Multifocal Electroretinography Research Articles

Effect of spatial averaging on the amplitude ring ratio in multifocal electroretinography.

The purpose of this study was to evaluate the effect of spatial averaging on the multifocal electroretinography (mfERG) amplitude ring ratios used in screening for hydroxychloroquine (HCQ) toxicity. This was a retrospective review of the records of patients screened for HCQ retinopathy at the USF Eye Institute (University of South Florida) during the period of 2015-2020. Patients were tested binocularly with Diagnosys mfERG system (Diagnosys LLC, Lowell, MA). Only the records of patients referred internally were used. The effects of the lowest level (level 1, or 8%) of spatial averaging on the P1 amplitude ring ratios used for screening of HCQ maculopathy: R1/R2, R2/R5, R5/R3 and R5/R4, were evaluated. The records of 40 patients (4 males, 36 females) aged 54.4 ± 14.1 years were selected for analysis. The use of spatial averaging had a significant effect on P1 amplitudes, and on the ring ratios and this effect was correlated with the magnitude of the amplitudes and the ratios. Spatial averaging diminished P1 amplitude significantly in ring 1 (p < 0.0001) and increased it slightly in ring 4 (p < 0.05), while it had no effect on the amplitude of the other three rings. Although as a group spatial averaging had a moderate effect on the R1/R2 ratio (~ -15%), on an individual basis the range was wide, from -36 to 43%. The effect on the other ring ratios was similar: The average group effect was ~ -5%, ~ -3.4% and ~ -4% for R2/R5, R5/R3 and R5/R4 ratios, but individual effects ranged from 0.18% to -27.3%, 0.9% to -14.2% and 0.9% to -26.2%, respectively. For all ring ratios used in this analysis, spatial averaging has a substantial effect on the ring ratio, which could affect the interpretation of the results. Therefore, use of spatial averaging should be avoided when analyzing mfERG results for HCQ screening.

Retinal structure-function correlation in type 2 diabetes.

To examine the relationship of visual function as assessed by visual acuity, contrast sensitivity, and multifocal electroretinography (mfERG) to macular structural and microvascular measures on optical coherence tomography (OCT) and angiography (OCTA) in individuals with diabetes. This is a prospective observational study conducted at a tertiary eye care centre in India. Right eyes of 121 adults with type 2 diabetes with no diabetic retinopathy (DR), mild or moderate nonproliferative DR (NPDR) were examined. Severe NPDR, proliferative DR and diabetic macular oedema were excluded. Participants underwent assessment of glycated haemoglobin (HbA1C), blood pressure, best corrected visual acuity (LogMAR), contrast sensitivity (CS), mfERG, ultrawide field fundus photography, OCT and OCTA. Correlations were assessed by Spearman's rank correlation (rho). Of the total of 121 eyes, 89 had No DR, 32 had mild to moderate NPDR. In the No DR group, the LogMAR acuity was significantly and negatively correlated to central subfoveal thickness (CST) (rho = -0.420), macular vessel density (rho = -0.270) and perfusion (rho = -0.270). (ii) Contrast sensitivity correlated to foveal avascular zone circularity (rho = 0.297); (iii) mfERG P1 response densities were better with higher macular perfusion index (rho = 0.240). In the NPDR group, the LogMAR acuity also showed a significant negative correlation to CST (rho = -0.379). Other correlations were not significant. Retinal and visual functional changes are evident in diabetic patients with No DR and are correlated to subclinical retinal structural changes detectable using multimodal imaging.

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

BackgroundThe 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.MethodsFor 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.ResultsThe 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).ConclusionsThe 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.

Multifocal electroretinography in amblyopia

Cortical pathology has been incriminated as the major site of involvement in amblyopia. The purpose of this study was to identify whether there were functional abnormalities in the retina of amblyopic eyes using multifocal electroretinography (mfERG).

Does ganciclovir exert retinal toxicity after multiple continuous intravitreal injections?

