Effective converting ratio when switching between Ona-botulinumtoxin-A and Abo-botulinumtoxin-A in cervical dystonia. A patient assessment cross over study- Juniper Publishers

 

Neurology & Neurosurgery- Juniper Publishers

Introduction

In the 1950s it was hypothesized that Botulinum Neurotoxins (BoNT-A’s) could be used to reduce activity in muscle disorders [1]. Botulinum neurotoxin is made of a gram-positive anaerobic bacterial exotoxin-

clostridium botulinum [2]. When injected in the skeletal muscle, the botulinum toxin inhibits vesicular neurotransmitter (acetylcholine) release at the neuromuscular junction at the presynaptic membrane and a local chemo-denervation appears [1]. Thereby the toxin can reduce muscular contraction, which is the desire to reduce overactive muscle activity [3-5]. The medical therapies for dystonia are effective, and studies have shown that botulinum toxin is the most effective treatment for cervical dystonia [6]. The evidence from several Class I and Class II studies has led to a level A recommendation for use of BoNT-A for treating focal dystonia such as cervical dystonia, hemifacial spasm and blepharospasm [7]. Three main BoNT-A products are available on the market today: Ona-botulinumtoxin-A (Botox®), Abo-botulinumtoxin-A (Dysport®) and Inco-botulinumtoxin (Xeomin®). Due to different production methods, the biological nature of the three BoNT-A’s are different (e.g. the protein load, formulation, pH, dose and immunogenicity). Moreover, the BoNT-A’s are not interchangeable on an equivalent-dose basis [1, 7].

Study background

The goal of this study was to find the optimal conversion ratio for patients with cervical dystonia when switching treatment between Abo-botulinumtoxin-A and Ona-botulinumtoxin-Awhile obtaining a stable satisfying symptom improvement based on a subjective patient assessment. There is heterogeneity in treatment strategies and on how doses and the effect of BoNT-As are reported until now. This study represents a retrospective (follow-up), cross-over study (each patient acts as his/her own control). Effect of treatment was based on individual patient assessment. Individual based conversion rates were calculated using the optimal treatment dose for Abo-botulinumtoxin-A and Ona-botulinumtoxin-A. Due to the length of the present study with a follow-up time from 1991 to end 2014, it was possible to find stable toxin doses where each patient felt the best effect (min. 90%, VAS-score).

Methods

Study design

The clinical data was sampled from the patients’ medical records. Dystonic muscles and injection sites were identified by using electromyography (EMG). The neurologist determined the toxin doses based on each patient´s disease condition and the dystonic muscles activity (EMG). Each treatment (dosing) pr. clinical visit was individualized. At each consultation the neurologist reported the data (doses of toxin and the patient assessed effect and side effects) in the internal IT-system (Danish electronical patient journal) and also used standard sketches of the face/neck-regions to note which muscles have been injected

Botulinum toxin treatment

Ona-botulinumtoxin-A was diluted with saline to a concentration of 40U/ml. Abo-botulinumtoxin-A was dilutedwith saline to a concentration of 200 U/ml. For cervical dystonia the injection sites were between 2-8 sites. The injection doses in the specific muscles pr. patient and the total botulinum toxin doses pr. consultation were registered.

Effect of the procedure

The patients received treatment with BoNT-A´s every 3rd month at the neurological movement disorder clinic by an experienced neurologist. The subjective assessment of maximal treatment effect on dystonia symptoms between each treatment visits, were evaluated at each visit by the patient on a horizontal 100-mm Visual Analogue Scale (VAS) ; where the left end point indicated 0% treatment effect (no change in dystonia symptoms and no effect of the botulinum toxin) and the right end point indicated a total 100% treatment effect (indicate no dystonia symptoms and a maximal effect of botulinum toxin) between treatments)[8-11].

Data collection

In this study, data was only obtained from patients with a stable idiopathic cervical dystonia, and no change in relevant medical treatment over the data recording period. (Patient study entry, Table 1). The mean individual dose of Onabotulinumtoxin- A was obtained from 4 continuous consultations from each patient with a symptom relief of >90%. The treatment was then changed to Abo-botulinumtoxin-A after filtration to maximal effect and the mean individual dose of this toxin was obtained in the same manner as Ona-botulinumtoxin-A. The conversion ratio of Ona- & Abo-botulinumtoxin-A could then be calculated for each individual by dividing the mean individual Ona-botulinumtoxin-A dose with the mean Abobotulinumtoxin- A dose. The final average conversion ratio (Ona- BoNT-A: Abo-BoNT-A) in the study was found by using all the individual conversion ratio data from the 48 patients (Figure 1).

Statistical analysis

For our statistical analysis of our data we used the software package SPSS Statistics. All averages are in mean± standard deviation.

Results

625 out-patients in total were registered at the movement disorder clinic and received treatments with botulinum toxins. Of these, 48 patients with cervical dystonia patients met the inclusion criteria (Figure 2).

Cervical treatment was determined by the level of dystonia and ranged between 25- 200 units (Ona-botulinumtoxin-A) and 125- 775 units (Abo-botulinumtoxin-A) pr. clinical visit. More females had dystonia and most of the patients’ ages were between middle 50s to middle 70s (Table 2). All data wascollected in a period of 25 years from the movement disorder clinic. The VAS-outcome for each patient was minimum 90%. This retrospective data formed a cross-over design as each patient acted as his/her own control. Therefore, patients with confounders such as smoking, obesity etc. and comorbidities such as heart and lung diseases were not excluded, due to the cross over design. The average treatment time for patients with cervical dystonia receiving Ona-botulinumtoxin-A and Abobotulinumtoxin- A was 15,8±4,6 years. This average treatment time is the total period before and after switching botulinum toxin-A. 2546 injection series (total) were analyzed. Doses were 126 ± 38,8 IE-U for Ona-botulinumtoxin-A and 381,6 ± 151,1 IE-U for Abo-botulinumtoxin-A (Table 3). The mean conversion ratio for cervical dystonia was 1: 2.56. (Table 4).

