said the highest age range for DME was 50-59 years old as much as 51.4%. The pathogenesis of DME is also associated with an increase in VEGF due to hyperglycemic conditions, when VEGF levels increase it can cause blood plasma leakage and hypoxia of the tissue.
Optical coherence tomography examination is an easy method in assessing macular thickening.
Microperimetry can assess retinal sensitivity at the right location because it can choose the location to be examined from the fundus image.
One of the newest tools for microperimetry examination is MP3, this tool can perform fundus image tracing automatically. DME pathology needs to be evaluated both functionally and structurally, so microperimetry is needed because it can assess retinal sensitivity.
Evaluation of the correlation of functional changes using MP3 microperimetry and structural changes of the macula using OCT in DME patients is interesting to do so that authors are interested in evaluating the correlation of microperimetry MP3 and OCT examination.
SUBJECT DAN METHOD
This study is an analytic observational study with a cross- sectional design, then correlation analysis was performed. Sampling was done by a consecutive sampling of patients who came to the Vitreoretinal unit who met the inclusion criteria, good results of MP3 microperimetry and OCT examination, patients aged 40-70 years with a diagnosis of DR with DME with fovea involvement.
Exclusion criteria were MP3 microperimetry and OCT imaging with poor reliability, significant refractive media opacification, history of intraocular surgery, history of other retina abnormalities such as macular ischemia, disorganization of the retina inner layer (DRIL). Data collection was carried out after approval from the research ethics committee of the National Eye Center Cicendo Eye Hospital Bandung.
The data taken were age, gender, DR classification, duration of DM, HbA1c levels, eye laterality, MP3, and OCT microperimetry results.
Statistical analysis used the Kolmogorov-Smirnov test (z) to test the normality of the data and the correlation test with Spearman (ρ).
Interpretation of the results based on the strength of the correlation, the direction of the correlation and the p- value. Calculation of correlation strength (r), based on the criteria of Guilford (1956). Processing data using Microsoft Excel 2013 and SPSS version 25. The results of the analysis are presented in tabular form to facilitate data visualization.
MP3 Microperimetry
The MP3 microperimetry examination is similar to the perimetry test, the examination is carried out in a dark room with one eye alternately, the other eye is occluded then the patient will be given a light stimulus and asked to press the tool when viewing the stimulus. MP3 microperimetry is automatic retinal tracking, that is, the stimulus received is always in the same area on the fundus so that it gets more accurate results. The light stimulus given starts from 0-20
decibels in each pattern from 56 locations in different macular areas and the central point is on the fovea in the form of a 1-degree red circle, for this study a 17 dB light stimulus was used. Parameters that can be assessed from microperimetry examination are the average sensitivity in decibels and the fixation quality of the patient.
Results with 18 dB can be assessed as normal retinal sensitivity and below that is decreased sensitivity. The patient's fixation is said to be stable if 75% of the total fixation falls on a 4- degree circle area and unstable if it is less than 75%.
Optical Coherence Tomography OCT technology has the principle of low coherence interferometry, where light with low coherence is emitted to the target tissue, then the light reflected back by the tissue will be combined with a second light beam or reference beam. The results of the resulting interference pattern will be used to reconstruct an axial A-scan, which describes the scattering ability of each network in the light beam path. Moving the light in a line on the tissue will result in a compilation of A-scans that can be used to reconstruct a B-scan. Repeating several B-scans at several adjacent locations can produce information about the condition of the volume of the structure in 3 dimensions.
The examination was carried out one by one in each eye of the patient and asked to focus on the fixation target on the machine. OCT examination was obtained by selecting the type of macular cube scan 512x128. The value listed in each eye is recorded as the value for macular thickness.
RESULT
This study was conducted at the Vitreoretinal and Diagnostics Unit of PMN Cicendo Eye Hospital Bandung in September – October 2021. Based on the data collected, a total of 57 patients and 61 eyes were included in the inclusion criteria in DME patients who underwent macular OCT and MP3 Microperimetry.