BackgroundThe objective of this study is to report a case of acute retinal necrosis in which abnormalities in visual function did not correspond to retinal anatomical outcomes.Case presentationA 39-year-old female diagnosed with acute retinal necrosis underwent repeated (nine rounds) intravitreal ganciclovir injection (3 mg/0.1 ml) into the left eye, one injection every 2 weeks. During the therapy, the patient noticed her visual acuity declining gradually. The best corrected visual acuity in the left eye was 20/33. The visual field showed massive visual damage. There was no posterior necrotizing involvement, no macular edema or exudation, and only slight abnormity of the interdigitation zone in the fovea area was visible on OCT. Angio-OCT revealed normal capillary density of three retinal capillary and choriocapillaris layers. The visually evoked potential was normal. The photopic single-flash response showed a declined amplitude of a-wave and b-wave. The amplitudes of photopic 30 Hz flicker were decreased. Multifocal electroretinography revealed macular dysfunction.ConclusionGanciclovir-associated photoreceptor damage may induce abnormalities in retinal function in response to multiple continuous intravitreal ganciclovir injections at a relatively high dosage (3 mg/0.1 ml).

A nonhuman primate model of blue light-induced progressive outer retina degeneration showing brimonidine drug delivery system-mediated cyto- and neuroprotection

Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) characterized by atrophy of the retinal pigment epithelium (RPE), loss of photoreceptors, and disruption of choriocapillaris. Excessive light exposure is toxic to the retina and is a known risk factor for AMD. We first investigated the effects of blue light-induced phototoxicity on RPE and photoreceptors in nonhuman primates (NHPs, a model of progressive retinal degeneration) and then evaluated the potential cyto- and neuroprotective effects of the brimonidine drug delivery system (Brimo DDS). In the first set of experiments related to model development, parafoveal lesions of varying severity were induced using blue light irradiation of the retina of cynomolgus monkeys to evaluate the level of phototoxicity in the RPE and photoreceptors. RPE damage was assessed using fundus autofluorescence imaging to quantify areas of hypofluorescence, while thinning of the outer nuclear layer (ONL, photoreceptor nuclei) was quantified using optical coherence tomography (OCT). Photoreceptor function was assessed using multifocal electroretinography (mfERG). RPE damage progressively increased across all lesion severities from 2 to 12 weeks, as did the extent of ONL thinning. Lesions of high severity continued to show reduction in mfERG amplitude, reaching a statistically significant maximum reduction at 12 weeks. Collectively, the first set of experiments showed that blue light irradiation of the NHP eye resulted in progressive retinal degeneration identified by damage to RPE, ONL thinning, and disrupted photoreceptor function – hallmarks of GA in humans. We then used the model to evaluate the cyto- and neuroprotective effects of Brimo DDS, administered as a therapeutic after allowing the lesions to develop for 5 weeks. Placebo DDS or Brimo DDS were administered intravitreally and a set of untreated animals were used as an additional control. In the placebo DDS group, hypofluorescence area continued to increase from baseline, indicating progressive RPE damage, while progression was significantly slowed in eyes receiving Brimo DDS. Likewise, ONL thinning continued to progress over time in eyes that received the placebo DDS, but was reduced in Brimo DDS-treated eyes. Pharmacologically relevant brimonidine concentrations were sustained in the retina for up to 26 weeks following Brimo DDS administration. In summary, Brimo DDS demonstrated cyto- and neuroprotective effects in a novel NHP GA model of progressive retinal degeneration.

Evaluation of optical coherence tomography angiography parameters in patients treated with Hydroxychloroquine