Discussion

We are reporting 55 patients who converted treatment between Abo- and Ona-botulinumtoxin-A. All data wascollected in a period of 25 years from the movement disorder clinic. Patients have been stabilized with the Ona- or Abobotulinumtoxin- A treatment for at least a year before crossing over to treatment with the other toxin. Due to the long followup and moderate amount of data, we were able to find the average conversion ratio based on each patient´s subjective assessment. Former reports show no statistically significant difference on duration of the effect or adverse effects between Ona-botulinumtoxin-A and Abo-botulinumtoxin-A [12]. Data in these topics were excluded and not evaluated here. Treatment effect of Ona-botulinumtoxin-A and Abo-botulinumtoxin-A was in this study assessed by the treated patients. Due to the routine feedback from each of the treated patients over several years it was possible to achieve regular measurement of treatment effect from a subjective patient perspective without extra time for objective observations and evaluation in between toxin treatment sessions. The conversion ratio between the toxins (Ona-BoNT´s and Abo-BonT´s) using a patient-based assessment has in the present study shown to be equal to the study where they were using multicenter double-blind randomized trials [13]. Due to risk of different treatment techniques, toxin diffusion and especially individual variation in differentiating on relevant pain, a 90% margin was chosen as cut off for registration of desired effect.

Botulinum toxin effect & adverse effect

One unit of Ona-botulinumtoxin-A is not bioequivalent to one unit of Abo-botulinumtoxin-A. The ratio- Ona-botulinumtoxin-A: Abo-botulinumtoxin-A varies between 1:3 and 1:6 [14]. An earlier double-blinded study showed that the conversion ratio of Ona-botulinumtoxin-A and Abo-botulinumtoxin-A was 1:3 [14]. Abo-botulinumtoxin-A has been shown to have a doserelated significant longer duration of the effect rather than Onabotulinumtoxin- A, with a ratio 1:4 (Ona-botulinumtoxin-A: Abobotulinumtoxin- A, p-value= 0,02) [15]. Similar to former reports 12, this report have shown that the effect on dystonia, stabilizes after a period of treatments when changing between different toxin doses. In the present study the toxin doses were stabilized when the patients felt an effect of at least 90% measured on a VAS-score (0-100%) minimum at 4 continuous consultations.

Experimental results have shown that Abo-botulinumtoxin-A diffuses faster than Ona-botulinumtoxin-A which was explained by Abo-botulinumtoxin-A´s lighter molecular weight; Abobotulinumtoxin- A 3-400 kDa vs. Ona-botulinumtoxin-A 900kDa [16], and therefore the side effects in Abo-botulinumtoxin-A compared to Ona-botulinumtoxin-A was assumed due to a higher diffusion rate [17-19]. Other studies stated that botulinum toxin products dissociate under physiological conditions, and therefore the time of diffusion is not related to the toxin size [20]. In a study using Abo- and Ona-botulinumtoxin-A in the same patient with palmar hyperhidrosis, the patient was treated with Ona-botulinumtoxin-A in one palm, and Abo-botulinumtoxin-A in the other palm at the same session for 8 months. The patientswere their own control- like in the present study. The conclusion of that study was that the efficacy and safety of treating with Ona-botulinumtoxin-A and Abo-botulinumtoxin-A was by using the toxins in the conversion ratio of 1: 2.5 [21] which is similar to our conclusion. It has also been shown that conversion ratios of 1:3 or lower could be appropriate for the treatment of spasticity, cervical dystonia, hemifacial spasm, and blepharospasm 22. In the present study we found the conversion ratio of cervical dystonia to be 1:2, 56 which is similar to the former findings [21, 22].

The repeated administration and documentation of the usage of toxin doses (every 3rd month) at the movement disorder clinic reduced the information and selection bias. Due to the long follow-up period with a positive outcome and rare expected side effects, it was found to be effective to use a conversion ratio of 1: 2,56 (Ona-BoNT-A : Abo-BoNT-A) for botulinum toxin-A. The present study did not exclude any patients if they had confounders or comorbidities in behalf of that each patient was his/her own control in this cross-over design. The study design intended to prevent informational bias when evaluating the effect shortly after the toxin injections. To prevent selection and treatment variation bias the use of data was from patients who have been stabilized first with either Ona- or Abo-botulinumtoxin-A treatment for at least a year before crossing over to treatment with the other BoNT-A.

Conclusion

Considering the positive treatment effect, and the long followup period, we concluded that it is safe and clinically useful to use a conversion ratio at 1: 2,56 based on a patient assessment when changing treatment in between Ona- and Abo-botulinumtoxin-A for cervical dystonia. We consider the conversion ratios in our study applicable in other settings as well thus the effect of the botulinum toxin treatments was evaluated on a VAS-score (each patient is his/her own control) in this long follow-up study on dystonic out-patients.

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Congenital lens dysfunction as a new, undiagnosed cause of decreased visual acuity based on observation over a period of 3 years- Juniper Publishers

 

Ophthalmology- Juniper Publishers

Abstract

Two groups of patients with diagnosed myopia and astigmatism underwent surgery to have their natural lens removed. The reason of the study was to answer a question if, and how a different level of higher order aberration generated by crystalline lenes, devoid of any visible pathologies can influence visual acuity and quality of vision. A first, examining group, which included 15 patients (29 eyes), had lens removal because of diagnosed lens dysfunction and deteriorated visual acuity to far distances. Second, the control group included 20 patients (31 eyes) with normal visual acuity who had lens removal in the process of refractive lens exchange. The level of higher order aberration generated by the lens examined preoperatively was abnormally higher in examining group as compared with control group. Visual acuity to far distances, measured in examining group was preoperatively deteriorated (mean values = 0.6 logMar) and improved postoperatively (mean values = 0.3 logMar), statistically significantly in contrast to the group undergoing refractive lens exchange, where visual acuity pre and postoperatively comparable.

