[Multifocal electroretinography in the diagnosis and monitoring of early and intermediate stages of age-related macular degeneration]. / Mul'tifokal'naya elektroretinografiya v diagnostike i monitoringe rannei i promezhutochnoi stadii vozrastnoi makulyarnoi degeneratsii.

Multifocal electroretinography is a valuable diagnostic method for the objective localization and quantitative assessment of functional disorders of the central retina in age-related macular degeneration. It is used to detect early changes, monitor the course of the disease and treatment outcomes. In many cases, multifocal electroretinography is a more sensitive method for detecting functional disorders at the early/intermediate stage of age-related macular degeneration compared to morphological (optical coherence tomography) and subjective (visual acuity, perimetry) testing methods.

[Multimodal topographically oriented approach to the study of full-thickness macular holes]. / Mul'timodal'nyi topograficheski orientirovannyi podkhod k izucheniyu skvoznykh makulyarnykh razryvov.

PURPOSE: This article studies the relationship between structural changes according to the findings of optical coherence tomography (OCT) and OCT angiography (OCTA), microperimetry (MP), multifocal electroretinography (mfERG) parameters in topographically corresponding areas of the macular region in idiopathic full-thickness macular holes (FTMH). MATERIAL AND METHODS: OCT, OCTA, MP and mfERG were performed in 14 eyes with FTMH stages I-IV according to Gass. In 13 points at a distance of 0-2.5°, 2.5-5.0°, and 5.0-10.0° from the fixation point, the light sensitivity (LS), amplitude and latency of the P1 component were compared with the size of the hole, the area of cystic changes (CC) at the level of the inner nuclear layer (INL) and the outer plexiform layer and Henle fiber layer complex (OPL+HFL), vessel density in the superficial and deep capillary plexus (SCP and DCP). RESULTS: LS and P1 component amplitude were significantly reduced at a distance of up to 5.0° from the fixation point. LS correlates with the apical and basal diameter of the hole (R> -0.53), the area of CC in the INL (R> -0.62) and the OPL+HFL complex (R> -0.55), the density of vessels in the SCP at a distance of up to 2.5° from the fixation point (R>0.51) and in the DCP at a distance of up to 5° from the fixation point (R>0.49). The P1 amplitude correlates with the basal diameter of the hole (R= -0.38), the area of CC in the INL and the OPL+HFL complex (R> -0.33) and vessel density in the SCP (R=0.37) at a distance of up to 2.5° from the fixation point, as well as vessel density in the DCP at a distance of up to 5° from the fixation point (R=0.47). Vessel density in the DCP is significantly lower in the presence of CC in the retina (p<0.001). CONCLUSION: In FTMH, there is a relationship between bioelectrical activity and LS, and structural disorders, capillary perfusion in different layers of the retina. A multimodal topographically oriented approach allows studying the relationship between structural and functional parameters in individual points of the retina and can be used in monitoring of FTMH after surgical treatment.

Evaluation of Full-Field Stimulus Threshold Test Results in Retinitis Pigmentosa: Relationship with Full-Field Electroretinography, Multifocal Electroretinography, Optical Coherence Tomography, and Visual Field.

Objectives: The full-field stimulus threshold (FST) test was developed to evaluate the efficacy and safety of treatments of hereditary retinal diseases. In this study we performed the FST test in patients with retinitis pigmentosa (RP) and compared the results with findings from other ophthalmological tests. Materials and Methods: The study included 51 intermediate and advanced RP patients and 21 normal subjects. All patients and controls underwent routine examination and ophthalmological tests including visual field, optical coherence tomography, full-field and multifocal electroretinography (mfERG), and FST tests. During FST testing, the perception thresholds of retina to the white, blue, and red FST were determined in decibels. Results: The mean age of the patients and the controls were 35.2 and 33.5 years, respectively. For all RP patients, no response was obtained on full-field ERG. All subjects were able to perform reliable FST tests. The mean values of visual acuity and central macular thickness were significantly lower and visual field mean deviation values were significantly higher in the RP group than the controls. When we evaluated the mfERG findings, the mean P1 wave amplitudes in all rings were significantly lower and the mean peak times were significantly longer in RP patients than controls. In comparisons of FST test results, the mean values for white, blue, red and the difference between blue-red thresholds were significantly lower in the RP group than the control group. Conclusion: The FST test is a fast and a reliable exam which can be done in subjects with poor visual acuity and reduced visual field. The results of this study confirm that the FST test can measure retinal sensitivity in severely affected RP subjects with flat flash ERG.

