Two-Year Follow-Up clinical Study of Mini WELL Extended Depth-of-Focus Intraocular Lens Implantation: Performance and Safety Evaluation

doi:10.21203/rs.3.rs-4723302/v1

Background

Cataracts can be effectively treated with intraocular lens (IOL) implantation following lens removal via phacoemulsification. The growing demand for additional correction of near and intermediate vision in the aging population has led to the development of multifocal intraocular lenses (IOLs). More recently, a novel class of intraocular lenses (IOLs), known as extended depth-of-focus (EDoF) IOLs, was introduced. The EDoF IOLs extend a single focal point over a range of distances, thereby enhancing intermediate and near performance and providing greater spectacle independence. Moreover, EDoF IOLs represent a promising solution to minimize photic phenomena and contrast sensitivity (CS) issues associated with traditional multifocal IOLs. Currently, there is a lack of long-term data on the performance and safety of EDoF lenses.

Methods

This monocentric, retrospective, observational, open-label investigation was aimed at assessing the long-term (two years) performance and safety of the EDoF Mini WELL after IOL implantation. The study included 23 male and female patients who underwent cataract surgery with the Mini WELL. Data collection included subjective refraction, defocus curve assessment, uncorrected and corrected visual acuity at all distances, binocular reading performance, contrast sensitivity (CS), Visual Function Questionnaire VF-11R, and the collection of potential adverse events during the two-year follow-up period.

Results

The results demonstrated that Mini WELL provided a long-term visual performance, safety profile, and improved reading speed. The defocus curve indicates a continuous range of vision without a significant loss in intermediate vision. A high percentage of patients maintained the clear vision outcomes, for both monocular and binocular measures, at the two-year follow-up. No adverse events (AEs) were reported.

Conclusion

The use of EDoF Mini WELL represents an interesting option for the long-term solution for visual correction of aphakia in adult patients with presbyopia.

Trial registration

The retrospective study was registered in the ClinicalTrials.gov database as NCT04801992 on March 15, 2021

cataract

extended depth-of-focus

intraocular lens

presbyopia

visual performance

safety

defocus curve

In developed countries, cataracts are readily treatable by phacoemulsification and intraocular lens (IOL) implantation. As the population in these countries continues to age, there is an increasing need for additional correction of intermediate and near vision. Consequently, a wide range of multifocal IOLs has been developed to correct presbyopia following traditional IOL implantation [1–4]. Bifocal and trifocal IOLs enhance near, intermediate, and distance vision, thereby reducing reliance on spectacles. However, their use is constrained by photic phenomena and reduced contrast sensitivity (CS). Recently, extended depth-of-focus (EDoF) IOLs [5] have been developed to increase the depth of focus, create a continuous focus rather than multiple distinct foci, and avoid the undesirable effects of multifocal IOLs. Mini WELL (SIFI S.p.A., Catania, Italy) is an aspheric progressive EDoF IOL designed for continuous vision in the range of infinity to near (40 cm) distance. This EDoF IOL comprises three optical zones: an outer monofocal zone and two zones with spherical aberrations of opposite sign, an inner zone inducing positive spherical aberrations, and an intermediate zone inducing negative spherical aberrations. The transition between the three optical zones is characterized by a gradual power shift, which supports uninterrupted continuous vision.

Currently, there are no prospective comparative studies between Mini WELL and trifocal IOLs, however data are available from in vitro evaluations. In particular, Domínguez-Vicent et al. [6] reported that Mini WELL showed a larger defocus tolerance at near distances and a better optical quality at far vision with a 4.5 mm aperture than the diffractive lenses TECNIS Symfony (Johnson & Johnson Vision, Santa Ana, CA, USA). The same author [7] evidenced that the optical quality of the Mini Well IOL was similar to that of the AT LISA tri 839MP (Carl Zeiss Meditec, AG, Jena, Germany) and Finevision (PhysIOL, Liége, Belgium) at intermediate and near vision foci for the 3.00 mm optical aperture, and it was better than the optical quality of both trifocal IOLs at distance vision when the aperture was set to 4.50 mm [7]. Several studies [8–14] have evaluated the visual performance and safety of patients implanted with Mini WELL. However, there are no published data on the long-term follow-up.

This paper presents the results of a two-year follow-up study on the safety and visual performance of EDoF IOLs Mini WELL. The patient population was derived from one of the sites involved in the previous PSM8 study [14], in which the visual performance of the Mini WELL was evaluated by a postoperative visit conducted between 30 and 60 days after surgery.