Background: This article tries to prove that one of the reasons for deterioration of visual acuity, like also quality of vision lies in healthy looking crystalline lens, if it generates high values of higher order aberrations.

Aim of the study: To assess how higher order aberrations, generated by the patient’s healthy-looking lens can influence visual acuity and quality of vision.

Methods: Two groups of patients underwent surgery to have their natural lens removed in the process of refractive lens exchange and congenital lens dysfunction. Congenital lens dysfunction is so far from an undiagnosed cause of deterioration of quality of vision and decreased visual acuity to far distances.

Results: Statistically significant differences were obtained in both preoperative values of higher-order aberration generated by the lens as well as preoperative and postoperative values of visual acuity to far distances. Visual acuity in the group with congenital lens dysfunction improved statistically significantly in contrast to the group undergoing refractive lens exchange.

Conclusions: Lack of visible cause of visual acuity deterioration be an impulse to extend diagnostics to include tests for higher order aberration, generated by the lens.

Keywords: Higher Order Aberrations; Lens Dysfunction; Low Vision; Crystalline Lens Removal; Itrace; Refractive Lens Exchange

Abbreviations: BCVA: Best Corrected Visual Acuity; RE: Right Eye; CLD: Congenital Lens Dysfunction; HOAs: Higher-Order Aberrations; LOAs: Lower-Order Aberrations; RLE: Refractive Lens Exchange

Introduction

The term “Congenital Lens Dysfunction” (CLD) was introduced by the author of this article to identify the cause of the impairment of visual function in terms of quality of vision and visual acuity to far distances. The underlying pathology is an abnormal lens structure that generates higher-order aberrations (HOAs). A very important element of the diagnosis is the absence of any visible pathologies that could be seen during biomicroscopic examination of the lens. This pathology was discovered thanks to the careful analysis of the test results obtained using the iTraceTM analyzer. This versatile device combining the functions of an aberrometer, and corneal topography allows, among others, for the separate analysis of HOAs generated by the cornea and those generated by the eye lens (Figure 1a, b). The term “Congenital Lens Dysfunction” was first described in the article “Usefulness of iTraceTM in Diagnosing Unclear Cases of the Deterioration in Visual Acuity. Congenital Lens Dysfunction as a New Disease Entity. Preliminary Reports” published in December 2020 [1]. Since then, the author’s view of congenital lens dysfunction has been slightly modified.

The main determinant of the diagnosis of CLD are high values of HOAs generated by the lens, with no obvious structural pathologies. The patients do not have cataracts, lenticonus, or a spherical lens. The patients also do not have any other pathologies, generated by other structures of the eye, cornea, optic nerve, retina. Using the word “congenital”, the author wanted to emphasize that this new term refers to a condition other than the condition of the lens known as “lens dysfunction”, which was introduced to understand the changes that occur in a lens which is undergoing opacification after the age of 40.

Despite the lack of visible pathologies, in most of cases a dysfunctional lens generates large, abnormally high HOA values, which translates into a reduction in the quality of vision and visual acuity to far distances, while maintaining correct vision to near distances. Other abnormalities, the presence of which is necessary in order to make the above diagnosis, include: poor quality of vision from childhood (patient’s medical history), presence of high or moderate myopia with accompanying astigmatism, however myopia is of a mixed, refractive-axial nature. The presence of pathology in the remaining eye structures, i.e., cornea, retina or optic nerve, does not exclude the presence of CLD, but it significantly influences correct diagnosis. Low values of HOAs generated by the cornea greatly facilitate proper diagnosis.

So far, generation of HOAs in the eye optical system has been considered only in the context of evaluation of corneal function, mainly in the processes of qualification to refractive surgery [2,3]. As a reminder, aberrations are divided into lower-order (LOA) and higher-order (HOA) aberrations. LOAs, which account for 85% of all aberrations generated by the optical system of the eye, include commonly known eye defects, including myopia, hyperopia, and regular astigmatism. These aberrations can be easily corrected using glasses or contact lenses [4].

HOAs include, among others, spherical aberration, trefoil, coma, tetrafoil, secondary astigmatism. They are most often written in the form of Zernike polynomials. The existence of HOAs in the optic system of the eye can cause blurry vision, diplopia, decreased contrast, dysphotopsia such as ‘glare’, ‘starbursts’ and ‘halo’, and blurred vision at night. These aberrations have a negative impact on vision, in eyes with a wide pupil, and therefore also in scotopic conditions [5]. The normal ranges of HOA generated by the cornea, depends on the pupil size and are between 0.046-0.338 µm (4mm) and 0.121-0.740 µm (6mm) [6]. The only correlation between the lens and values of HOA were observed in progressive nuclear cataract and concerns spherical aberration [7]. During a 3-year follow up, 59 patients aged 8 to 47, who met the criteria for the diagnosis of “congenital lens dysfunction”, were admitted to the Silesian Eye Treatment Centre (Figure 2a, b). In this group, 15 patients (23 eyes) underwent surgery to remove a dysfunctional lens.

Objective

The aim of the study is to prove the correlation between abnormally high values of HOA generated by the lens, as the only one reason of deterioration of visual acuity, examined preoperatively to far distances, like also correlation between high values of HOA and poor visual quality. A secondary aim is to assess if there is a correlation between normal visual acuity to far distances and low values of HOA, generated by the lens.

Material

Retrospective, comparative analysis of values of HOAs, visual acuity and quality of vision, obtained in two groups of patients. First, the examined group included patients with diagnosed abnormality-congenital lens dysfunction (CLD), second, control group included patients, who were qualified to refractive lens exchange (RLE). The only one abnormality observed in examined group were high values of HOA generated by the lens. 33 people (54 eyes) underwent surgery to remove their natural lens, followed by implantation of an artificial lens into the capsule. 15 patients (23 eyes) formed the examined group and were qualified for surgery to remove the lens due to its dysfunction. The second control group consisted of 20 patients (31 eyes) who wanted to get rid of refractive errors and qualified for refractive RLE (group 2). Because CLD was observed only in eyes with diagnosed myopia and astigmatism, only patients with such eye defects were included into the control group.

