DISRUPTION OF THE OUTER SEGMENTS OF THE PHOTORECEPTORS ON OPTICAL COHERENCE TOMOGRAPHY AS A FEATURE OF VITAMIN A DEFICIENCY.

PURPOSE: To describe the optical coherence tomography features of vitamin A deficiency. METHODS: Case series includes three male patients aged 50 to 66 years with vitamin A deficiency and visual symptoms ranging from 2 to 8 months. Examination included optical coherence tomography (OCT), fundus autofluorescence imaging, full-field electroretinography6 and laboratory work-up. RESULTS: Patient 1 had inoperable pancreatic neuroendocrine tumor and presented with worsening nyctalopia. The electroretinography showed absent rod function 2 months after the onset of symptoms, followed by a decrease of the cone function eight months after the onset. Optical coherence tomography showed poorly distinguishable outer segments of the photoreceptors with the disappearance of the interdigitation zone. At that time, vitamin A deficiency along with several other deficiencies was confirmed. After the initiation of parenteral nutrition, a substantial improvement of the patient's overall well-being was noted and the OCT showed normalization of the retinal structure. Two other patients were diagnosed with vitamin A deficiency based on similar OCT features. CONCLUSION: Disruption of the outer segments of the photoreceptors and the disappearance of the interdigitation zone on OCT may be helpful in recognition of vitamin A deficiency. Early detection and malnutrition evaluation are especially important in patients with a history of gastrointestinal disorders who may have several other underlying deficiencies. Treatment with either enteral or parenteral nutrition not only leads to resolution of visual symptoms but vastly improves their general condition and quality of life.

Stationary and Progressive Phenotypes Caused by the p.G90D Mutation in Rhodopsin Gene.

Mutations in rhodopsin gene (RHO) are a frequent cause of retinitis pigmentosa (RP) and less often, congenital stationary night blindness (CSNB). Mutation p.G90D has previously been associated with CSNB based on the examination of one family. This study screened 60 patients. Out of these 60 patients, 32 were affected and a full characterization was conducted in 15 patients. We described the clinical characteristics of these 15 patients (12 male, median age 42 years, range 8-71) from three families including visual field (Campus Goldmann), fundus autofluorescence (FAF), optical coherence tomography (OCT) and electrophysiology. Phenotypes were classified into four categories: CSNB (N = 3, 20%) sector RP (N = 3, 20%), pericentral RP (N = 1, 6.7%) and classic RP (N = 8, 53.3% (8/15)). The phenotypes were not associated with family, sex or age (Kruskal-Wallis, p > 0.05), however, cystoid macular edema (CME) was observed only in one family. Among the subjects reporting nyctalopia, 69% (22/32) were male. The clinical characteristics of the largest p.G90D cohort so far showed a large frequency of progressive retinal degeneration with 53.3% developing RP, contrary to the previous report.

Autologous neurosensory free-flap retinal transplantation for refractory chronic macular hole-outcomes evaluated by OCT, microperimetry, and multifocal electroretinography.

PURPOSE: To report the safety, anatomical and functional outcomes of autologous neurosensory retinal transplant in patients with a refractory large unclosed macular hole. PATIENTS AND METHODS: This is a prospective case series of four patients with large chronic macular hole that underwent vitrectomy and free-flap neurosensory retinal transplantation surgery with silicone oil tamponade. The hole was closed with an autologous retinal transplant of an approximate diameter of 1.5-1.8 mm, harvested outside the vascular arcades. Anatomical and functional outcomes were assessed using best-corrected visual acuity (BCVA-Snellen), optical coherence tomography (OCT), OCT angiography, microperimetry (MP), and multifocal electroretinography (mfERG). RESULTS: There were 2 male and 2 female patients with median age of 73 (60-81) years. The median follow-up period was 17 (13-23) months. The median preoperative size of the macular hole was 1872.5 (868-2591) µm at the widest basal diameter and 828 (556-1099) µm at the minimum diameter. Surgery resulted in the anatomical closure of the macular hole in all cases. The OCT showed structural integration of the transplant and reappearance of the inner segment ellipsoid to different extents. The BCVA improved from preoperative 0.1 (6/60; + 1.0 logMAR), 0.1 (6/60; + 1.0 logMAR), 0.05 (6/120; + 1.3 logMAR), and 0.005 (6/1200; + 2.3 logMAR) to 0.2 (6/30; + 0.7 logMAR) postoperatively in cases 1, 2, and 4, and to 0.1 (6/60; + 1.0 logMAR) in case 3. MP showed retinal function in the region corresponding to the area of the transplant (circle of 1.8 mm in diameter) in all patients after the surgery (median sensitivity in that region was 4.0 dB, range 1.8-12.4 dB). Improvement was noted in the patient that had MP performed before the surgery (mean sensitivity improved from 0 to 1.8 dB). Detectable function was mostly located in the peripheral regions of the transplant. Multifocal ERG showed abnormal function of the central ring and normal function of the second ring in 3 of 4 cases. The OCT angiography showed normal perfusion, without signs of neovascularization. There were no intra- or postoperative complications. CONCLUSION: Autologous retinal transplantation surgery is a successful technique for closing of large refractory macular holes. The procedure is safe and provides good anatomical results. Visual acuity, microperimetry, and mfERG suggest some gradual functional integration of outer regions of the transplants, but no central functional restitution has been detected as yet.

