Multifocal electroretinogram changes in axial high

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Abstract:

Purpose: To measure changes in retinal functions in response to elongation of the axial length (AL). Methods: This is a cohort prospective study in which 15 patients aging 18-40 years with spherical equivalent (SE) of ?-5 were included. A thorough ocular examination was done and a standard multifocal electroretinogram (mfERG) was performed. Results: A total of 30 eyes that were completely normal except for long AL with normal or tessellated fundi. The mfERG showed varying reductions in amplitudes (amp.) as well as elongations of Implicit times (Imp.

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T), of both P1 and N1 components, at almost all rings and quadrants. Conclusion: Retinal functions at different layers were significantly affected by the extension of the AL, and that increases as the axial length increases.

Introduction:

Researchers argued the definition of high myopia, with a spherical equivalent of -5.00 diopter (D) or less as the most agreed definition. High myopia is a great challenge because, it exposes the eye towards pathological changes and complications such as, but not limited to, glaucoma; retinal detachment (RD); macular degeneration; and cataract [1].

The pathological consequences arise in 30-50% of highly myopic patients, and those pathologies have taken the attention of lots of studies. However, studies lack enough information about high myopia in otherwise normal eyes [2].

The multifocal electroretinogram (mfERG) is a new recording technique for retinal function, which is capable of measuring functions of multiple retinal locations, within the central 40-50%, simultaneously. Its ability to make a topography of retinal functions and/or lesions has lent it a privilege over the other retinography techniques[3].

There is consensus between studies that the mfERG response is negatively affected in myopia. Almost all studies reported decreased amplitudes and elongated implicit times, and that these changes intensify as the degree of myopia increases[4][5][6]-[8]. In addition, myopia is mainly due to the axial component, with the refractive part playing a minor role [9].

Studies showed no doubt that retinal function, mfERG response, reduces with elongation of the axial length. However, there were different results regarding the most affected location and/or interpretation of the analysis of the cause [10][9][11][6].

As mfERG is influenced by ethnicity [12] and there is scanty of data about the affect of axial high myopia on the mfERG response in Egyptians. Therefore, this study provides additional data regarding that issue.

Patients and Methods:

Study design: a prospective, observational study. This study was conducted according to the world medical association's declaration of Helsinki and ethically approved by the ethics committee of the Al-Azhar's faculty of medicine.

Patients criteria: Among 25 patients randomly selected for the study, 2 refused to be included and 8 had fundus changes that are not compatible with the study. So, this study was carried out on 15 patients who attended the refractive unit, Ophthalmology department, hospitals of the Al-Azhar University of Cairo between June 2018 and December 2018. All included patients (males and females) were aging from 18 to 40 years, with high myopia of -5.00 diopter (D) or less and axial length of 26mm or more. Those who refused to consent as well as those having any opaque media or any retinal lesion except for tessellated fundus were excluded.

Evaluation: All participants were evaluated for visual acuity (VA) using the Snellen's chart; refraction using Topcon auto refractometer, model KR-800PA; best-corrected visual acuity (BCVA) with trial glasses and lenses in place on the Snellen's chart; intraocular pressure (IOP) using Topcon, model CT 80, using the air-puff technique; color vision using Ishihara test; anterior segment examination (for any media opacity) using the Topcon slit-lamp, model SL-D701; posterior segment examination (for any fundus abnormalities) using the slit-lamp with Hruby 90D and 78D lenses; the axial length (AL) using the Topcon Aladdin biometer with corneal topography. Written informed consent was taken from the patients. This study was conducted according to the world medical association's declaration of Helsinki and ethically approved by the ethics committee of the Al-Azhar's faculty of medicine.