Preoperatively, each patient was examined using the iTraceTM analyser (Trecey® Technologies) version 6.2.0. Average values of HOAs generated by the cornea and the lens were assessed separately. In accordance with the procedure, the examination was repeated three times at short intervals (Figure 3a, b). For each patient, the values of logMar charts (far vision) and Snellen charts (near vision) obtained with best correction were assessed. Considering the subjective assessment of postoperative vision, each participant in both groups was asked about their quality of vision.

Eligibility Criteria for Surgery

Only patients who were diagnosed with myopia and astigmatism were included in the study. Examined group. Patients with abnormally high HOA generated by the lens (INTERNAL) and confirmed deterioration of visual acuity to far distances and concomitant poor quality of vision. There were no pathologies within the cornea, retina, vitreous and lens, which could have a clear impact on the decrease in visual acuity and the quality of vision. Control group Patients, which wanted to be free of eye defect with normal visual acuity too far and near distances after using best correction. Loss of accommodation properties. Another necessary element was to obtain consent for the extraction of the patient’s clear lens was the desire to improve vision in the group with CLD and to get rid of the refractive error in the group undergoing RLE. Only patients whose best corrected visual acuity (BCVA), measured to both far and near distances was normal, were qualified into the group undergoing RLE.

Exclusion Criteria

1. Abnormally high values of HOAs generated by the cornea in both groups. Patients with hyperopia and pure astigmatism.

2. Any pathologies observed in the cornea, retina, optic nerve or vitreous that clearly have a negative impact on visual acuity and the quality of vision.

3. Any visible pathologies in the structure of the lens, i.e., cataracts, lenticonus and keratoglobus, constituted an important exclusion criterion.

4. CLD suspicion in children was also a disqualifying factor, considering the possibility of further growth of the eyeball and thus a change in the scope of the refractive error.

Below is an example of a 4 yr. girl. She was diagnosed because of a very low visual acuity to far distances, observed in both eyes. Refractometry revealed high myopia and astigmatism of the right eye (RE)…….and left eye (LE)………. BCVA to the far in both eyes = 1.4 logMar. BVA without correction, in both eyes, to the near = D-0.5 (from 5cm), axial length: RE = 26.55 mm, LE= 26.28 No pathologies were found in the retina (Electroretinography), optic tract (Visual Evoked Potential), vitreous and cornea. No visible pathologies of the lens were observed. An examination using analyzer iTrace, module “Dysfunctional Lens Patient Display” revealed normal values of HOA generated by the cornea: RE=0.081, LE=0.102mm, and abnormally high HOA generated by the lens: RE=1.695mm, LE=1.695mm (figure 4a, b). Detailed types of HOA generated by above eyes are visible, using module “WF and CT summary display”.

Method

Each patient, apart from basic tests, including refractometry and intraocular pressure measurements, underwent corneal topography, endothelial cell density measurement and macular OCT. Ganglion cells thickness was examined when glaucoma was suspected. Examination of the anterior and posterior segment using direct/indirect bio microscopy, after pharmacological pupil dilation, was an obvious qualifying standard. The patient’s lens was removed using the phacoemulsification or phacoaspiration procedure. Main criteria for choosing intraocular lens have included: a value of preoperative myopia and astigmatism, a value of angle alpha, pupil size, probability to gain good postoperative level of visual acuity to far distances, patient preferences, and economic issue. Because of the above criteria, different types of intraocular artificial lenses was used, including monofocal, bifocal or multifocal toric lenses. All lenses were inserted into the lens capsule. A premium class, toric lens implantation was the surgical standard in the RLE group.

Because we still don’t know how complex structure of intraocular lens can influence the level of HOA, this parameter was not evaluated after lens exchange. Even spherical lens can generate astigmatism, postoperatively [8]. The procedures were performed by one surgeon in a private medical centre - the Silesian Eye Treatment Centre (Zory - Poland)

The following test results were subjected to comparative analysis:

1. Values of HOAs generated by the cornea and the lens (internal HOA) obtained preoperatively in both groups.

2. Values of BCVA to far distances, obtained preoperatively in both groups.

3. Values of BCVA to far distances, obtained before and after surgery in the CLD group.

4. Values of BCVA to far distances, obtained preoperatively and postoperatively in the group undergoing RLE.

5. Values of visual acuity to near distances obtained in both groups, preoperatively and postoperatively.

Additionally, the above results were assessed for the correlation between the values of HOAs generated by the lens and the preoperative values of BCVA to far distances obtained in both groups. In order to assess subjective changes in vision, each patient was asked about changes in the quality of vision and visual acuity to far distances obtained in the postoperative period.

Statistical Analysis

When developing statistical research, the correlation coefficient was examined, then it was checked whether this coefficient is statistically significant. When analyzing the statistical research, the correlation coefficient was considered. At a later stage, it was checked whether this coefficient was statistically significant.

An Information

We haven't asked for approval our institution's ethics committee for this study. Why? Because lens removal is a stable part of every surgery of cataract removal or refractive lens exchange. We haven’t changed the way of lens removal but only a reason.

Results

Analysis of the values of HOAs Obtained

The comparative analysis included averaged values of HOAs generated by the cornea and the lens (HOA internal) and its common value, generated in both groups, obtained in the preoperative period. These values are presented in Table 1. There were no statistically significant differences between the values of HOAs generated by the cornea in both groups. Statistically significant differences were found in the values of HOAs generated by the lens. They were very high in the CLD group. The HOA values obtained in the postoperative period were not analyzed due to the implantation of intraocular lenses of various structures. A range of HOAs and number of eyes where these values were achieved in preoperative period are presented in Table 2.