BackgroundOne of the major side effects of Hydroxychloroquine (HCQ) is retinopathy. The aim of this study was to evaluate the Optical coherence tomography angiography (OCTA) parameters in a group of patients who have Hydroxychloroquine-induced retinopathy based on Multifocal electroretinography (mfERG) with a group who do not have retinopathy.MethodThis is a Cross-Sectional Study. In this study, patients with Rheumatoid arthritis (RA) or Systemic lupus erythematosus (SLE) who had been taking Hydroxychloroquine for at least 7 years were included. MfERG and OCTA imaging were performed for all patients. Patients were divided into Normal mfERG and Abnormal mfERG groups based on mfERG results. OCTA parameters were studied in these two groups.ResultSixty-one patients (61 eyes) were included. Forty-one patients had SLE and 20 patients had RA. Forty patients (66.7%) had Abnormal mfERG. The mean vascular density (VD) in Superficial capillary plexus (SCP) layer was not significantly different between Normal mfERG and Abnormal mfERG groups (P-Value> 0.05). Mean VD in SCP layer was not significantly different between Normal mfERG and Abnormal mfERG groups (P-Value> 0.05). In RA subgroup, mean VD in SCP layer in PeriFovea region in Abnormal mfERG group was significantly lower than normal group (P-Value < 0.05). Mean VD in deep capillary plexus (DCP) layer in Whole Image, Superior Hemi, Inferior Hemi, PeriFovea area in Abnormal mfERG group was significantly lower than normal group (P-Value < 0.05). This discrepancy was also observed in the RA subgroup but not in the SLE subgroup. The mean of none of the parameters of foveal avascular zone (FAZ) (mm2), Flow Area of Outer Retina (mm2) and Flow Area of Choriocapillaris (mm2) were not statistically significant between the groups Abnormal mfERG and Normal mfERG. (p-value> 0.05).ConclusionVD in the DCP layer decreased in abnormal mfERG patients compared to patients with normal mfERG. But it seems that VD in SCP layer, FAZ Area and Flow Area are similar in both groups. OCTA may be used as a non-invasive tool in the diagnosis of early stages of HCQ-induced retinopathy, especially in RA patients, but further studies are needed.

Multifocalelectroretinography Result before and after Peribulbar Injection of Allogeneic Umbilical Cord – Mesenchymal Stem Cell Secretome for Late-Stage Retinitis Pigmentosa

Background: Retinitis Pigmentosa (RP) is a rare retinal genetic disease without available treatment to date. Previous studies show growth factor and regenerative ability of secretome from cultured allogeneic umbilical chord mesenchymal stem cells (UC-MSC). This studyaimed to report multifocal electroretinography of retinal photoreceptor responsefrom RP patients, before and after injection of secretome from allogeneicUCMSC.Patients and Methods: Four subjects with severely damage retina (visual field defect of 25 %- 50% in initial Humphrey perimetry examination) were recruited and givenperibulbar injection of secretome from allogeneic cultured UC-MSC. Visual acuity, visual field examination, multifocal electroretinogram of retinal photoreceptor examination were observed before and periodically after injection until six months periodResults: Overall, we observed subtle changes in N1 and P1 amplitude and implicit time only in ring 1 at 1, 3 and 6 month post secretome injection. Conclusion: Peribulbar injection of allogeneic UC-MSC secretome had very miminal influence on photoreceptor activity in late-stage RP patients.

Evaluation of Acute Central Serous Chorioretinopathy Using Enhanced Depth Imaging Optical Coherence Tomography and Multifocal Electroretinography

Introduction: The aim of the study was to evaluate functional and structural abnormalities in patients with acute central serous chorioretinopathy (CSC) with multifocal electroretinography (mfERG) and enhanced depth imaging optical coherence tomography (EDI-OCT). Methods: This prospective observational study included 57 patients with unilateral CSC. Both eyes underwent mfERG and EDI-OCT. Peak amplitudes and implicit times of the first kernel responses were analyzed and compared with those of 25 age-matched normal controls. Correlational analyses were performed between the mfERG results and EDI-OCT parameters. Results: Compared with the normal controls, the amplitude and implicit time on mfERG were significantly impaired in the area with serous retinal detachment (SRD) and the area beyond the SRD. Eyes with a greater reduction in SRD had a less impaired mfERG response in fellow eyes than those whose retinal detachments were not spontaneously decreased by >90% after 3 months. Correlational analysis revealed that the subfoveal choroidal thickness was negatively correlated with the mfERG parameters. Conclusions: The findings of this study indicate diffuse functional impairment in acute CSC involving both eyes and areas beyond the SRD. The retinal response of the unaffected eye was associated with regression of SRD. Functional retinal abnormality was found to correlate with pathological changes in the choroid.