New insights into amiodarone induced retinal and optic nerve toxicity: functional and structural changes.

Background: Amiodarone is widely used for heart arrhytmia. Previous studies have suggested the possibility of optic neuropathy with the chronic use of this drug. Objectives: To identify structural or functional changes in the retina and optic nerve in patients on chronic amiodarone therapy without visual complaints. Methods: This observational study included 15 eyes of 15 patients with cardiac arrythmia on chronic amiodarone treatment and 15 healthy matched subjects as a control group. All subjects underwent electrophysiological tests [pattern visual evoked potential (PVEP), pattern electroretinogram (PERG), multifocal electroretinogram (mfERG), and optical coherence tomography (OCT) and angiography (OCTA)]. Results: There were no statistically significant differences between the two groups regarding the PVEP, PERG, and the mfERG parameters. Macular and optic nerve head OCT and OCTA have not shown statistically significant differences except for the morphological parameters of the optic disc (p = 0.008 for the horizontal and p = 0.013 for vertical cup/disc ratio and p = 0.045 for rim area). Conclusion: Patients on chronic amiodarone therapy have not shown evident structural or functional changes in the retinal or optic nerve as demonstrated by electrophysiological tests, OCT, and OCTA results compared to controls.

Effects of Smoothing and Adaptive Filtering in Multifocal Electroretinography (mfERG).

(1) Background: mfERG testing is used to study the function of cone photoreceptors in the central retina. Various filters including "smoothing" (Smooth) and "adaptive data filtering" (Adapt) are used to simplify raw data. This study will seek to characterize the effect of data modification on raw patient data. (2) Methods: This was a retrospective study of patients with mfERG results at our institution. For each patient, raw mfERG data without filtering, with smooth level 4 modifier applied, and with adapt level 4 applied were collected and compared. (4) Conclusions: In all patients, smoothing and adaptive filter modifiers create statistically significant differences in both P1 latency and P1 amplitude values when compared to raw data. The impacts of these filters demonstrated in this study should impact physicians' decision making when interpreting mfERG results.

Functional and Morphological Characteristics of the Retina of Patients with Drusen-like Deposits and Systemic Lupus Erythematosus Treated with Hydroxychloroquine: A Retrospective Study.

PURPOSE: To evaluate the impact of drusen-like deposits (DLD) on retinal layer integrity and retinal function by optical coherence tomography (OCT) and multifocal electroretinography (mfERG) in patients with systemic lupus erythematosus (SLE). METHODS: We identified 66 eyes of 33 SLE patients treated with hydroxychloroquine (HCQ) that were categorized into two groups according to whether DLDs were present (34 eyes, Group One) or absent (32 eyes, Group Two). The groups were matched for age, sex, HCQ treatment duration, daily, and cumulative dosage. OCT (retinal layer thicknesses, central retinal thickness, CRT) and mfERG concentric ring analysis were analyzed and compared. RESULTS: CRT was significantly thicker in Group One compared to Group Two (273.21 ± 3.96 vs. 254.5 ± 7.62) (p = 0.023). Group One also demonstrated an overall thicker retinal pigment epithelium compared to Group Two; however, the other outer retinal layers, outer nuclear layer, and photoreceptor layer were found to be significantly thinner in Group One compared to Group Two. We found no differences in mfERG parameters between the two groups. CONCLUSIONS: DLDs in SLE patients lead to abnormal central retinal layer thickness, which has no measurable impact on cone-mediated retinal function assessed by mfERG.