Visual acuity to far Distances

The mean values of BCVA to far distances obtained preoperatively and 2 months after the procedure in both groups were analyzed. These values are presented in Table 3. A particular value of BCVA, obtained preoperatively to far distances and number of eyes with such parameters are presented in Table 4. No statistical differences were observed in the values of BCVA to far distances obtained in CLE group, in the pre- and postoperative periods. In CLD group, statistically significant differences were found between pre and postoperative visual acuity, measured to far distances. BCVA to far distances improved by an average of 3 lines on logMar charts compared to preoperative visual acuity. Postoperative vision improvement was not achieved in 3 patients (3 eyes) with unilateral high myopia. Patients from CLD group who had preoperative visual acuity to far distances lower than logMar = 0.5 did not achieve full visual acuity to far distances. It is a logical consequence of the presence of an obstacle, practically from birth, which blocked the proper development of vision to far distances, as is the case with amblyopia due to disuse.

Visual Acuity and HOA values

When analyzing the obtained values, statistically significant correlations were found between

1. Normal visual acuity to far distances and low values of HOAs generated by the lens.

2. Deteriorated visual acuity to far distances and high values of HOAs generated by the lens.

3. The mean level of HOA in examining, CLD group was 2.701, as compared with control, CLE group, one the level of 0.182.

Subjective Assessment of Changes in the Quality of Vision

Patients from the CLD Group

Each of the patients undergoing lens extraction bilaterally reported an improvement in acuity and quality of vision. As previously mentioned, three patients with unilateral high myopia did not report an improvement in vision to far distances, only an improvement in the quality of vision. These people have confirmed that they have severe amblyopia.

Patients from RLE Group

Most of the patients did not notice any significant changes in BCVA and quality of vision in relation to the preoperative vision. As usual, there were a few complaints about the occurrence of negative and positive photopsia, seeing circles in the field of vision, related to the artificial lens structure.

Discussion

Lens Dysfunction. This term is synonymous with the progressive opacification of the lens and the resulting changes in vision. The presence of lens opacification, as well as pathologies of other eye structures can be easily diagnosed using appropriate diagnostic methods. Looking at literature on HOAs, no articles were found analyzing the effect of HOAs generated by the lens on the quality of vision and visual acuity. Virtually all articles focus on the descriptions of HOAs generated by the cornea. This is likely due to the lack of access to devices that can separate the aberrations generated by the lens from those generated by the cornea. The iTraceTM analyzer is one of only a few devices used in the world that allows for this type of analysis.

The first patient in whose case it was suspected that the cause of poor quality of vision and visual acuity observed in both eyes had not been described so far was a 44-year-old man. The patient underwent practically all ophthalmological diagnostic tests, and no pathologies were found within the cornea, lens, retina and vitreous body. Also, no pathologies were found in the neurological examination. The patient was diagnosed with myopia accompanied by astigmatism. Despite the use of best correction (right eye -5.0Dsph/-4.25Dcyl, left eye -8.62 Dsph/-5.5Dcyl), visual acuity to far distances did not exceed the value of 0.7 (logMar), with full acuity maintained in vision to near distances (D-0.5 on Snellen charts). Refractometry showed different, smaller values in terms of the size and axis of corneal astigmatism. The axial length of the eyeball indicated that we are dealing with mixed, refractive-axial myopia.

Examination of the eye using the iTraceTM analyzer for HOAs showed enormous values of HOAs generated only by the lens (Figure 5a, b). The patient underwent surgery in both eyes to replace the dysfunctional lens with a bifocal toric lens. There was an improvement in vision to far distances by 4 lines (logMar) and a significant improvement in the quality of vision. The visual acuity measurement repeated after 14 months gave an improvement of one line to far distances. The patient pointed out that the poor quality of vision was noticeable since an early age and that moderate myopia and astigmatism were diagnosed when he was 6.Poor quality of vision since a young age was the main element of vision that patients paid attention to after the extraction of a dysfunctional lens.

The results showed that visual acuity to far distances achieved in the CLD group improved statistically significantly but still has not reached normal values in some patients. Such a situation was observed when preoperative visual acuity to far distances was low and accompanied to abnormally high values of HOA, generated by the lens. This seems logical as the cause of poor vision likely occurred at birth or in early childhood, so vision could not develop properly. That is why the author called this yet unstudied or undescribed pathology ‘Congenital Lens Dysfunction’. There were some patients in the examining group, whose values of BCVA, examined to far distances, were between 0.3 and 0.2 (logMar), and who gained normal visual acuity postoperatively. HOA generated by those lenses, were only slightly elevated (about 400-500m).

A statistically significant correlation between high values of HOAs generated by the lens and abnormal values of visual acuity to far distances was found in the study group despite the absence of any visible pathology within the lens of the eye. Therefore, the question is whether the patient’s natural lens, which does not show any pathologies during ophthalmological examinations, can generate large, abnormal HOA values? The answer is YES, as is the case with the cornea. When evaluating the cornea in bio microscopy, in most cases we cannot know what HOA values it may generate. It is not uncommon that when abnormal visual acuity values are observed and there are no obvious reasons for this, doctors try to match the cause to the diagnosis. This results, among others, in indicating myopia with accompanying astigmatism as the cause of poor vision. As the results of this study show, this is not a good course of action.

Conclusions

Diagnosing poor visual acuity to far distances with good visual acuity to near distances and no visible pathologies within the structures of the eyeball that may cause poor vision, and the presence of moderate and severe myopia with accompanying astigmatism requires the extension of diagnostics to include a test assessing the values of HOA generated by the lens. This abnormal condition may be a consequence of congenial lens dysfunction, a pathology not described so far, the only manifestation of which is the generation of high values of HOA by the natural lens. In the diagnosis of this disease, it is necessary to use a device that allows for the differentiation between higher-order aberrations generated by the cornea and the lens. Such a device is the iTraceTM analyzer.