Technical parameters: The multifocal electroretinogram (mfERG) was recorded, according to the international society of the clinical electrophysiology of vision (ISCEV), using the Reti-port/ Scan 21 system (Roland Consult, Germany). The stimulus was delivered on a 20-inch Cathode ray tube (CRT) monitor presenting 61 hexagons in the pseudo-binary m-sequence with a frame rate of 60 Hertz (Hz) at a distance of 33cm and viewing angle of 27 degrees. The maximum luminance was 120cd/m2 for the white stimulus and 2cd/m2 for black stimulus. The active corneal electrode was the HK-loop electrode and was put in the lower fornix, the reference electrode was put on the skin near the ipsilateral outer canthus and the ground electrode was put on the forehead. The impedance was kept below 5 K Ohm.

Clinical protocol: All patients were tested at 11 AM to avoid the effect possibility of the circadian rhythm. Patients were adapted to moderate to dim room light for 15min before the test with the pupils fully dilated to more than 7mm with 1.0% tropicamide hydrochloride. Patients were facing the middle of the screen and best-corrected for the distance. The anesthetic drop of topical benoxinate hydrochloride 0.4% was instilled. Patients were binocularly tested for 6 min with a break at every 45 sec and monitored for fixation by a camera attached to the screen.

Interpretation of the results: P1 amplitude was measured from the trough of the A1 to the peak of the P1; P1 implicit time was measured from the start of the stimulus to the peak of the P1 wave. N1 amplitude was measured from the baseline to the trough of the N1; N1 implicit time was measured from the start of the stimulus to the N1's trough. Summed responses were taken in concentric rings around the fovea, with areas (deg2) of 12.6; 17.9; 26.2; 36.5 and 48.6. Scaled amplitudes, as more accurate, were taken, and the response was divided into 4 quadrants (Q1 the superior nasal; Q2 superior temporal; Q3 inferior temporal; Q4 inferior nasal) around the fovea.

Statistical analysis: Responses between different rings and between different quadrants were collected into Excel sheets and statistically analyzed using the Statistical analysis software (SAS) v9.4 and Minitab software v18. Student t-test was done in SAS to obtain significance of statistical data. In addition, Pearson correlation and Regression analysis formula was done in Minitab to find types of relations and compare values, respectively.

Results:

Among 25 patients randomly selected for the study, 2 refused to be included and 8 had fundus changes that are not compatible with the study. Therefore, we had 15 patients as plotted in the table (1), 10 males and 5 females, with eye numbers of 30. Their mean age was 30.7y ± 5.2 standard deviation (SD). Their mean myopic spherical equivalent (S.E) was -12.9 D ± 3.5 SD. Their mean axial length (AL) was 28.33mm ± 0.96 SD. The range for the S.E and the AL was 8.78 D and 2.72 mm, respectively.

Emmetropia High myopia

Number of subjects 15 15

Number of eyes 30 30

Age (y) 21:39 19:38

Sex 7M:8F 10M: 5F

Axial length (mm) 23.2 ± 0.79 28.3 ± 1

Refraction (D) (+0.25: -0.25) ± (-0.1: +0.1) -12.9 ± 3.2

Different parameters among groups

There was a range of changes as follows:

P1 amp. (?V) P1 Imp.T (ms) N1 amp. (?V) N1 Imp.T (ms)