[Multifocal analysis of the bioelectric potential and light sensitivity of the retina in thrombotic microangiopathy associated with malignant arterial hypertension]. / Mul'tifokal'nyi analiz elektricheskogo biopotentsiala i svetovoi chuvstvitel'nosti setchatki pri tromboticheskoi mikroangiopatii, assotsiirovannoi so zlokachestvennoi arterial'noi gipertenziei.

PURPOSE: This study evaluates the function of the retina according to multifocal electroretinography (mfERG) and its light sensitivity according to microperimetry (MP) in patients with thrombotic microangiopathy (TMA) associated with malignant hypertension (MH). MATERIAL AND METHODS: The study analyzed mfERG and MP data of 20 patients (40 eyes) aged 40.4±7.4 years (18 men, 2 women) with MH-associated TMA. In all patients TMA of the kidneys was verified by nephrobiopsy. The control group consisted of 20 healthy individuals (40 eyes) of the appropriate age. RESULTS AND DISCUSSION: A statistically significant decrease in the response density of P1 mfERG (nV/deg2) of the central retinal zone (0-27.7°) was found in study patients in comparison with the control group (p<0.05), differences in the latency of P1 mfERG (ms) were statistically insignificant (p>0.05). Analysis of MP data in study patients revealed a statistically significant decrease in the mean light sensitivity (dB) of the central field of vision (30°) (p<0.05) compared to the control group. A statistically significant correlation was found between the response density of P1 mfERG (nV/deg2) and mean light sensitivity (dB) in the corresponding quadrants of the visual field (p<0.05). A number of statistically significant correlations were found between the indicators of MP and mfERG and some non-ocular clinical manifestations of TMA in MH. CONCLUSION: A statistically significant decrease in the light sensitivity of the central field of vision caused by marked decrease in retinal function, probably of an ischemic nature, is characteristic for MH-associated TMA. In this disease the response density of P1 mfERG (nV/deg2) is a sensitive indicator of impaired retinal function. With the activation of systemic TMA, increase in blood pressure and deterioration of kidney function in MH, the light sensitivity of the eye also decreases.

Multifocal Electroretinography Changes over 12 Months after Resolution of Central Serous Chorioretinopathy: Prospective Observational Study.

INTRODUCTION: This prospective observational study aimed to evaluate the changes in retinal function after the anatomical resolution of central serous chorioretinopathy by multifocal electroretinography. METHODS: Thirty-two eyes of 32 patients with unilaterally resolved central serous chorioretinopathy were prospectively studied. Serial multifocal electroretinography examinations were performed at the initial visit for active central serous chorioretinopathy, the time of anatomical resolution (resolved central serous chorioretinopathy), and 3, 6, and 12 months after resolution. The peak amplitudes of the first kernel responses were analysed and compared with those in 27 age-matched normal controls. RESULTS: Compared with controls, the N1 amplitudes of rings 1-4 and P1 amplitudes of rings 1-3 showed statistically significant reductions at 12 months after the resolution of central serous chorioretinopathy (p < 0.05). The multifocal electroretinography amplitude substantially increased at the time of resolution and gradually improved until 3 months after the resolution of central serous chorioretinopathy. CONCLUSION: Serial examinations with multifocal electroretinography showed that retinal responses increased mostly after the resolution of central serous chorioretinopathy, and this improvement slowly progressed until 3 months; however, the multifocal electroretinography amplitudes remained statistically reduced 12 months after the anatomical resolution of central serous chorioretinopathy, indicating the residual functional deficits detected by multifocal electroretinography.

Multifocal electroretinography increases following experimental glaucoma in nonhuman primates with retinal ganglion cell axotomy.