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Use of Aqueous Extract and Essential Oil of Citrus Aurantifolia Leaves in the Protection of Vegetables- Juniper Publishers

 

Nutrition and Food Science- Juniper Publishers

Summary

Our study is devoted to the valorization of the essential oil and the aqueous extract of Citrus aurantifolia leaves as biopesticides. The extraction of oil from the leaves was produced by hydrodistillation. The aqueous extract of the leaves was obtained by maceration. The insecticidal activity of the essential oil and the aqueous extract of the leaves of the plant was tested by spraying on two plots containing 10 Ndrowa eggplant plants. (Solanum aethiopicumm gilo) each. Leaf oil extraction yields 1.02%. On the plants sprayed with essential oil and aqueous extract of lemon tree leaves, it was observed a very significant reduction in insect pests of eggplant crops (less than 13% and 2% respectively for plots B and C). The havoc on the parties respectively with the aqueous extracts and the essential oil of the leaves of the lemon tree. The damage to plants in the treated plots was 13% and 3% for plots B and plots C respectively. Regarding the fruit conditions of Ndrowa eggplants, the frequencies of good fruits were 96%, 87% and 75% respectively for plots A, B and C. Regarding yield, plots treated with essential oil (C) and the aqueous extract (B) of lemon leaves were respectively 44% and 38% compared to 18% for the control plot (A). These oils are therefore better agents for protecting and preserving vegetables and fruits. Further study would be necessary to determine effective doses by working on a large population of insects and eggplant plants.

Keywords:Essential oil, Ndrowa eggplant, Citrus aurantifolia, Hydrodistillation, Insect, Solanum Aethiopicumm gilo

Introduction

Agriculture is one of the main sectors of activity which contributes to the socio-economic development of populations (more than 52%) in Africa [1]. Côte d’Ivoire, a country in West Africa, is an agricultural country. Its economy is mainly based on agriculture. Alongside cash crops, food crops including market garden products occupy an important place in the daily diet of populations [2,3,4]. Market gardening plays a key role in most nutrition and poverty reduction programs, fight against poverty and contribute significantly to family income [5,6]. However, the cultivation of food crops is experiencing increasing difficulties which are affecting its level of production. These include diseases and parasites (insects, fungi, viruses) which affect yield [7,8,9]. The fight against crop pests until now has been carried out using chemicals from plants of different crops [10,11]. Unfortunately, the use of pesticides in agriculture is not without consequences. The environment can be contaminated by these substances [12]. They lead to the destruction of useful species and constitute a major risk of human and animal poisoning [13,14]. Today, chemical pesticides which are undeniably effective reveal their limits through perverse effects on the ecosystem, fauna, flora [15,16]. Furthermore, the handling of chemicals by populations without any prior training are factors that expose not only the health of the consumer but also that of the producer [15]. It is therefore necessary to seek alternatives to the use of synthetic products [17]. The use of pesticidal plants is likely to significantly reduce pests and the need for synthetic pesticides [18]. Indeed, many plants are known and used for their biocidal activities (toxic, repellent, anti-feedant) against a wide range of pests. They can be used in the form of plant extracts for foliar protection [19]. Essential oils or whole plants are also used in stored food attics [20].

It is for this reason that in Ivory Coast, like many countries, studies are being carried out to find alternatives to chemical pesticides. Our study is part of the valorization of natural substances in the treatment of agricultural products against parasites harmful to market gardening crops.

The main objective is to bring food crop producers in rural areas to the use of biopesticides as alternatives to chemicals in crop pest control. It is with this in mind that our research aims to contribute to the management of pest parasites in eggplant crops by promoting the leaves of Citrus aurantifolia, a plant resource available in all rural areas of Côte d’Ivoire. This specifically involves validating the effectiveness of the aqueous extract and essential oil of Citrus aurantifolia leaves on the main pest parasites encountered on eggplant cultivation and evaluating the effect of the extracts on eggplant yield.

Materials and Methods

Study site

The test was conducted in Yamoussoukro (Lakes Region), located between 6°15-7°35 N and 4°40 and 5°40 W and 95 m altitude. The soil of the experimental plot is ferrallitic and has a sandy texture. It is highly desaturated, poor in exchangeable bases, particularly phosphorus, and comes from tertiary sands [7]. The soil is a ferralitic, gravelly and gravelly soil, more or less deep, rejuvenated, clayey-sandy (Ekou and Djidji, 1997). The climate is the Baoulean climate and straddles the pre-forest savannah and the rainforest. The terrain is generally very uneven. The distribution of rainfall is variable and is between 900 and 1100 mm 3. The average temperature is 26°C [21]. The locality has an equatorial climate with two rainy seasons (March to July and September to October) and two dry seasons (November to March and July to September). This hot and humid climate is conducive to the proliferation of fungal diseases and insect pests of vegetable plants.

Cultivation practices

Ndrowa seeds (Solanum aethiopicumm gilo) were germinated in a nursery on a small plot of 2 m² after plowing the soil. After sowing, the plot was regularly watered. After 40 days in the nursery, the plants were transplanted into three different plots of 25 m² each separated by 100 meters. To do this, the plots were cleared, plowed and watered. During this operation, the soil was enriched with a mineral fertilizer based on NPKs, at a rate of 1 g/30 m2 [22] and disinfected with the different solutions using a 2 L manual pressure sprayer. After transplanting, the plot was regularly watered every morning during the short dry season from July to September. In each plot, 10 eggplant plants (plants are approximately 15 cm high with at least three leaves) were transplanted 0.5 m × 1 m apart.

The transplants were made on July 20, 2021. A week later, the transplanting of the plants, fertilizer was again brought to the different plots. Herbs were removed throughout the experiment. From sowing to the end of observations lasted 4 months including 3 months, one week of flowering and 3 weeks of fruit harvest.

Observations and measurements

In each plot, observations focused on the following parameters: sensitivity to bacterial wilt, the level of attack on the plants, namely attacks on leaves, buds and fruits, the presence of insects, caterpillars…., the total number of fruits harvested, the average weight of the fruit.

The vegetative development of the plants was noted visually on some parameters: Susceptibility to bacterial wilt was assessed by weekly counting of all withered plants from the period of transplanting the plants until the end of the observation. The cumulative rate of wilted plants per week per plot was calculated.

