Autologous Retinal Transplant for Macular Hole

We aim to review scientific literature concerning published studies on autologous retinal transplantation to treat macular hole patients. The following databases were searched: Medline and Medline Non-Indexed Items, Embase (1990–2020), Ovid Medline® (1990 to November 2020), Embase (1990 to November 2020), Ovid Medline® and Epub Ahead of Print, in-Process and Web of Science (all years). Search keywords included “autologous”, “retinal transplant”, “autologous neurosensory retinal free flap” “transplantation”, “macular hole”, and “macular hole surgery”. Eighteen case series and single case reports were reviewed. Preoperative and final best-corrected visual acuity, microperimetry and multifocal electroretinogram findings, macular hole closure rate, preoperative and postoperative ellipsoid zone, and external limiting membrane defects were obtained and analyzed. Indications of autologous retinal transplantation for macular hole surgery included refractory macular holes, conventional techniques, and large macular holes. The number of cases included in the different case series ranged from 2 to 130 cases, and prior macular hole surgeries of the patients ranged from 0 to 3. Overall, the published case series of autologous retinal transplants have reported a macular hole closure rate of 66.7 to 100%, as well as a significant improvement in best-corrected visual acuity. The most frequently reported complications included considerable intraoperative bleeding and postoperative dislocation of the graft. The presence of functionality in the graft area has also been documented by microperimetry and multifocal electroretinogram. In conclusion, the autologous retinal transplantation technique for macular hole patients has emerged as another surgical option, with a high macular hole closure rate and visual improvement.

Evaluation of Macular Function after Vitrectomy in Diabetic Macular Edema

Purpose: To document the effects of successful vitrectomy on retinal function and anatomy in diabetic patients. Methods: Three-port pars plana vitrectomy with detachment of posterior vitrous face was performed in 30 eyes of 25 patients with diabetic macular oedema DME (11 male, 14 Female).For each patients, visual acuity (VA) examination, measurement of retinal thickness using optical coherence tomography (OCT), full field electro-retinogram (ERG) and multifocal eletroretinogram (MF-ERG) were performed before and 1week,1month and 3months after vitrectomy. Results: Mean postoperative visual acuity was significantly improved (P<0.05); mean retinal thickness was significantly (P=0.001 ) decreased after 3monthes of surgery (from 450±150 into 220±50 micron ) .b-wave amplitudes of all cone and rod responses of ERG were significantly decreased in all vitrectomized eyes after 1 week. At one month, rod response was still unimproved but improved after 3months. Reduction in foveal Function as well as in para-foveal areas detected in the MF-ERG within 1st month. Then, mean P1 wave amplitude of MF-ERG of central ring increased and mean P1 wave implicit time decreased. These changes of MF-ERG parameters observed 3 months after vitrectomy. Conclusion: Multifocal electroretinogram can be useful to provide objective criteria for functional evaluation before and after vitrectomy in diabetic oedema.

Removing mains interference from the mfERG by applying a post-processing digital notch filter: for the good or the bad?

Purpose Ideally, the multifocal electroretinogram (mfERG) is recorded without noticeable intrusion of mains interference. However, sometimes contamination is difficult to avoid. A post-processing digital notch filter can help to recover the retinal response even in severe cases of mains interference. While a digital filter can be designed to have little to no impact on peak times, filtering out mains interference also removes the retinal signal content of the same frequency, which may result in a change of amplitude. The present study addressed this issue in the standard first order kernel mfERG. Methods In 24 recordings from routine exams with no perceivable mains interference, the effects of 50-Hz and 60-Hz non-causal digital notch filters on amplitude and peak time were assessed. Furthermore, the effect of filtering on contaminated traces was demonstrated and simulated mains interference was used to provide an example of nonlinear superposition of retinal signal and mains interference. Results mfERG amplitudes were reduced by 0%–15% (median 6%) with the 50-Hz filter and remained virtually unaffected with the 60-Hz filter. Simulations illustrate that spurious high-frequency components can occur in the filtered signal if a strongly contaminated signal is clipped due to a limited input range of the analog-to-digital converter. Conclusion The application of a 50-Hz digital notch filter to mfERG traces causes a mild amplitude reduction which will not normally affect the clinical interpretation of the data. The situation is even more favorable with a 60-Hz digital notch filter. Caution is necessary if the assumption of linear additivity of retinal signal and mains interference is violated.