Table 4.1 Characteristics of Research Subject
Variable N=57
(patient) Number of Patients 57(100.0%) Number of Eyes* 61(100.0%) Age (years)
Young Adults (40-50) 16(28.1%)
Adults(51-60) 29(50.9%)
Elderly (>60) 12(21.1%) Sex
Male 28(49.1%)
Female 29(50.9%)
DM duration (years)
Median 10.00
Range (min-max) 3.00-20.00 HbA1c
<6.4% 4(7.0%)
>6.5% 53(93.0%)
Laterality
Unilateral 53(93.0%)
Bilateral 4(7.0%)
Diagnosis DR
Moderate NPDR 2(3.5%)
Severe NPDR 41(71.9%)
PDR 14(24.6%)
Anti VEGF therapy
No 30(52.6%)
Yes 27(47.4%)
Description: Categorical data is presented with number/frequency and percentage, while numerical data is presented with median and range. * N number of eyes
Table 4.1 describes the characteristics of the study subjects based on age, sex, duration of DM, HbA1c levels, laterality, DR classification, and history of previous anti-VEGF therapy. The total number
of patients was 57 people with a total of 61 eyes. For patients with the age category of young adults as many as 16 people (28.1%), adults as many as 29 people (50.9%) and elderly people as many as 12 people (21.1%). 28 male patients (49.1%) and 29 female patients (50.9%). For patients with unilateral laterality as many as 53 people (93.0%) and bilateral as many as 4 people (7.0%).
Patients with a median duration of DM 10 years with HbA1c levels in the category <6.4% were 4 people (7.0%) and >6.5% were 53 people (93.0%).
The diagnosis of DR in each patient with DME with moderate NPDR was 2 people (3.5%), severe NPDR was 41 people (71.9%) and PDR was 14 people (24.6%). A total of 30 people (52.6%) had not received anti-VEGF therapy before and 27 people (47.4%) had received therapy.
Table 4.2 describes the correlation between macular thickness and retinal sensitivity. In the decreased retinal sensitivity group, the macular thickness had a median of 426 m (range 307-612) and the normal retinal sensitivity group of 362.5 m (range 325-379). This numerical data
analysis was tested using the Mann Whitney test because the data were not normally distributed, namely the variable thickness of the macula. The results of statistical tests in the research group above obtained information on the P value of the macular thickness variable less than 0.05 (P value> 0.05) which means statistically significant or significant, thus it can be explained that there is a statistically significant mean difference between the variables of macular thickness in the group.
decreased and normal.
In accordance with table 4.3 from the statistical analysis of the Spearman correlation test between the variables of macular thickness and retinal sensitivity, the p-value for the correlation between macular thickness and retinal sensitivity has a significant value or p-value of 0.0001 where the p-value is less than 0.05 (p- value <0.05). This shows a significant or statistically significant correlation, so it can be concluded that there is a correlation between each variable of macular thickness and retinal sensitivity.
Table 4.2 Correlation of Macular Thickness and Retinal Sensitivity Variable
Sensitivity retina
p-value
Decrease Normal
N=55 (eye) N=6 (eye)
Macular Thickness 0.006*
Median 426.00 362.500
Range(min-max) 307.00-612.00 325.00-379.00
Description: For numerical data, the p-value was tested by unpaired t-test if the data were normally distributed with the alternative of the Mann Whitney test if the data were not normally distributed. The significance value is based on the p-value < 0.05. The * sign indicates the p-value < 0.05, which means that it is statistically significant or significant.
Table 4.3 Table of Correlation Analysis of Macular Thickness with Retinal Sensitivity
Variable Correlation R p-value
Macular Thickness Correlation with Retinal Sensitivity Spearman -0.823 0.0001**
Macular Thickness Correlation with Macular Sensitivity
in Untreated Patients Spearman -0.820 0.0001**
Macular Thickness Correlation with Macular Sensitivity in Patients who have been Treated
Spearman
-0.857 0.0001**
Description: Significance value of p < 0,05. Sign ** indicates significant or statistically significant. R:
correlation coefficient
Correlation coefficient value (R) obtained information that the direction of the correlation is negative with a strong correlation strength using Spearman statistical analysis, then the r-value for the correlation value of macular thickness with retinal sensitivity is -0.823; p-value = 0.0001, in patients who have not been treated by -0.857; p-value = 0.0001, in patients who have received therapy, is -0.820; p-value = 0.0001; This shows that there is a significant correlation with the direction of the negative and strong correlation between macular thickness and retinal sensitivity. After going through the test and the results are significant, the Guilford criteria can be used to determine the closeness of the relationship, so it can be concluded that there is a strong and significant correlation or relationship between macular thickness and retinal sensitivity in both patients who have not received therapy and have received therapy.