To assess the damage caused by pests, a weekly count of all attacked plants (plants, leaves, buds and fruits) was carried out from the appearance of the attacks. Fruit attacks concerned fruit bores, attacks on leaves and buds concerned shredding and rolling. The cumulative rate of attacked games has been determined. The number of fruits per plant as well as the average weight of the fruit were measured on a scale. Observations relating to the number of insects were carried out during three periods (one week after the second treatment, during the flowering period and during the harvest period). The count is carried out for one week in each period. Data on pests were taken in the mornings between 6:30 a.m. and 9:30 a.m. for three days at different periods (P1, P2, P3) (Fauquet et al., 1987).

Preparation of biopesticide products

Citrus leaves aurantifolia were recovered from citrus trees aurantifolia present in the villages of Yamoussoukro. The aqueous extract was obtained by maceration of 100 g of dried leaf powder of citrus aurantifolia in one liter of water by maceration. Thus, the collected and dried leaves were ground to obtain a fine powder, then this ground material was soaked in distilled water for 24 hours. Finally, this ground material was filtered to obtain aqueous extracts. As for the essential oil of lemon leaves, it was obtained by hydrodistillation in an abininc from the fresh leaves of citrus aurantifolia.

For each of the cultivation plots, eight treatments based on plant extracts and essential oils were compared to the untreated control. Three universal manual pressure sprayers, brand DCRAFT, with a capacity of 2 liters, were used. One was used to apply the essential oil of citrus aurantifolia at a rate of 3 ml/l of water to the plants in plot C, the second to apply aqueous extracts of citrus aurantifolia leaves at a rate of 100 g /l of water on the plants of plot B. The third to be used for the application of liquid soap water on plot A. 1 liter of water was added to each mixture then 10 ml of liquid soap was added respectively to the different mixtures of leaves and essential oil of lemon tree leaves allowing them to attach to the leaves, stems, buds and fruits of the plants. So that the treatment is homogeneous and with the aim of reaching a large population of pests. All parts of the plant including leaves, buds, twigs, branches and fruits were sprayed (Bhyan et al., 2007). Furthermore, the jets were oriented so as to cover the lower and upper surfaces of the leaves of each plant, also targeting the underside of the leaves where pests tend to hide. Treatments began on crops just before transplanting, then every week after transplanting, until 14 days before the first harvest.

Data analysis

Data entered into the Microsoft Excel spreadsheet. Graphical representation and data processing were carried out using Excel software. Data were analyzed with Graph Pad Prism 8.0 software. The differences between the means were determined using the Newman- Keuls test at the 5% threshold.

Results

Plant-destroying parasites identified on the plots

The results of the parasites encountered are presented by the figures (Figure 1/A, B, C, D, E, F, G, H). The pests encountered in the different plots are beetles, jassid beetles, caterpillars, whiteflies, orthoptera and aphids (Figure 1). The whiteflies encountered are whiteflies and blackflies. The aphids encountered are the genera Aphis, Myzus , Mcrosiphum . The orthopterans encountered are grasshoppers, locusts and crickets. Beetles include beetles, weevils, ladybugs and black ground beetles. Caterpillars are the most numerous pests with a frequency of 22%. They are followed by whiteflies and beetles (19%), then aphids (17%) (Figure 1A).

The last groups of parasites encountered in the plots are orthoptera and jassids with respective frequencies of 12% and 11%. The beetles experienced considerable growth (p ˂ 0.05) from the first period p1 (15%) to the third period p3 (23%). On the other hand, aphids, whiteflies and caterpillars experienced a non-significant regression from period p1 to period p3 (p˃ 0.05) (Figure 1/C,D,E,F,G). Regarding the presence of parasites on each of the plots, on plot A, which is the control plot, the different parasites were strongly encountered during the three periods with frequencies very significantly higher (p ˂ 0.0001) than those of plots B and C treated respectively with the aqueous extract of the leaves of C. aurantifolia and the essential oil of the leaves of the plant.

On plot B, the frequencies of parasites found on site were less than 13% during all periods. Orthoptera are the parasites most encountered in this plot with frequencies of 12.7%, 6.83% and 3.8% respectively at the different periods p1, p2 and p3.

As for plot C, parasite frequencies were less than 2%. Jassids and aphids were absent during the p1 period on this plot.

A : Frequency of insects encountered on the sites B : Distribution of insects according to the period C : Distribution of pucerons on the plots D : Distribution of caterpilla on the plots E : Distribution of beetles on the plots F : Distribution of whiteflies on the plots G : Distribution of orthoptera on the plots H : Distribution of jassids on the plots

Effects of aqueous extract and essential oil of Citrus aurantifolia against parasite attacks

The yield of essential oil extraction from Citrus leaves aurantifolia by hydrodistillation was 1.02%. The results of insect pest attacks on crops in the different sites are presented in Figure 2 (Figure 2/A, B, C, D). The control plot was the plot which followed a lot of attacks (p˂0.0001) during this experiment with a frequency of 87% compared to 10% and 3% respectively for plot B and plot C. The plot was significantly less attacked (p˂0.05) compared to plot C (Figure 2/A). Regarding plot A, the majority of attacks were leaf attacks with a frequency of 64%. After the leaves, come the attacks of the buds and the fruits with respective frequencies of 23% and 10%. Problems linked to eggplant plants represent the lowest attacks (Figure 2/B). In plots B and C, attacks are dominated by damage to leaves and buds. These ravages are followed by attacks on the fruits with frequencies of 17% and 8% respectively for plot B and plot C. Attacks on the feet were very rarely observed in plots B and C (4% and 2% respectively). Wilted plants were not observed in these two plots (Figure 2/C, D). Statistical analyzes revealed a strong significance between attacks on leaves and buds compared to attacks on fruits and then on eggplant plants.