An insight on the anatomical and functional consequences of aflibercept therapy in age-related macular degeneration

BackgroundEvaluation of anatomical and functional recovery of the retina after aflibercept therapy in neovascular age-related macular degeneration. Materials and methodsThis prospective study enrolled 33 eyes of 33 naive age-related macular degeneration patients with an average age of 69 (55−82) years. Following a thorough ophthalmological examination, baseline color fundus photography, optical coherence tomography and fluorescein angiography were used to assess the angiographic characteristics and classification of the lesions. Multifocal electroretinography and microperimetry were recorded. In the first three months, all patients received three consecutive intravitreal aflibercept injections on a monthly basis. After the initial three doses, non-responders received additional afibercept injections. The baseline, 3rd and 6th month data were recorded for analysis. ResultsThe baseline average best-corrected visual acuity (1.05 log MAR) improved dramatically to 0.9 log MAR in the 3rd and 6th months, respectively. The baseline average central macular thickness of 358.5 ± 232.1 μm decreased significantly to 273.0 ± 109.9 μm and 245.5 ± 109.3 μm in the 3rd and 6th months, respectively.The average thickness of the central 1 mm macular region decreased significantly from 349.5 ± 96.4 μm to the 3rd and 6th month values of 320.6 ± 101.9 and 290.5 ± 86.4 μm, respectively. While the mean retinal sensitivity increased significantly from 4.7 ± 3.0 dB to 6.9 ± 3.4 Db, local deficit decreased from −11.6 ± 4.6 dB to −9.4 ± 4.6 dB. Significant improvements were also observed in all rings of N1 and P1 waves. ConclusionIntravitreal aflibercept therapy resulted in significant morphological improvements that were easily identifiable during the 3rd month. Electrophysiological improvements were delayed only to become statistically significant in the 6th month. However, it has been shown that visual acuity and optical coherence tomography parameters alone may be insufficient for both the morphological and functional assessment of the retina.

Electrophysiological study after ranibizumab in choroidal neovascularizat

Purpose: To study the effects of intra-vitreal injection of ranibizumab on pattern electroretinogram (PERG) and multifocal electroretinogram(MF-ERG) parameters in choroidal neovascularization and to test the retinal toxicity of ranibizumab. Method: Fifty eyes of 50 patients with subfoveal choroidal neovascularization were included in the study. Thirty (30) eyes had neovascular age related macular degeneration (nAMD) and 20 eyes had myopic choroidal neovascularization. Ranibizumab was injected intravitreal monthly for3 months. Optical Coherence Tomography Angiography (OCT) was performed at the initial and final visits. Visual acuity, Pattern and multifocal electroretinography (PERG, MFERG) were performed before and at 1,2,3,6 months after intravitreal injection. Results: There was no clinical significant reduction of parameters of either MFERG or PERG after intravitreal injection of ranibizumab. There was significant increase in visual acuity, decrease in central macular thickness ,decrease in total macular volume and improvement in the parameters of both PERG and MFERG after intravitreal injection. Conclusion: Intravitreal injection of ranibizumab is effective in treatment CNV and safe. It has no retinal toxicity since no reduction in PERG&amp; MFERG parameters. Keywords: AMD; Ranibizumab; PERG; MFERG

Multifocal Electroretinography as a Method of Functional Assessment of Retinal Laser Injury in Experimental Studies

Purpose: to investigate local functional changes in the rabbit retina by multifocal electroretinography under pulsed laser radiation.Materials and methods. Transpupillary applications by single laser pulses (Nd:YAG laser, 532 nm, 50 ms) with the diameter of the laser beam spot on the retina surface of 132 µm (15 eyes) and 200 µm (15 eyes) were performed on 30 eyes of 15 rabbits. In each eye were applied 6 applications of different laser pulse power (15, 30, 50, 100, 150 and 200 mW). The diameter of the injury zone was assessed ophthalmoscopically and histologically. Multifocal electroretinography was performed before and 30 minutes after exposure using a module for multifocal electroretinography Neuro-ERG (Neurosoft, Russia), topographically comparing a pattern of 61 hexagons with an ophthalmoscopic fundus picture. The amplitude (µV) of the P1 peak and the implicit times (ms) of the P1 and N1 peaks were estimated in the first-order response in the hexagons corresponding to the laser damage zones.Results. When using a laser spot on the retina of 132 microns and 200 microns, the threshold level of laser radiation power for the development of significant local changes in the bioelectric activity of the retina was 50 and 30 mW, respectively (p &lt; 0.05). The minimal diameter of the laser damage at which significant functional changes are recorded by multifocal electroretinography with a pattern stimulator consisting of 61 hexagons was 127.2 ± 6.4 µm (spot 132 µm, energy 50 mW), while a significant relationship was found between changes in the peak amplitude P1 and ophthalmoscopic and histological dimensions of the damage zone (r = 0.73 and r = 0.71, respectively, p &lt; 0.01).Conclusion. The use of multifocal electroretinography can be used to quantify functional changes in local laser damage to the retina in experimental studies on rabbits.