PURPOSE: To determine whether short-latency changes in multifocal electroretinography (mfERG) observed in experimental glaucoma (EG) are secondary solely to retinal ganglion cell (RGC) loss or whether there is a separate contribution from elevated intraocular pressure (IOP). METHODS: Prior to operative procedures, a series of baseline mfERGs were recorded from six rhesus macaques using a 241-element unstretched stimulus. Animals then underwent hemiretinal endodiathermy axotomy (HEA) by placing burns along the inferior 180° of the optic nerve margin in the right eye (OD). mfERG recordings were obtained in each animal at regular intervals following for 3-4 months to allow stabilization of the HEA effects. Laser trabecular meshwork destruction (LTD) to elevate IOP was then performed; first-order kernel (K1) waveform root-mean-square (RMS) amplitudes for the short-latency segment of the mfERG wave (9-35 ms) were computed for two 7-hexagon groupings-the first located within the superior (non-axotomized) macula and the second within the inferior (axotomized) macula. Immunohistochemistry for glial fibrillary acidic protein (GFAP) was done. RESULTS: By 3 months post HEA, there was marked thinning of the inferior nerve fiber layer as measured by optical coherence tomography. Compared with baseline, no statistically significant changes in 9-35 ms K1 RMS amplitudes were evident in either the axotomized or non-axotomized portions of the macula. Following LTD, mean IOP in HEA eyes rose to 46 ± 9 compared with 20 ± 2 mmHg (SD) in the fellow control eyes. In the HEA + EG eyes, statistically significant increases in K1 RMS amplitude were present in both the axotomized inferior and non-axotomized superior portions of the OD retinas. No changes in K1 RMS amplitude were found in the fellow control eyes from baseline to HEA epoch, but there was a smaller increase from baseline to HEA + EG. Upregulation of GFAP in the Müller cells was evident in both non-axotomized and axotomized retina in eyes with elevated IOP. CONCLUSIONS: The RMS amplitudes of the short-latency mfERG K1 waveforms are not altered following axotomy but undergo marked increases following elevated IOP. This suggests that the increase in mfERG amplitude was not solely a result of RGC loss and may reflect photoreceptor and bipolar cell dysfunction and/or changes in Müller cells.

Evaluations of microvascular density by optical coherence tomography, angiography, and function by multifocal electroretinography of the macular area in eyes with branch retinal artery occlusion.

Introduction: It is reported that eyes with a branch retinal artery occlusion (BRAO) had normal full-field electroretinography (ERG) but the response of the multifocal electroretinography (mfERG) was reduced in the area of the arterial occlusion. Optical coherence tomography angiography (OCTA) is a recently appeared modality that can evaluate microvascularizations in different retinal layers and in different regions of the retina. The purpose of this study was to determine the density of the microcirculation and the function of the macular area of eyes with BRAO, and to determine whether they are significantly correlated. Methods: The OCTA and mfERG findings of 7 eyes of 6 patients (3 men, 3 women) were studied. The mean age of the patients was 71.7±10.6 years. The OCTA examinations were made with volume scans of 3 × 3 and 6 × 6 mm squares centered on the fovea. The macular vessel densities (mVD) in the superficial retinal layer (SRL) and deep retinal layer (DRL) were measured for the superior and inferior halves of 3  × 3  and 6  × 6 mm diameter concentric circles. The mfERGs were recorded with targets set to stimulate the focal areas of the retina corresponding to the areas examined by OCTA. Results: The OCTA examinations showed that the mVD of the 3 mm concentric circle in the SRL was significantly lower on the affected side than on the unaffected side (P = 0.022). No such difference was observed in the DRL. The N1 amplitude of the 20.2° concentric circle and the N1-P1 amplitude of the 10.1° concentric circle of the mfERGs were significantly smaller on the affected side than on the unaffected side (P = 0.047 and 0.031). A significant positive correlation was found between the mVD of the 6 mm concentric circle in the DRL and the P1-N2 amplitude of the 20.2° concentric circle (ρ = -0.929 and p = 0.003). Discussion: These findings indicate that OCTA images may be able to show changes in the density of the retinal macular microcirculation, and the mfERGs may be able to show alterations in the function of the macular area of the eyes with BRAO. A layer-by-layer analysis of the local retinal microcirculation and function should help in determining the pathogenesis of BRAO.

Electrophysiological and Visual Parameter Changes in Retinitis Pigmentosa Patients undergoing Autologous Platelet-Rich Plasma Therapy: A Randomized Control Trial.