Macular Morpho-Functional and Visual Pathways Functional Assessment in Patients with Spinocerebellar Type 1 Ataxia with or without Neurological Signs

Spinocerebellar ataxia type 1 (SCA-ATXN1) is an autosomal dominant, neurodegenerative disease, caused by CAG repeat expansion in the ataxin-1 gene (ATXN1). In isolated reports of patients with neurological signs [symptomatic patients (SP)], macular abnormalities have been described. However, no reports exist about macular anomalies in SCA1 subjects carrying the ATXN1 mutation without neurological signs [not symptomatic carriers (NSC)]. Therefore, the main aim of our work was to evaluate whether the macular functional and morphological abnormalities could be detectable in SP, genetically confirmed and with neurological signs, as well as in SCA-ATXN1-NSC, harboring pathogenic CAG expansion in ATXN1. In addition, we investigated whether the macular involvement could be associated or not to an impairment of RGCs and of their fibers and of the neural conduction along the visual pathways. Herein, nine SCA-ATXN1 subjects (6 SP and 3 NSC) underwent the following examinations: visual acuity and chromatic test assessments, fundus oculi (FO) examination, macular and peripapillary retinal nerve fiber layer thickness (RNFL-T) analysis by Spectral domain-Optical Coherence Tomography (Sd-OCT) acquisition, multifocal electroretinogram (mfERG), pattern reversal electroretinogram (PERG) and visual evoked potentials (VEP) recordings. In four eyes of two SP, visual acuity reduction and chromatic abnormalities were observed; in three of them FO changes associated with macular thinning and outer retinal defects were also detected. In three NSC eyes, slight FO abnormalities were associated with qualitative macular morphological changes. By contrast, abnormal mfERG responses (exclusively from foveal and parafoveal areas) were detected in all SP and NSC (18 eyes). No abnormalities of PERG values, RNFL-T, and VEP responses were found, but in one SP, presenting abnormal papillo-macular bundle neural conduction. Results from our SCA-ATXN1 cohort suggest that a macular dysfunction, detectable by mfERG recordings, may occur in the overt disorder, and unexpectedly in the stage of the disease in which there is still an absence of neurological signs. In NSC, an exclusive dysfunction of preganglionic macular elements can be observed, and this is associated with both normal RGCs function and neural conduction along the visual pathways.

A novel 5-ring multifocal electroretinography stimulus for detecting hydroxychloroquine retinal toxicity

Purpose Multifocal electroretinogram (mfERG) shows great utility as a screening tool to detect early hydroxychloroquine (HCQ) retinopathy, but its widespread use is limited by the lack of accessibility and long test duration. In this study, we evaluated a novel concentric 5-ring mfERG stimulus to provide a simplified and rapid protocol for screening HCQ toxicity. Methods Patients referred for HCQ retinopathy screening were consented to this observational cross-sectional study. Patients with amblyopia, high refractive error (more than 8 diopters), other retinal diseases precluding appropriate evaluation or history of retinal surgery were excluded. The data were collected from patients undergoing HCQ screening at a single center from July 2019 to March 2020. Patients were tested with the new concentric 5-ring mfERG stimulus, standard 61-hexagon mfERG stimulus, spectral domain optical coherence tomography and automated 10-2 visual fields. For the main outcome, the 5-ring mfERG was compared to 61-hexagon stimulus to determine the time-to-test completion and assess the association between ring (R1–R5) amplitude and ring ratio compared against cumulative dose, dose by real body weight and duration of therapy using Pearson correlation. Results In total, 52 patients (104 eyes; 5 males and 47 females) were recruited with a mean age of 59 years (range 23–85 years). The 5-ring protocol was markedly quicker to perform (1.3 ± 0.2 min; mean (SD)) compared to the 61-hexagon protocol (5.2 ± 0.6 min), p < 0.0001; n = 10 patients. The new R2/R5 ring ratio showed a moderate correlation with daily dose (r = − 0.640), cumulative dose (r = − 0.581) and duration of therapy (r = − 0.417). Similar correlations were observed with the new R2/R4 ring ratio which were not significantly different from the new R2/R5 correlation coefficients. The new R2/R5 ring ratio demonstrated a stronger correlation with daily (p = 0.002) and cumulative dose (p = 0.0001) compared to the 61-hexagon stimulus. Conclusions In this exploratory study, our novel 5-ring mfERG protocol significantly shortened data acquisition time while providing comparable results to the standard 61-hexagon stimulus for detecting HCQ-induced electrophysiological changes that are correlated with HCQ dosages and treatment duration. Our protocol has the potential to be more clinically practical by simplifying routine screening.