Range ± SD Range ± SD Range ± SD Range ± SD

Rings

R1 1.43 ± 0.5 R1 15.7 ± 5.7 R1 0.77 ± 0.31 R1 9.8 ± 3.2

R2 1.02 ± 0.4 R2 10.8 ± 4 R2 0.54 ± 0.22 R2 12.8 ± 4.8

R3 0.81 ± 0.3 R3 8.8 ± 3.4 R3 0.334 v 0.13 R3 6.8 ± 2.5

R4 0.51 ± 0.2 R4 8.9 ± 3.6 R4 0.28 ± 0.09 R4 4.9 ± 2.3

R5 0.2 ± 0.07 R5 4.7 ± 2 R5 0.15 ± 0.05 R5 3.9 ± 1.7

Quadrants

Q1 0.39 ± 0.15 Q1 6.9 ± 2.6 Q1 0.19 ± 0.07 Q1 3.9 ± 1.57

Q2 0.48 ± 0.2 Q2 8.9 ± 3.15 Q2 0.3 ± 0.1 Q2 4.8 ± 2.24

Q3 0.82 ± 0.3 Q3 8.9 ± 3.4 Q3 0.49 ± 0.19 Q3 5.9 ± 2.2

Q4 0.41 ± 0.14 Q4 6.9 ± 2.6 Q4 0.16 ± 0.05 Q4 11.7 ± 4.6

Ring analysis

The P1 amplitudes (µV) were negatively correlated with the axial length; the longer the axial length, the more reduced is the amplitude. That correlation was significant for the rings 1,2,3,4 and 5 with a P-values of .001, .001, .0001, .0001, .0001, respectively.

Emmetropia (Mean ± SD) Axial myopia (Mean ± SD) Percentage of change P-value

Ring 1 1.655 ±0 .33 0.68 ± 0.5 -59% 0.001

Ring 2 1.335 ± 0.26 0.52 ± 0.4 -61% 0.001

Ring 3 1.255 ± 0.34 0.5 ± 0.32 -60% 0.0001

Ring 4 1.32 ± 0.30 0.44 ± 0.2 -67% 0.0001

Ring 5 1.185 ± 0.30 0.36 ± 0.06 -69% 0.0001

Table (1): Rings P1 amplitudes (?V/deg?)

There were significant delays in the P1 peak times for the rings 2,3,4 and 5 with a P-values of .019, .023, .05, .031, respectively. Although P1 peak time in ring 1 was changed, the change was not significant.

Emmetropia (Mean ± SD) Axial myopia (Mean ± SD) Percentage of change P-value

Ring 1 39.915 ± 0.31 50.3 ± 5.7 26% 0.072

Ring 2 37.105 ± 0.37 47.5 ± 4 28% 0.019

Ring 3 37.835 ± 0.36 46.9 ± 3.3 24% 0.023

Ring 4 37.9 ± 0.30 46.03 ± 3.6 21% 0.051

Ring 5 39.24 ± 0.32 45.85 ± 2.05 17% 0.031

The N1 amplitudes were also diminished as the axial length increases. Significant changes were detected in rings 2,3,4,5 but not in ring 1. Their p-values are .004, .0001, .0001, .0001 and .099, respectively.

Emmetropia (Mean ± SD) Axial myopia (Mean ± SD) Percentage of change P-value

Ring 1 0.7 ± 0.30 0.47 ± 0.31 -33% 0.099

Ring 2 0.605 ± 0.33 0.24 ± 0.22 -60% 0.004

Ring 3 0.58 ± 0.31 0.22 ± 0.13 -62% 0.0001

Ring 4 0.665 ± 0.30 0.17 ± 0.09 -74% 0.0001

Ring 5 0.65 ± 0.30 0.16 ± 0.05 -76% 0.0001

Table (3): Rings N1 amplitudes (?V/deg?)

The N1 peak times were also significantly delayed in all rings except ring 2. The p-values were .005, .083, .019, .016, .005 for rings 1,2,3,4,5 respectively.

Emmetropia (Mean ± SD) Axial myopia (Mean ± SD) Percentage of change P-value

Ring 1 19.55 ± 0.56 30.6 ± 3.2 57% 0.005

Ring 2 18.93 ± 0.38 27.3 ± 4.8 44% 0.083

Ring 3 18.08 ± 0.31 25.8 ± 2.5 43% 0.019

Ring 4 18.685 ± 0.40 27.3 ± 2.3 46% 0.016

Ring 5 19.05 ± 0.34 29.1 ± 1.7 53% 0.005

Quadrants analysis

The P1 amplitudes (µV) were negatively correlated with the axial length; the longer the axial length, the more reduced is the amplitude. That correlation was significant for the quadrants 1,2,3,4 with a P-values of .002, .001, .003, .001, respectively.