Purpose: To assess the efficacy of autologous platelet-rich plasma (PRP) injections in suprachoroidal space and subtenon space in cases of retinitis pigmentosa, which is a genetic disease, leading to gradual loss of vision. Till date, no treatment is available. Methods: Seventy-eight eyes of 39 patients of retinitis pigmentosa having visual acuity ranging from reading of Early Treatment Diabetic Retinopathy Study (ETDRS) chart from 1 m onward to patients who were not able to read the ETDRS chart but whose visual acuity ranged from finger count close to face to <1 m were included in the study. The left and right eyes of each patient were randomized as the intervention eye and control eye. 0.2 mL of autologous PRP was injected in suprachoroidal space and 0.5 mL of PRP was injected in subtenon space of the intervention eye taking aseptic precautions. Injections were repeated at 15-day intervals up to 3 injections. Results: Majority of patients were in the age group of 18-30 years (20 cases) followed by 31-45 years (13 cases) and more than 45 years (6 cases). Intervention eyes showed a statistically significant improvement in visual acuity and multifocal electroretinography (mfERG). Improvement was noted in amplitude density latency and in ring ratio of mfERG. There was a significant improvement in best-corrected visual acuity (BCVA). However, no improvement in mfERG or BCVA was observed in the control group. Conclusions: Gene therapy may be the ultimate cure for retinitis pigmentosa, but it is unaffordable for many patients due to its high cost. PRP may be recognized as a modality to improve vision and stop further deterioration, especially in cases where functional vision is preserved. Negligible treatment costs and affordability will give power to economically disadvantaged patients.

[Multifocal electroretinography in assessment of the functional state of the central retina in patients with retinitis pigmentosa]. / Mul'tifokal'naya elektroretinografiya v otsenke funktsional'nogo sostoyaniya tsentral'noi zony setchatki pri pigmentnom retinite.

Retinitis pigmentosa (RP) is an inherited disease associated with various genetic mutations. Developments in the field of genetic engineering give relevance to the search for methods of studying retinal function, which can prove informative in the selection of patients for treatment. PURPOSE: To evaluate the information content of multifocal electroretinography (mfERG) in the diagnostics of the functional state of the central retina in retinitis pigmentosa (RP). MATERIAL AND METHODS: The study included 115 patients (228 eyes) with PR and 15 people (30 eyes) who comprised the control group. All subjects underwent standard ophthalmological examination, computer perimetry, color vision study, retinal spectral optical coherence tomography, ganzfeld electroretinography (gERG) and mfERG. The relationship between mfERG parameters and the degree of gERG changes, as well as various functional and morphological parameters of the retina was assessed. RESULTS: Visual acuity and perimetry indices varied over a wide range. GERG was unrecordable in 50.4% of cases. MfERG was registered in 214 (98.3%) eyes with varying degrees of change in visual acuity, visual field and gERG parameters. A medium degree positive relationship was revealed between the biopotential density of the retina in the foveal and parafoveal zones and visual acuity (rs=0.68; 0.63), a high degree - between the density of ttotal biopotential of the central retina (DValue) and the average light sensitivity (rs=0.9), a weak degree - between DValue and the thickness and volume of the peripheral retina (rs=0.37; 0.42), a medium negative correlation was found between the average defect in light sensitivity and the biopotential density in the periphery (Rings 4-5) on mfERG, DValue (rs= -0.67; -0.65; -0.69). CONCLUSION: MfERG detects retinal dysfunctions at an early stage of RP, in eyes with high visual acuity, normal parameters of the central visual field and gERG, as well as in low visual acuity, a pronounced decrease in light sensitivity, unrecordable gERG. MfERG can be informative in the selection of patients with RP for gene therapy.

Outcomes of transcorneal electrical stimulation therapy in the early stages of retinitis pigmentosa.