A : Distribution of insect damage on plots B : Insect damage on plot A C : Insect damage on plot B D : Insect damage on plot C

Effects of aqueous extracts of leaves and essential oil of leaves of citrus aurantifolia on the yield of different plots

On control plot A, the fruits were 75% in good condition (skin and interior) compared to 87% and 96% respectively for the fruits of plots B and plot C. the analyzes showed a small significant difference (p˂ 0.05) between the good condition of the fruits of plot A and the two other plots treated with C. aurantifolia leaves (Figure 3). Statistical analyzes also showed strong significant differences (p˂0.0001) between good and bad fruits in all plots.

In terms of yield, plot C had the best yield (44%), followed by plot B with a yield of 38%. The lowest yield was observed in plot A (18%). Statistical analyzes showed a significant difference (p˂0.001) between the yield of the control plot A and the two other treated plots (plot B and C) (Figure 4).

In terms of average weight of eggplants, the values are between 98 g and 104 g. Statistical analyzes show no significant difference (p˃0.05) between the average weights of eggplants from the different plots (Figure 5).

Discussion

Plots treated with aqueous extract and essential oil of C. aurantifolia were very lightly infested by eggplant insects at all periods. Its broad spectrum of action on parasites on sites shows that it is not selective [23]. However, the essential oil has been shown to be very effective against insects on different sites during all periods. In addition, during the first period, the essential oil was very repellent against aphids and jassids (0%) [24]. These results are similar to those of Gnago et al. [25], who showed that neem seed extract behaves as a repellent. The leaves of C. aurantifolia exhibited high pesticidal activity by effectively reducing the populations of whiteflies, beetles, caterpillars, orthoptera, aphids and jassids as well as reducing the incidence and severity of pest pests. leaves, buds and fruits. This plant would therefore have repellent and anti-appetizing properties (Nevala, 2000). The leaves would therefore contain compounds that deter feeding, repellent, inhibit oviposition and growth regulatory activities against a wide variety of crop pests [26]. The aqueous extract and essential oil of lemon leaves were able to reduce the presence and activities of insects on the plots and therefore allowed a good yield, because there is a positive correlation between the incidence and severity of crop damage and the pest population at the sites [27]. This suggests that the aqueous extract and essential oil of lemon leaves can be used as a good pesticide to protect vegetable crops. Compounds from the leaves of C. Aurantifolia have regulatory effects (antibioses/ anticenoses ) on insects [28]. Similarly, Amtul [29] reported that A. indica contains compounds that act as inhibitors of the digestive enzyme alpha-amylase in beetles. Indeed, numerous studies have shown the effects of pesticidal plants on vegetable crop aggressors. Okereke et al. [2] showed that the application of aqueous extracts of Azadirachta indica on tomato plants infected by Sclerotium rolfsii Saccardo helps reduce the severity of the disease and obtain better growth of the plants. Kankam and Sowley [30] demonstrated that amending chili plants infested with A. indica induces a significant drop in nematode populations resulting in better growth of treated plants. Echereobia et al. (2010) showed that aqueous extracts of Piper guineense induced repellent activity on arthropod pests. Kambou and Guissou [31] also noted that spicy substances (Sinapis nigra, Mochiah et al. [19] showed that Allium and C. papaya extracts led to a considerable reduction in okra and eggplant pests. Bolou et al. [32] demonstrated that the essential oil of X. aethiopic fruits strongly inhibited the mycelial growth of S. rolfsii, resulting in a considerable reduction in the incidence of the disease on treated tomato plants.

The high N’drowa yields obtained in plots B and C can be explained using different factors. First, the good vegetative development linked to the low sensitivity of these plants to bacterial wilt allowed many plants to return to production. Then, the low presence of pests on the treated sites and the very reduced number of attacks on buds, leaves and fruits. However, the yield of plot A would be linked on the one hand to the ravages of plants, buds and leaves by pests. Also, it would be linked to rotting or perforation of fruits by insect pests (caterpillars, aphids) [33]. Asare-Bediako et al. (2014) showed that extracts of A. indica, C. papaya , Allium sp . , Capsicum sp . minimized the severity of whitefly damage and increased the yield of treated plots. Adesina et al., [34] showed that the use of aqueous extracts of Loncarpous cyanescens and Dalbergia lactea reduced the ravages of leaf beetles in okra cultivation. Habou et al. [35] showed that the application of Jatropha sp. on cowpea pests made it possible to reduce the abundance of thrips and bugs and the severity of their attacks, thus increasing yield.

Furthermore, the use of biopesticides is gaining ground as these plants provide alternative means of controlling crop pests, also preserve the ecosystem [36]. Natural products from plants can also increase yields with a cost/benefit ratio comparable to that of synthetic pesticides [37]. Thus, the improvement in the yield of treated plants could be due to the release of nutrients (nitrogen, phosphorus) by the leaves for significant vegetative growth and better fruit development. Also, these properties would be due to the presence of secondary metabolites such as saponins, polyesters and phenols which would influence the metabolism of the plant and allow an improvement in plant growth and yield [38]. These results are similar to those obtained by Habou et al. [39,40,41,42] who in open fields, curcas oil significantly reduced the number of cowpea pests.

Conclusion

Plant pesticides are far from quickly replacing synthetic pesticides, particularly in large crops. In market gardening, however, they can be an alternative solution and contribute to preserving the health of populations. Pesticidal plant extracts are less dangerous than synthetic pesticides due to their fairly rapid decomposition and low polluting action. They also make it possible to keep the pest population below the harmful threshold and reduce the use of synthetic pesticides used on market gardening. The aqueous extract and the essential oil of the leaves of C. aurantifolia have proven to be powerful pesticides by the considerable reduction in the presence of pests and damage on treated crop plots but also in the good yield of eggplants observed in this study. It would therefore be necessary to explore the capabilities of biopesticides (notably lemon leaves) to control pests of vegetable crops and to optimize their use. We must encourage the use of plant pesticides by producers and raise awareness about the enhanced safety of products treated with plant-based pesticides and their long-term benefits.

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