Emmetropia (Mean ± SD) Axial myopia (Mean ± SD) Percentage of change P-value

Quadrant 1 0.875 ± 0.30 0.38 ± 0.15 -57% 0.002

Quadrant 2 1 ± 0.34 0.47 ± 0.2 -53% 0.001

Quadrant 3 1.025 ± 0.31 0.48 ± 0.30 -53% 0.003

Quadrant 4 0.92 ± 0.33 0.34 ± 0.13 -63% 0.001

Table (5): Quadrants P1 amplitudes (?V/deg?)

There were significant delays in the P1 peak times for the quadrants 1, 2, 4 but not quadrant 3 with a P-values of .032, .031, 03, .102, respectively.

Emmetropia (Mean ± SD) Axial myopia (Mean ± SD) Percentage of change P-value

Quadrant 1 39 ± 0.32 46.2 ± 2.6 18% 0.032

Quadrant 2 39.005 ± 0.30 46.8 ± 3.15 20% 0.031

Quadrant 3 39.24 ± 0.64 45.8 ± 3.4 17% 0.102

Quadrant 4 39.135 ± 0.73 46.35 ± 2.6 18% 0.03

The N1 amplitudes were significantly diminished as the axial length increases. Significant changes were detected in quadrants 1, 2, 3, 4 with p-values of .0001, .0001, .001, .0001, respectively.

Emmetropia (Mean ± SD) Axial myopia (Mean ± SD) Percentage of change P-value

Quadrant 1 0.58 ± 0.37 0.18 ± 0.06 -69% 0.0001

Quadrant 2 0.655 ± 0.30 0.2 ± 0.1 -71% 0.0001

Quadrant 3 0.645 ± 0.33 0.22 ± 0.18 -65% 0.001

Quadrant 4 0.6 ± 0.31 0.11 ± 0.05 -81% 0.0001

Table (7): Quadrants N1 amplitudes (?V/deg?)

The N1 peak times were also significantly delayed in all quadrants except quadrant 4. The p-values were .004, .025, .01, .106, for quadrants 1,2,3,4, respectively.

Emmetropia (Mean ± SD) Axial myopia (Mean ± SD) Percentage of change P-value

Quadrant 1 18.815 ± 0.36 28.2 ± 1.5 50% 0.004

Quadrant 2 18.845 ± 0.32 26.6 ± 2.2 42% 0.025

Quadrant 3 19.12 ± 0.57 28.2 ± 2.2 47% 0.01

Discussion:

This study in the general frame was about high myopia is spreading worldwide in a terrifying way. The number of highly myopic patients was 163 million or 2.7% of the world population in the year 2000 and calculated to reach approximately 1 billion or 10% of the world population by the year 2050. In other words, the world will be up to 5-times increase in high myopic population by 2050 [1]. There is lack of data about burden of high myopia in Egyptian population with only one study, as far as we know, estimated that pathological myopia affects 10.9% of Egyptians aging from 15-75 years old, with 22.5% and 77.5% were unilaterally and bilaterally affected, respectively [13].

The area of focus of this study was chosen because studies lack enough information about high myopia in otherwise normal eyes [2]. In addition, the mfERG response is influenced by ethnicity [12] and there is scanty of data about the affect of axial high myopia on the mfERG response in Egyptians. Additionally, studies showed varying patterns of affection among different study groups. Therefore, we aim to participate in making electrophysiological data about the Egyptian population.

The patients were randomly selected based on criteria that isolate the focus of this study; the axial length and the retinal function. For instance, media opacities [14], [15]; DM [16]-[19]; systemic HTN [20], medications [21], RD [3], glaucoma [22], ARMD [23] and any retinal disorders, even myopic fundus changes. Therefore, every participant went through a complete ocular evaluation and systemic assessment of any condition and/or medication that can affect the eye and/or the visual pathway.