BACKGROUND: To investigate the effect of transcorneal electrical stimulation (TES) therapy in patients with retinitis pigmentosa (RP). METHODS: We performed TES therapy in 21 patients with RP in 12 sessions with 1-week intervals. The following parameters obtained before and after the TES therapy were compared statistically; the best corrected visual acuity (BCVA, logMAR), Ishihara color vision level, multifocal electroretinography (mf-ERG) response, automated visual field (VF) outcome, and the 25-item low vision quality-of-life (LVQOL) questionnaire points. RESULTS: The mean age of patients (6 females; 15 males) was 31.67 ± 9.80 years (20-50 years). While increases in BCVA level, color vision level, mf-ERG response in p1 amplitude of ring 1, and LVQOL questionnaire points were statistically significant, changes in VF test and other mf-ERG responses were not. Twenty of the patients (95.24%) stated that they were satisfied with the TES therapy. No considerable side effect was observed in any patient due to the therapy. DISCUSSION: The TES therapy may be an effective and safe treatment modality in slowing the RP progression, especially in the early stages of the disease. Longer-term follow-ups in larger patient populations are warranted.

Evaluation of Ring Amplitude and Factors Affecting Ring Amplitude in Multifocal Electroretinography in Diabetic Eyes.

PURPOSE: The aim of this paper was to evaluate the ring amplitudes in diabetic patients and to evaluate the effect of the risk factors for diabetic retinopathy on the ring amplitudes. We also aimed to investigate the success of ring amplitudes in classifying diabetic retinopathy. METHODS: The study included 32 eyes of 32 diabetic patients without retinopathy (DM), 34 eyes of 34 patients with mild non-proliferative diabetic retinopathy (NPDR) without macular edema, and 62 eyes of 62 age- and sex-matched controls (CG). All subjects were evaluated using mfERG. The relationship between age, diabetes duration, HbA1c and ring amplitudes and the effect of diabetes and hypertension on ring amplitudes were evaluated. Three-way ROC analysis was performed to evaluate the discrimination power of the ring amplitudes. RESULTS: In the comparison of the ring amplitudes, the amplitudes of the DM and NPDR groups were statistically significantly decreased compared to the CG (p < .05). A moderate to strong correlation was found between the duration of diabetes, HbA1c and ring amplitudes (p < .05). The effect of diabetes decreased towards the peripheral rings and hypertension did not affect ring amplitudes. Volume under the ROC surface of R1 = 0.65 had p < .05 and 95% CI [0.50-0.72], and the best cut-off point pair to differentiate the three classes was found to be c1 = 217.3, c2 = 151.2 in three-way ROC analysis. CONCLUSION: In conclusion, the effects of diabetes are unevenly distributed on the retina topographically. Diabetes affects the central rings more than peripheral rings in multifocal ERG. Both ring densities and ring ratios are effective ways to identify early changes in retinal function.

Ethambutol-induced optic neuropathy: Functional and structural changes in the retina and optic nerve.

BACKGROUD: Ethambutol hydrochloride (EMB) is used in the treatment of tuberculosis and is used as first line modality in combination with other medications. Ethambutol optic neuropathy (EON) is a rare but well-recognised adverse ocular event in patients who receive ethambutol for the treatment of mycobacterial infections and may be potentially devastating with reversible to irreversible changes in visual acuity. KEY FINDINGS: Optical coherence tomography has been used to evaluate the thickness of retinal nerve fibre and ganglion cell layers to look for degenerative changes and early markers. Electrophysiological tests like multifocal electroretinogram, visual evoked potentials and visual fields have been used to understand the functional changes associated with established EON and also whether these can be used to detect subclinical EON and correlate them with the structural changes. In this review, we have summarised evidence published till December 2021 related to evaluation of structural and functional changes in the retina and optic nerve in eyes with EON.

Evaluation of Corneal and Retinal Toxicity in Rheumatoid Arthritis Patients Treated with Hydroxychloroquine.