Effect of Axial Length on Full-Field and Multifocal Electroretinogram

Background The Electroretinogram is a mass potential, which reflects the summed electrical activity of the retina. Full-field ERG measures the electrical signals from the whole retina in response to a light stimulus. The weakness of the full-field ERG is that it cannot provide topographical information regarding the functional integrity of the retina and cannot detect subtle functional defects. The response is dominated by the peripheral retina due to its predominance of retinal cells. Aim of the Work to investigate the effect of axial length on fullfield (ffERG)and multifocal ERG (mfERG). Subjects and Methods Forty-four eyes of 44 healthy subjects were included in this case series study which has been conducted at Ain shams university hospitals after the approval of the research ethical committee in the faculty of medicine, Ain Shams University between July 2018 and September 2019. Full ophthalmologic examination was performed for all participants, including visual acuity assessment (Best corrected visual acuity) using Snellen chart, calculation of spherical equivalent (SE), slit Lamp biomicroscopy examination with IOP measurement via Goldmann applanation tonometry (GAT), and fundus examination by indirect ophthalmoscope or via 90 D VOLK lens to assess macular area. Axial length measurement, ffERG & mf-ERG. Results; We found that in the absence of fundus changes, mfERG parameters showed decreased amplitudes with increase in axial length. The Six- Rings Response Densities showed negative correlation with AL while there is no significant correlation between Six- Rings Response Densities and SE. The Six- Rings P1 Amplitude showed negative correlation with AL while there is no significant correlation between P1 Amplitude and SE. The Six- Rings N1 Amplitude showed negative correlation with AL while there is no significant correlation between P1 Amplitude and SE. The four- quadrant Response Densities showed negative correlation with AL while there is no significant correlation between four- quadrant Response Densities and SE. The four- quadrant P1 Amplitude showed negative correlation with AL while there is no significant correlation between P1 Amplitude and SE. The four- quadrant N1 Amplitude showed negative correlation with AL while there is no significant correlation between P1 Amplitude and SE. There is no significant correlation between full-field clinical ERG parameters and both AL and SE. Conclusion In the absence of fundus changes, mfERG parameters showed decreased amplitudes with increase in axial length. For correct interpretation of ERG responses in clinical practice, we recommend consideration of axial length measurement when evaluating mfERG responses.

Ocular Toxoplasmosis Associated with Unilateral Pigmentary Retinopathy That May Mimic Retinitis Pigmentosa: Diagnostic Dilemmas

We report a unique case of coexisting pigmentary retinopathy and ocular toxoplasmosis in a young male patient. A 23-year-old man presented with sudden visual deterioration in the left eye (LE). The fundus findings revealed bone spicule-shaped pigment deposits, a slightly pale optic disc, arteriole constriction, cystoid macular edema with an epiretinal membrane, and two small inflammatory chorioretinal scars in the right eye, with a concentric narrowing of the visual field and a nonrecordable multifocal electroretinogram (ERG). An active inflammatory lesion at the border of a pre-existing chorioretinal scar in the macula was found in the LE, with a central scotoma in the visual field. Moreover, the patient tested positive for anti-Toxoplasma gondii immunoglobulin G antibodies and showed positive results in polymerase chain reaction testing of aqueous humor. Fluorescein angiography revealed hyperfluorescence in the early phase with fluorescein leakage. A multifocal ERG of the LE showed selective loss of responses from the central 10 degrees. Genetic testing revealed heterozygosity in the RP1 and CELSR1 genes. Our case illustrates challenges in the diagnosis of unilateral pigmentary retinopathy. Based on the typical toxoplasmic lesions in the LE and two scars likely caused by inflammation, our patient was diagnosed with pigmentary retinopathy probably related to toxoplasmosis. Genetic consultation did not confirm the diagnosis of retinitis pigmentosa, but more advanced tests might be needed to definitively exclude it.

Relationship between structural and functional changes in glaucomatous eyes: a multifocal electroretinogram study

Background The nasal to temporal amplitudes ratio (N/T) of multifocal electroretinography (mfERG) scans measured within 5° of the macula can be used to detect glaucomatous change. The photopic negative response (PhNR) of mfERG elicited by a circular stimulus centered on the fovea was significantly reduced in eyes with glaucoma. The PhNR to B-wave ratio (PhNR/B) is the optimal measure of the PhNR. However, clinical superiority for evaluating glaucoma patients has not been determined between N/T and PhNR/B yet. Methods For morphological assessments, ganglion cell complex (GCC) in six regions and the average were measured by optical coherence tomography (OCT). For functional assessment, Humphrey visual fields (VF) with mean sensitivities (MT) and mfERG scans with parameters of N/T and the multifocal photopic negative response to B-wave ratio (mfPhNR/B) were measured. Sixty-nine eyes of 44 glaucoma patients were included and correlations between mfERG parameters and OCT or VF parameters were evaluated. Results The mean age of patients was 59.4 years. The mean deviation for all eyes obtained with the VF 30–2 and VF 10–2 was − 7.00 and − 6.31 dB, respectively. Significant correlations between GCC thickness or VF parameter and the N/T were found, especially in the inferior and inforotemporal retinal areas corresponding to superior and superonasal VF sectors (GCC vs N/T; coefficient = − 7.916 and − 7.857, and MT vs N/T; coefficient = − 4.302 and − 4.437, in the inferior and inforotemporal retinal areas, respectively, all p values < 0.05). However, similar associations were not obtained between mfPhNR/B and OCT or VF parameters. The mfPhNR/B only in the inferotemporal sector was significantly correlated with the average thickness of GCC (coefficient = 4.823, P = 0.012). Conclusions The N/T was correlated with GCC and VF in more numbers of measurement areas than the mfPhNR/B in the current study, however, a future study modifying the stimuli and amplitudes to obtain the spatial correspondence to OCT and VF measurement will be required to evaluate the value of mfERG.