Study design

This was a retrospective, observational, single-center study carried out at the University of Bari “Aldo Moro,” one of the five sites participating in the previous PSM8 study [14]. The present study was conducted in accordance with the principles of Good Clinical Practice, Declaration of Helsinki, and Italian regulations. The study was approved by the Independent Ethics Committee of Azienda Ospedaliera Universitaria (AOU) Consorziale Policlinico di Bari on October 10, 2019. Written informed consent was obtained from all the patients. This study was registered on March 15, 2021 in the ClinicalTrials.gov database (NCT04801992).

Study population

The study included male and female patients aged ≥ 18 years who had previously been enrolled between April 8, 2014 and January 22, 2016 in the PSM8 study. These patients underwent cataract surgery or refractive lens replacement (RLE) by means of conventional phacoemulsification or femtolaser-assisted procedures (without specification of corneal incision size and position). The procedure was performed with preoperative symmetric keratometric astigmatism < 1.00 D and healthy, non-surgically treated corneas. The following exclusion criteria were applied: previous corneal surgery (e.g., pterygium, refractive surgery), eye diseases with Snellen visual acuity (VA) less than 20/32, pseudoexfoliation, abnormal pupil size and position, use of contact lenses within 30 days prior to the preoperative visit, and corneal warpage.

Data Collection, Time Points, and Study Outcomes

The baseline ophthalmic examination was performed during the preoperative visit. This included ocular refraction, optical biometry, corneal topography and asphericity, and corneal aberrometry. Quantitative and qualitative evaluation of visual performance of the Mini WELL in terms of progressive vision was conducted at 1–2 months and 24 months post-surgery (Table 1).

Table 1

Outcome measures and timing of evaluation
Outcome measures	Timing of evaluation
	Preoperative	1–2 months follow-up	24 months follow-up
Subjective refraction (sphere, cylinder, sphere equivalent)	✓	✓	✓
Defocus curve		✓ Monocular	✓ Binocular
Monocular and binocular Uncorrected Distance Visual Acuity (UDVA) and Corrected Distance Visual Acuity (CDVA)			✓
Monocular and binocular Distance Corrected Near Visual Acuity (DCNVA)		✓^a	✓
Monocular and binocular Uncorrected Intermediate Visual Acuity (UIVA) at 100 cm and 63 cm			✓
Monocular and binocular Distance Corrected Intermediate Visual Acuity (DCIVA) at 100 cm and 63 cm			✓
Monocular and binocular Uncorrected Near Visual Acuity (UNVA) at 40cm			✓
Monocular and Binocular DCNVA at 40cm			✓
Distance-corrected contrast sensitivity (CS)		✓ Monocular	✓ Binocular
Binocular reading performance		✓	✓
Halo finding		✓	✓
Visual Function Questionnaire (VF-11R)			✓
Postoperative Complications			✓
Subjective Posterior Capsule Opacification (PCO)			✓
Posterior Capsulotomy			✓
Adverse Events (AEs) including Secondary Surgical Interventions (SSIs)		✓	✓
Device Deficiencies		✓	✓
Photic Phenomena Assessment			✓
^aOnly in a subgroup of patients underwent bilateral implantation

During the follow-up period, monocular and binocular defocus curves were determined under photopic conditions through the addition of positive lenses up to + 1 D (1–2 months follow-up) or + 2.0 D (24 months follow-up), and negative lenses up to -4.0 D in half-diopter increments.

Early Treatment Diabetic Retinopathy Study charts (ETDRS) with computerized optotypes were employed to assess uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) at a distance of 4 m. Monocular and binocular visual acuity were evaluated by determining the proportion of eyes that achieved visual acuity targets between Snellen 20/20 and Snellen 20/100. The clear vision range, corresponding to Snellen 20/40 (0.30 logMAR) or better, is considered the minimum standard for safe driving in Europe [15]. However, in the 24 months long-term study on the visual performance of the Mini Well, a threshold of 20/32 Snellen (0.2 LogMAR) was considered, in accordance with the updated standard of the American Academy of Ophthalmology [16].

The monocular and binocular visual acuities were evaluated in accordance with the medical practice of the involved site using the ETDRS in computerized optotypes, namely, the YANG SMART (SIFI S.p.A., Catania, Italy).

CS was performed with varying spatial frequency grids of 1.5, 3, 6, 12, and 18 cycles per degree (cpd) without glare, using the YANG SMART and CSO Vision Chart Device (CSO, Florence, Italy). Absolute values of contrast sensitivity in logarithmic units (logCS) were measured for each spatial frequency.