INTRODUCTION: The study aimed to assess the ocular toxicity of hydroxychloroquine (HCQ) by confocal microscopy, multifocal electroretinography (mfERG), and scanning laser polarimetry with variable corneal compensation (GDxVCC) in patients with rheumatoid arthritis (RA). METHODS: A cross-sectional, comparative case series study was retrospectively conducted on 61 patients under HCQ treatment for RA without fundoscopic anomalies (group 1), 65 RA patients with no HCQ treatment (group 2), and 27 normal subjects (group 3). A comprehensive ophthalmological examination, including confocal microscopy, mfERG, and GDxVCC, was performed in the three groups. RESULTS: In group 1, the duration of treatment ranged from 19 to 96 months (54.9 ± 15.2 months). The mean cumulative dose of HCQ was 446.1 ± 164.0 g (range 114-864 g). Confocal microscopy revealed hyper-reflective abnormal particles in 45 patients (73.8%) and beaded, tortuous fibers in 34 patients (55.7%) in group 1. No corneal change was observed in the other two groups. The mfERG responses in the 6 concentric rings (R1-R6) among the three groups differed except at R3 (all p < 0.05), and data from R1-R6 were not significantly different between groups 2 and 3. The retinal nerve fiber layer thicknesses were statistically thinner in group 1 than in groups 2 and 3 (all p < 0.05). CONCLUSIONS: Early signs of corneal and neural retina structure changes were detected in patients with RA treated with HCQ. Whether these findings should be a mark of drug recession still needs further study and more evidence.

Ocular Manifestations in a Chinese Pedigree of Familial Amyloidotic Polyneuropathy Carrying the Transthyretin Mutation c.401A>G (p.Tyr134Cys)

Familial amyloid polyneuropathy (FAP) caused by a genetic mutation in transthyretin (TTR) is an autosomal dominant hereditary disease. The retrospective, observational case series study presents the ocular clinicopathological findings of five cases carrying the TTR mutation c.401A>G (p.Tyr134Cys). Multimodal retinal imaging and electrophysiological examination, Congo red staining and immunohistochemical analysis of specimens, and genetic analyses were performed. Cases 1 and 2 were symptomatic with vitreous and retinal amyloid deposition and poor visual recovery. Case 3 had a symptomatic vitreous haze in the left eye with good postoperative visual recovery. The right eye of case 3 and the eyes of cases 4 and 5 were asymptomatic. Thicker retinal nerve fiber layer, retinal venous tortuosity with prolonged arteriovenous passage time on fluorescein angiography and retinal dysfunction detected by multifocal electroretinogram occurred even in asymptomatic eyes. Moreover, the internal limiting membrane from patients with FAP was stained positive for Congo red and transforming growth factor-ß1. The results highlight the amyloid deposition of mutant TTR in the optic disc and retina, even in the asymptomatic stage. The deposited amyloid leads to increased resistance to venous return and retinal functional abnormalities. Therefore, careful follow-up of structural and functional changes in the retina is needed, even in asymptomatic patients with FAP.

Neuroretinal dysfunction in patients affected by neurofibromatosis type 1.

AIM: To examine neuroretinal function by using the multifocal electroretinography (mfERG) test in patients with neurofibromatosis type 1 (NF1) without optic pathway gliomas (OPGs). METHODS: This study was conducted on 35 patients (35 eyes) with NF1 and 30 healthy subjects (30 eyes) for the control group. Each subject underwent a complete ophthalmological examination including spectral domain-optical coherence tomography (SD-OCT) and mfERG. The 1.5-Tesla magnetic resonance imaging (MRI) scan of the brain was performed in NF1 patients to assess the presence of OPGs. All participants were recruited having a best corrected visual acuity (BCVA) of no less than 20/20 in each eye. The amplitude and implicit time of the P1 wave (first-order Kernel component) were evaluated on mfERG. Data analysis was carried out in the two central degrees and in the four quadrants from two to 25 degrees of visual field. RESULTS: Statistically significant results were obtained for the P1 wave amplitudes in the 4 quadrants in NF1 patients compared to healthy controls, while the reduction was not significant in the 2 central degrees between the groups. A statistically significant difference was observed among the P1 wave amplitudes as recorded in the 4 quadrants within the NF1 group, with lower amplitudes detected in the nasal quadrants. No differences in the implicit times were recorded in the 2 central degrees and in the 4 quadrants as compared between NF1 patients and controls. CONCLUSION: Impaired neuroretinal function in NF1 patients is expressed in a decreased amplitude of the P1-wave between 2 and 25 central retinal degrees on mfERG. Altered intracellular signal transduction due to abnormal neurofibromin-mediated cyclic adenosine monophosphate (cAMP) generation, can be involved. The possible use of mfERG as subclinical retinal damage indicator has a potential utility in clinical practice for the follow-up of NF1 patients.