Visual Sequelae of Computer Vision Syndrome: A Cross-Sectional Case-Control Study.

Purpose To assess the visual, ocular, extraocular, and multifocal electroretinography (mfERG) outcomes of computer vision syndrome (CVS) among medical students. Methods This study was designed as a cross-sectional case-control study that included 733 medical students. All students completed a specially designed and validated CVS questionnaire survey (CVS-F3). Students from the control (No-CVS) and CVS groups underwent comprehensive ophthalmic examinations including the mfERG examinations. Our main outcome measures included uncorrected and corrected distance visual acuity (UDVA and CDVA, resp.) measurements, subjective and cycloplegic refractions, slit-lamp examination, intraocular pressure measurement, pupillary reflexes tests, ocular movements' tests, dry eye disease tests, and fundus and mfERG examinations. Results The CVS-F3 identified that 87.9% of students had complaints that might be related to CVS. We documented a 76% prevalence rate in students undergoing an ophthalmologic exam. The most common ocular and extraocular complaints included visual blur and headache (40.9% and 46.8%, resp.). Statistical logistic and linear regression analyses showed that refractive errors, prolonged screen-hours, close eye-screen distance, improper gaze angle, poor screen-resolution, and screen-glare were risk factors for developing CVS and influencing its severity. In the mfERG subgroup, 42.5% demonstrated reduced amplitudes of mfERG rings and quadrants, indicating reduced foveal responses. Conclusion Surveys cannot yield an accurate CVS prevalence. However, they help to identify subjects at risk who should be comprehensively assessed to confirm or exclude CVS diagnosis. Smartphone misuse primarily caused CVS among users. Our mfERG findings might be a sign of potential CVS visual sequelae; however, future studies are warranted. Clinicians need to understand these sequelae to appropriately identify and treat CVS.

Structure-Function Relationship of Retinal Ganglion Cells in Multiple Sclerosis.

The retinal ganglion cells (RGC) may be considered an easily accessible pathophysiological site of degenerative processes in neurological diseases, such as the RGC damage detectable in multiple sclerosis (MS) patients with (HON) and without a history of optic neuritis (NON). We aimed to assess and interrelate RGC functional and structural damage in different retinal layers and retinal sites. We included 12 NON patients, 11 HON patients and 14 healthy controls for cross-sectional multifocal pattern electroretinography (mfPERG) and optical coherence tomography (OCT) measurements. Amplitude and peak times of the mfPERG were assessed. Macula and disc OCT scans were acquired to determine macular retinal layer and peripapillary retinal nerve fiber layer (pRNFL) thickness. In both HON and NON patients the foveal N2 amplitude of the mfPERG was reduced compared to controls. The parafoveal P1 peak time was significantly reduced in HON only. For OCT, parafoveal (pfGCL) and perifoveal (pGCL) ganglion cell layer thicknesses were decreased in HON vs. controls, while pRNFL in the papillomacular bundle sector (PMB) showed reductions in both NON and HON. As the mfPERG derived N2 originates from RGC axons, these findings suggest foveal axonal dysfunction not only in HON, but also in NON patients.

Imaging the pediatric retina: An overview.

