synthetic polymers. Here we review the currently available vitreous substitutes, as well those in the experimental phase. We classify these compounds based on their functionality, composition, and properties. We also discuss the clinical use, advantages, and shortcomings of the various substitutes. In addition we define the ideal vitreous substitute and highlight the need for a permanent substitute with long-term viability and compatibility. Finally, we attempt to define the future role of biomaterials research and the various functions they may serve in the area of vitreous substitutes.

ERG findings in patients using hydroxychloroquine.

PURPOSE: To examine the electroretinographic findings derived by full-field electroretinography (ERG) and multifocal electroretinography (mfERG) in patients taking HCQ for different periods of time, including those without clinically visible evidence of toxicity. METHODS: The records for 26 consecutive patients (51 eyes, age 19-79) who had used HCQ for 1-30 years and who had an ERG and/or mfERG were reviewed. RESULTS: The patients fell into 5 groups, according to the results from their electrophysiological and clinical evaluation: no abnormalities (n = 13), cone b-wave delay (n = 2), decreased ERG amplitude (n = 6), borderline toxicity (n = 2) and toxicity (bull's-eye maculopathy; n = 3). Oscillatory potential (OP) amplitudes were decreased in many of the patients, even in the absence of any other clinical or ERG abnormality. MfERGs were normal in these patients without other abnormalities, but showed a bull's eye pattern of damage in a patient with clear toxicity. The full-field ERG parameters (including OPs) showed little relationship to the duration of HCQ usage or the cumulative dose. CONCLUSIONS: A substantial subgroup of patients showed varying degrees of diffuse ERG abnormality despite having no clinical signs (visual or fundus changes) of toxicity, and despite a range of cumulative doses. The mfERG showed toxicity, but its sensitivity in detecting early change remains to be determined. Further work is needed in order to separate pharmacological actions of the drug, retinopathy from the systemic disease, and potential toxic effects.

Senescence of human multifocal electroretinogram components: a localized approach.

BACKGROUND: Previous studies have shown significant age-related changes in the first-order kernel of multifocal ERG (mfERG) responses. All of these reports were based upon ring averages across the retinal field. This study was carried out to determine age-related changes in the localized response and localized variability in the mfERG parameters: N1P1 amplitude, scalar product and implicit time of P1. METHODS: MfERG recordings from 70 normal phakic subjects (ages 9-80 years) were analyzed with VERIS 4.8. Scalar product values (for each hexagon based on ring average templates) were obtained and analyzed for age-related changes. Statistical measures such as coefficient of variation (CV) and parameters of a linear regression model were applied. Point-by-point comparisons were made across hemifields. RESULTS: Each localized response showed a significant aging effect either in scalar product or in N1P1 amplitude. The average decline of the response was approximately 5% per decade, varying from 3.3% (peripherally) to 7.5% (perifoveally). The decline was significantly higher for the superior than for the inferior retina for amplitude parameters, corresponding to larger increases in P1 implicit time. The relative rate of change with age was similar for the nasal and the temporal retina. The average CV for all subjects at all locations was 29.4% (+/-4.1%). CONCLUSIONS: The localized approach revealed patterns of age-related change that were not apparent in the ring averages. Information about changes in discrete retinal areas with age should make the mfERG more useful in quantitatively monitoring progression of retinal disease.

Retinal evaluation after 810 nm Dioderm laser removal of eyelashes.

BACKGROUND: When operating hair removal lasers on the face or in the periorbital region, even with an ocular shield in place, patients often report seeing "flashing lights" each time the laser is fired. This phenomenon suggests stimulation of retinal photoreceptors and raises laser safety issues. OBJECTIVE: To perform retinal electrophysiologic studies to evaluate the safety of hair removal lasers in the periorbital region. METHODS: Five patients with severe trichiasis secondary to trachoma were studied. The 810 nm Dioderm laser (Cynosure, Inc., Chelmsford, MA) was used to treat the eyelash follicles on the lower eyelid of each patient. Cox III metal eye shields (Oculo-Plastik, Inc., Montreal, Canada) were placed behind the eyelids of both eyes during the laser procedure. Prior to irradiation, a comprehensive ophthalmic evaluation including pupillary and slit-lamp examination, funduscopy, and full-field electroretinograms (ERGs) was performed. A comprehensive ophthalmic evaluation including ERG testing was repeated 30 minutes and 3-6 months after completion of treatment. An independent blinded assessor evaluated the ERG studies. Subjective reports of laser light sensation, pain, and discomfort during and after the laser procedure were also assessed. RESULTS: There was no detectable change in slit-lamp, pupillary, or funduscopic evaluations after periorbital laser irradiation. Similarly the pre- and posttreatment ERGs were unchanged. Three patients reported seeing flashing lights during the procedure. CONCLUSION: We found no ERG evidence of retinal damage after laser hair removal in the periorbital region, with Cox III-type ocular shields over the eyes, even when patients subjectively reported "flashing lights" during laser irradiation.

Multifocal electroretinography evaluation for early detection of retinal dysfunction in patients taking hydroxychloroquine.

PURPOSE: To evaluate macular function using multifocal electroretinography (mfERG) in a cohort of asymptomatic patients taking hydroxychloroquine and a patient with maculopathy secondary to hydroxychloroquine treatment. METHODS: mfERG recordings were obtained for both eyes of 11 patients taking hydroxychloroquine without clinical signs of toxicity and 1 patient with toxic maculopathy. Initially, the classic m-sequence paradigm for the first-order kernel (103 hexagons; 2.7 candela x seconds/m2 peak luminance) was recorded. After that, another special stimulation mode was applied, which emphasized second-order adaptational effects (modulated multifocal flashes with interleaved global flashes, MF0F0 paradigm). RESULTS: The patient with toxic maculopathy and one patient without toxicity had multiple areas of decreased retinal responses bilaterally (classic m-sequence). The patient with toxicity and another three patients without toxicity presented with multiple areas of decreased retinal function in both eyes with the second-order component of the MF0F0 paradigm. Repeated recordings of 1 patient 8 months after the initial recording demonstrated evidence for reproducibility of the second-order adaptive effects. CONCLUSION: Clinically asymptomatic patients receiving hydroxychloroquine treatment can have substantial local decreases in their retinal function, as reflected by the changes in mfERG recordings, possibly indicating a preclinical stage of drug-related toxicity.