DISCUSSION
The characteristics of the subjects in this study included age, gender, duration of suffering from DM,
HbA1c levels. These data were obtained through history taking and clinical examination. Based on table 4.1, it is found that the proportion of patients with female gender is more than male. This result is in accordance with the Riskesdas 2018 data which reported 1.8% female DM patients in Indonesia, more than 1.2% male.
These results are related to the fact that more men work and carry out activities so that DM exposure is lower than women. Adults (51-60) years old have more DM exposure than young adults and the elderly.
This is in accordance with Riskesdas 2018 data showing the largest proportion of DM is in the range of 55-64 years (6.3%). Overall the median duration of DM patients was 10 years (range 3.00–20.00). In contrast to studies conducted by El- magid et al, it is said that subclinical diabetic retinopathy occurs in the range of 4-8 years. This could be due to better adherence to medication and blood sugar control in the patients in this study, as many as 93% had HbA1c levels > 6.5%. Most of the subjects in this study were late for an early eye examination and an eye
examination was carried out after symptoms of blurry vision. A total of 71.9% of patients diagnosed with DME are in the severe NPDR classification. Diabetic macular edema can occur in any DR classification so that the DME classification is distinguished from the DR classification.2,3,24,25
Palkovits et al assessed retinal sensitivity using MP3 microperimetry in patients with healthy macular conditions and patients with macular disorders. The study stated that retinal sensitivity testing using MP3 microperimetry had adequate results in patients with macular disorders.
The use of MP3 microperimetry can also assess the progression of macular disorders and the success of therapy by routinely assessing retinal sensitivity. A similar study was also conducted by Nagpal et al. using MP3 microperimetry compared with OCTA to assess macular degeneration. The study said that MP3 microperimetry can be used to assess the success of therapy given to patients with macular degeneration by routinely performing MP3 microperimetry examinations.22,23 The relationship between macular thickness using OCT examination and retinal sensitivity using MP3 microperimetry examination in the normal and decreased retinal sensitivity groups showed a statistically significant difference. In this study, the median macular thickness in the retinal sensitivity group decreased by 426 m (range 307-612). Vujosevic et al compared changes in retinal sensitivity using MP1 microperimetry examination of macular thickness in several DME classifications. Based on this study,
the mean macular thickness in the clinically significant macular edema (CSME) group was 390.4±93.8µm using OCT and the average retinal sensitivity was 4.7±3.5 dB. The study also reported that there was no significant correlation between mean macular thickness and retinal sensitivity in the no macular edema (NE) and non clinically significant macular edema (NCSME) groups, but there was a significant correlation in the CSME group. Retinal neovascular changes in DME can cause damage to the blood-retinal barrier resulting in a thickening of the retinal layer, it can also cause retinal ganglion cell dysfunction so that retinal sensitivity will decrease. The research of Vujosevic et al. is in accordance with this study in tables 4.2 and tables 4.3, that is, there is a significant correlation between macular thickness using OCT examination and retinal sensitivity using MP3 microperimetry both in patients who have not been treated and have received anti-VEGF therapy. Factors that cause macular edema and decreased retinal sensitivity are also associated with increased anti-VEGF levels because they can cause blood plasma leakage and tissue hypoxia.
This causes when DME occurs it will also cause a decrease in retinal sensitivity which is assessed using OCT and MP3 microperimetry.25,26 Macular thickness after anti- VEGF therapy may decrease, due to decreased anti-VEGF so that damage to the blood-retinal barrier and increased capillary permeability will not occur. This causes the accumulation of fluid in the retina to decrease. A decrease in macular thickness directly results in good
retinal sensitivity as long as DRIL does not occur. This is in accordance with this study in Table 4.3, which found a statistically significant correlation between macular thickness and retinal sensitivity in patients who had received anti-VEGF therapy. 25,26
The limitation of this study is that sampling was only done at one visit, so that in assessing the progressive decrease in macular thickness with retinal sensitivity it has not been able to provide a maximum picture. Other factors that have a relationship with retinal sensitivity are also possible to influence the results of the study, such as some subjects who have received anti-VEGF therapy.
CONCLUSION
There is a correlation between the results of OCT examination in the form of macular thickness and MP3 microperimetry examination in the form of retinal sensitivity in DME patients. The results of this study can be used as a basis for further cohort studies in assessing the success of therapy in DME patients using OCT correlation and MP3 microperimetry.
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