Recent decade has seen a shift in the causes of childhood blinding diseases from anterior segment to retinal disease in both developed and developing countries. The common retinal disorders are retinopathy of prematurity and vitreoretinal infections in neonates, congenital anomalies in infants, and vascular retinopathies including type 1 diabetes, tumors, and inherited retinal diseases in children (up to 12 years). Retinal imaging helps in diagnosis, management, follow up and prognostication in all these disorders. These imaging modalities include fundus photography, fluorescein angiography, ultrasonography, retinal vascular and structural studies, and electrodiagnosis. Over the decades there has been tremendous advances both in design (compact, multifunctional, tele-consult capable) and technology (wide- and ultra-wide field and noninvasive retinal angiography). These new advances have application in most of the pediatric retinal diseases though at most times the designs of new devices have remained confined to use in adults. Poor patient cooperation and insufficient attention span in children demand careful crafting of the devices. The newer attempts of hand-held retinal diagnostic devices are welcome additions in this direction. While much has been done, there is still much to do in the coming years. One of the compelling and immediate needs is the pediatric version of optical coherence tomography angiography. These needs and demands would increase many folds in future. A sound policy could be the simultaneous development of adult and pediatric version of all ophthalmic diagnostic devices, coupled with capacity building of trained medical personnel.

Ocular Characteristics of Patients With Bardet-Biedl Syndrome Caused by Pathogenic BBS Gene Variation in a Chinese Cohort.

Bardet–Biedl syndrome (BBS; OMIM 209900) is a rare genetic disease causing damage to multiple organs and affecting patients’ quality of life in late adolescence or early adulthood. In this study, the ocular characteristics including morphology and function, were analyzed in 12 BBS patients from 10 Chinese families by molecular diagnostics. A total of five known and twelve novel variants in four BBS genes (BBS2, 58.33%; BBS4, 8.33%; BBS7, 16.67%; and BBS9, 16.67%) were identified in 10 Chinese families with BBS. All patients had typical phenotypes of retinitis pigmentosa with unrecordable or severely damaged cone and rod responses on full-field flash electroretinography (ffERG). Most of the patients showed unremarkable reactions in pattern visual evoked potential (PVEP) and multifocal electroretinography (mfERG), while their flash visual evoked potentials (FVEP) indicated display residual visual function. Changes in the fundus morphology, including color fundus photography and autofluorescence (AF) imaging, were heterogeneous and not consistent with the patients’ functional tests. Overall, our study expands the variation spectrum of the BBS gene, showing that the ocular characteristics of BBS patients are clinically highly heterogeneous, and demonstrates the usefulness of a combination of the ffERG and FVEP assessments of visual function in the advanced stage of retinopathy in BBS.

The Many Faces of Acute Idiopathic Blind Spot Enlargement

This is a literature review and retrospective case series of acute idiopathic blind spot enlargement of 2 Caucasian females and 1 Hispanic male. Hallmark findings include unilateral photopsia, an enlarged blind spot, loss of the ellipsoid and interdigitation zones on OCT, and an abnormal multifocal electroretinography. This condition is an outer retinal disease that shares common traits with the AZOOR complex, which can confound the diagnosis. Autofluorescent imaging may aid in differentiating the conditions. Disseminating more case reports detailing different presentations of this rare outer retinal disorder help advance the clinical understanding of these conditions.

Impacts of intravitreal anti-VEGF therapy on retinal anatomy and neurophysiology in diabetic macular edema.

To evaluate anatomical and neuroretinal functional aspects in patients with diabetic macular edema (DME) after intravitreal anti-vascular endothelial growth factor (VEGF) therapy, in particular aflibercept. This prospective single-centered interventional study was performed at Afyonkarahisar Health Science University Faculty of Medicine, Department of Ophthalmology, where 32 eyes of 32 patients with DME were investigated. All patients received five intravitreal aflibercept injections on a monthly basis and were followed up for ≥ 6months. After a comprehensive ophthalmological examination, including the measurements of visual acuity and intraocular pressure, and an antero-posterior segment slit-lamp biomicroscopy before and after full pupil dilation, fundus fluorescein angiography and optical coherence tomography were performed at baseline and during the third and sixth months post-therapy. Microperimetry and multifocal electroretinography were also performed at baseline and during the sixth months. Mean visual acuity increased from 0.73 to 0.57 and 0.33 logarithm of the minimum angle of resolution (logMAR) during the third and sixth months, respectively (p < 0.001). Changes in intraocular pressure were not statistically significant (p = 0.472). There was statistically significantly decreased mean central macular thickness from 390.2μm to 242.6 and 289.7μm during the third and sixth months, respectively (p < 0.001). Significantly improved fixation patterns during the sixth month, along with significantly increased macular sensitivity from 8.2 to 14.2dB (p < 0.001) and significantly decreased local deficit from - 10.3 to 5.5dB (p < 0.001) were observed. Further, there was a significantly increased N1 amplitude in the first ring and significantly increased P1 amplitude in all rings (p for each parameter < 0.05). There was also significantly decreased N1 wave implicit time in all rings and significantly decreased P1 wave in the second, third, fourth and fifth rings (p for each parameter < 0.05). Patients with DME showed profound improvement in the retinal neurophysiological function, which was also accompanied by anatomical and ultrastructural integrity recovery after intravitreal aflibercept therapy. In the pathogenesis of DME, the influence of neurodegeneration has been increasingly gaining significant attention. Consequently, the need to assess neurophysiological effects of anti-VEGF therapy using a variety of diagnostic measures like electrophysiological studies and multimodal imaging technologies is undeniably growing.