A novel phenotype associated with the R162W variant in the KCNJ13 gene.

BACKGROUND: Pathogenic variants in KCNJ13 have been associated with both autosomal dominant Snowflake vitreoretinal degeneration (SVD) and autosomal recessive Leber congenital amaurosis. SVD is characterized by aberrant vitreoretinal interface leading to increased risk of retinal detachment, crystalline retinal snowflake deposits, optic disc abnormalities, early-onset cataract, and cornea guttae. Reduced dark adaptation and reduced scotopic rod b-waves have also been described. We report a novel phenotype associated with the R162W variant in KCNJ13. METHODS: Four affected members of a Swedish family were included. Three of them were examined with best corrected visual acuity, Goldmann perimetry, full-field-and multifocal electroretinography, optical coherence tomography, fundus color photographs, fundus autofluorescence images, slit lamp inspection, and genetic testing. The fourth subject only managed genetic testing. RESULTS: All subjects carry the pathogenic missense variant; c.484C>T (NM_002242.4), R162W, in KCNJ13. ERG measurements revealed reduced macular-as well as general retinal function. Two of the subjects had a history of retinal detachment and the two younger subjects demonstrated early onset cataract. They all had structural macular changes and slightly gliotic optic discs. CONCLUSION: In this family, the R162W variant in KCNJ13, previously described in association with SVD, causes a somewhat novel phenotype including macular dystrophy and moderate reduction of general retinal function as the main features combined with disc abnormalities, retinal detachment, and presenile cataract that has been described before. In times of up-coming gene-based therapies, it is important to report new genotype-phenotype associations to improve the possibilities to identify future treatment candidates.

Electrophysiological evaluation and 18-month follow-up of two regimens with aflibercept for neovascular age-related macular degeneration.

PURPOSE: To compare two aflibercept treatment regimens and the electrophysiological outcome concerning cone and rod function in age-related macular degeneration (nAMD) over 18 months. METHODS: 41 patients with treatment-naïve nAMD were randomized 1:1 to either arm 1 or 2. Arm 1 received three consecutive monthly aflibercept injections, followed by bimonthly treatment until week 52. Thereafter, a treat-and-extend (TAE) regimen was applied. Arm 2 was treated according to a TAE protocol throughout the 18-month follow-up. We assessed visual acuity (VA), central retinal thickness (CRT), injection rate and interval, and evaluated cone and rod function with full-field and multifocal electroretinography (ffERG, mERG). RESULTS: There were no statistically significant differences in mean baseline VA, lesion type, age, gender, or symptom duration between the two arms. During the 18-month follow-up, mean VA improved in arm 1 (n = 19) from 63.5 ± 10.5 to 69.1 ± 9.2 letters; p = 0.098; and in arm 2 (n = 20) from 66.8 ± 13.6 to 73.9 ± 9.0 letters; p = .002. In both arms, mean CRT was significantly reduced; p < 0.000. At month 18, we found no significant difference in the number of injections or injection intervals between groups. Arm 1 had received 11.3 ± 1.7 injections vs. 10.9 ± 2.0 in arm 2. The mean injection interval was 9.2 ± 3.4 weeks vs. 9.5 ± 3.1, with 52% (n = 10) on the maximum 12-week interval in arm 1, and 50% (n = 10) in arm 2. The combined rod-cone a-wave amplitude significantly decreased over time; p = 0.043. The isolated rod b-wave amplitude showed a statistically significant decline; p = 0.026. The overall mERG amplitude and implicit time remained unchanged over time; p = 0.878 vs. p = 0.922. The central ring 1 mERG amplitude improved; p = 0.041, with an unaffected implicit time. CONCLUSIONS: After 18 months, both treatments arms have received a similar number of injections at comparable intervals. Electrophysiological evaluation shows no signs of toxicity concerning cone function. But ffERGs for the combined and isolated rod response have declined, possibly reflecting either toxic effects of the drug to rods or the natural course of the disease itself.