ISCEV extended protocol for the photopic On-Off ERG.

The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum procedure, but encourages more extensive testing. This ISCEV extended protocol describes an extension to the ERG standard, namely the photopic On-Off ERG, and outlines common clinical applications. A light stimulus duration of 150-200 ms is used in the presence of a rod-suppressing background to elicit cone-driven On- and Off-system ERG components. The On-response occurs after the stimulus onset and has a negative a-wave and positive b-wave. The Off d-wave is a positive component evoked by stimulus offset. Common diagnoses that may benefit from additional photopic On-Off ERG testing include retinal dystrophies and retinal disorders that cause dysfunction at a level that is post-phototransduction or post-receptoral. On-Off ERGs assess the relative involvement of On- and Off-systems and may be of use in the diagnosis of disorders such as complete and incomplete congenital stationary night blindness (complete and incomplete CSNB), melanoma-associated retinopathy, and some forms of autoimmune retinopathy. The photopic On-Off ERGs may also be useful in X-linked retinoschisis, Batten disease, Duchenne muscular dystrophy, spinocerebellar degeneration, quinine toxicity, and other retinal disorders.

ISCEV extended protocol for the photopic negative response (PhNR) of the full-field electroretinogram.

The International Society for Clinical Electrophysiology of Vision (ISCEV) Standard for full-field electroretinography (ERG) describes a minimum procedure, but encourages more extensive testing. This ISCEV extended protocol describes an extension to the ERG Standard, namely the photopic negative response (PhNR) of the light-adapted flash ERG, as a well-established technique that is broadly accepted by experts in the field. The PhNR is a slow negative-going wave after the b-wave that provides information about the function of retinal ganglion cells and their axons. The PhNR can be reduced in disorders that affect the innermost retina, including glaucoma and other forms of optic neuropathy. This document, based on existing literature, provides a protocol for recording and analyzing the PhNR in response to a brief flash. The protocol includes full-field stimulation, a frequency bandwidth of the recording in which the lower limit does not exceed 0.3 Hz, and a spectrally narrowband stimulus, specifically, a red flash on a rod saturating blue background. Suggested flash strengths cover a range up to and including the minimum required to elicit a maximum amplitude PhNR. This extended protocol for recording the PhNR provides a simple test of generalized retinal ganglion cell function that could be added to standard ERG testing.

Morphological and electrophysiological outcome in prospective intravitreal bevacizumab treatment of macular edema secondary to central retinal vein occlusion.

PURPOSE: To evaluate intravitreal bevacizumab (IVB) treatment in patients with central retinal vein occlusion (CRVO) by spectral domain optical coherence tomography (OCT) and electroretinography (ERG). METHODS: Twenty-two CRVO patients were treated with IVB injections and followed for 1 year. Morphological effect of treatment was observed with fluorescent angiography and OCT. Functional effect was followed with best corrected visual acuity (BCVA) and ERG: combined rod-cone response of the standard full-field ERG (dark adapted 3.0 ERG), photopic negative response (PhNR), and pattern ERG (PERG). RESULTS: Best corrected visual acuity (BCVA) improved by 18.2 letters after 6 months (p ≤ 0.001) and additional 4.7 letters by the 12th month (p ≤ 0.001). The central retinal thickness of 829.8 ± 256.7 µm decreased to 398.8 ± 230 µm (p ≤ 0.001) after 6 months and to 303.7 ± 128.9 µm during the following 6 months (p ≤ 0.001). The total macular volume (14.4 ± 4.2 mm(3)) decreased to 9.6 ± 3.2 mm(3) and 8.5 ± 2.0 mm(3) after 6 months and 1 year of treatment, respectively (p ≤ 0.001). Electrophysiological measures improved significantly after 6 months and 1 year of treatment: the a-wave implicit time of dark adapted 3.0 ERG from 25.6 ± 2.3 to 24.1 ± 2.1 and 24.1 ± 2.0 ms (p ≤ 0.01); the PhNR from -5.9 ± 6.6 to -9.4 ± 6.1 and -10.4 ± 4.6 µV (p ≤ 0.05); the PERG P50 amplitude from 0.2 ± 0.3 to 0.9 ± 0.6 and 1.1 ± 0.6 µV (p ≤ 0.001); and N95 amplitude from 0.4 ± 0.6 to 1.2 ± 0.9 and 1.6 ± 0.9 µV (p ≤ 0.001). CONCLUSIONS: Intravitreal bevacizumab (IVB) treatment of macular edema due to CRVO improved standard morphological measures and the electrophysiological function of outer and inner retinal layers, which was most evident in central retina.