Long-term full-field and multifocal electroretinographic changes after treatment with ranibizumab in patients with diabetic macular edema.

To investigate changes in macular and panretinal neuroretinal functions by electroretinographic examinations in eyes with diabetic macular edema (DME) treated with intravitreal ranibizumab. Sixty-four patients with DME were included in this prospective study. Patients were treated with ranibizumab injection according to the PRN regimen for over 12months. Before treatment, all patients underwent fundus fluorescein angiography, optical coherence tomography (OCT), best-corrected visual acuity (BCVA) assessment, full-field (ff-ERG), and multifocal electroretinography (mf-ERG). In monthly visits, BCVA and OCT were performed. Besides, mf-ERG recordings were obtained at months 3, 6, 9, and 12, and ff-ERG was performed at month 12. Fifty-eight patients completed the study. The mean age was 61.1 ± 8.5 (39-80) years. The mean number of injections was 6.19 ± 1.9. The decimal BCVA improved from 0.30 to 0.45 during the 12-month follow-up (p < 0.05). Macular thickness decreased from 413.5μm to 329.5μm (p < 0.05). The mf-ERG recordings in the central macular region showed improvements N1 and P1 amplitudes at months 9 and 12. There was a positive correlation between the baseline central (p < 001; r: - 0.378 and p < 0.05; r:-0.335, respectively), the second ring (p < 0.05; r: - 0.260 and p < 0.05; r: - 0.270, respectively) P1- and N1-wave amplitudes, and the BCVA at month 12. Full-field ERG recordings showed that peripheral neuroretinal responses were maintained or improved at month 12. Statistically significant improvements in BCVA and macular thickness were observed at all follow-up visits. Multifocal electroretinographic recording started to improve 6months after the beginning of intravitreal ranibizumab treatment in eyes with DME. This improvement was significant at months 9 and 12. A significant improvement in ff-ERG was observed at month 12.

Myopia-26, the female-limited form of early-onset high myopia, occurring in a European family

BackgroundFemale-limited early-onset high myopia, also called Myopia-26 is a rare monogenic disorder characterized by severe short sightedness starting in early childhood and progressing to blindness potentially by the middle ages. Despite the X-linked locus of the mutated ARR3 gene, the disease paradoxically affects females only, with males being asymptomatic carriers. Previously, this disease has only been observed in Asian families and has not gone through detailed investigation concerning collateral symptoms or pathogenesis.ResultsWe found a large Hungarian family displaying female-limited early-onset high myopia. Whole exome sequencing of two individuals identified a novel nonsense mutation (c.214C>T, p.Arg72*) in the ARR3 gene. We carried out basic ophthalmological testing for 18 family members, as well as detailed ophthalmological examination (intraocular pressure, axial length, fundus appearance, optical coherence tomography, visual field- testing) as well as colour vision- and electrophysiology tests (standard and multifocal electroretinography, pattern electroretinography and visual evoked potentials) for eight individuals. Ophthalmological examinations did not reveal any signs of cone dystrophy as opposed to animal models. Electrophysiology and colour vision tests similarly did not evidence a general cone system alteration, rather a central macular dysfunction affecting both the inner and outer (postreceptoral and receptoral) retinal structures in all patients with ARR3 mutation.ConclusionsThis is the first description of a Caucasian family displaying Myopia-26. We present two hypotheses that could potentially explain the pathomechanism of this disease.