The reading performance of the subjects was evaluated using the Radner Reading Charts [17] at a distance of 40 cm under photopic conditions. Reading speed, expressed in words per minute (WPM), was calculated as the number of words in a sentence divided by the time in seconds required to read the sentence. Additionally, safety outcomes were evaluated. The incidence of adverse events (AEs), the occurrence of secondary surgeries due to the optical properties of the IOL, and the frequency of visual disturbances and distortions reported by participants were evaluated using the Halo and Glare Simulator [18–20].

The supplementary method provides further details regarding the technique used for the detection of visual disturbances and distortions.

Statistical analysis

Owing to the descriptive nature of this study, no a priori sample size estimates or statistical hypotheses were planned. Data were reported as 95% confidence intervals (CIs) to provide a range of estimates based on a limited number of cases. Statistical methods employed descriptive analyses, with mean and standard deviation calculated for continuous variables and frequency and percentage calculated for discrete variables. The analysis was conducted using SAS 9.2 (SAS Institute Inc., Cary, NC, USA).

Visual Performance

This study included 23 patients (11 men and 12 women; 46 eyes) who underwent EDoF IOL Mini WELL implantation. The mean age of the patients was 71.57 ± 8.94 years (range: 47.00–84.00).

The observational period of the study commenced on March 1, 2014, and concluded on June 30, 2017. The average corneal keratometry prior to surgery was 43.66 D ± 1.70 D, the mean corneal asphericity (Q-value at 8 mm) was − 0.28 ± 0.12, and the mean axial length was 23.60 ± 1.00 mm. The mean photopic pupil diameter was 2.66 ± 0.36 mm, the mean scotopic pupil diameter was 4.40 ± 0.62 mm, and the mean topographic kappa angle was 0.26 ± 0.11 mm. The mean dioptric power of the implanted IOL was 20.98 ± 2.76 D (range: 15.0 D to 26.5 D). Two years after IOL implantation, the mean refractive values exhibited improvement in comparison with the values observed during the preoperative visit as well as the 1–2 months postoperative follow-up visit. This improvement has facilitated complete spectacle independence. Table 2 presents the subjective mean refraction data for the preoperative examination, the 1–2 months post-operative visit, and the 24 months post-operative follow-up visit.

Table 2

Subjective refraction at the preoperative, 1–2 months, and 2 years post-operative follow up visits. The 1–2 months visit data comes from the PSM8 study (98 subjects and 146 eyes).
Subjective refraction	Preoperative Visit (eyes N = 42)	Postoperative 1–2 months Visit (eyes N = 146)	Postoperative 2 years Visit (eyes N = 46)
Sphere (D)	0.393 ± 1.788	-0.07 ± 0.31	0.000 ± 0.350
Cylinder (D)	0.167 ± 0.447	-0.14 ± 0.40	-0.082 ± 0.619
Spherical equivalent (D)	0.476 ± 1.860	-0.13 ± 0.38	-0.041 ± 0.467

Figure 1 shows a comparison of defocus curves assessed in monocular vision at 1–2 months and binocular vision at 24-months post-operative, respectively.

Monocular and binocular defocus curves were measured using ETDRS charts at a distance of 4 meters, and visual acuity (VA) was evaluated at different simulated distances using lenses with power ranging from + 1.0 diopter (D) to -4.0 D and from + 2.0 D to -4.0 D, respectively. Both the monocular and binocular defocus curves showed a gradual decrease in VA with increasing negative defocus levels. There was no performance decline or VA gaps at the intermediate ranges, and there was no sharp drop in acuity in the near zone. The single peak "inverted V" profile of both defocus curves indicates that Mini WELL provides a continuous range of focus with VA that gradually declines as the distance from the subject changes. The range of clear vision of 0.3 logMAR or better (20/40 Snellen) from + 1.0 D to -2.0 D was achieved in monocular defocus curves. In contrast, the binocular defocus curve assessed at 24 months follow-up demonstrated a mean VA of 0.3 logMAR or better (20/40 Snellen) achieved after using − 2.5 D of defocus. These data demonstrate an improvement in visual acuity compared to the − 2.0 D at the 1–2 months follow-up, suggesting a better visual acuity at near distances.

.

VA was evaluated at two years of follow-up for both monocular and binocular vision at all distances (4 m, 100, 63, and 40 cm). The distribution of eyes that achieved 20/32 Snellen visual acuity (0.2 LogMar) is presented in Fig. 2. These results indicate that 65.20% and 100% of patients achieved monocular and binocular uncorrected distance visual acuity (UDVA), respectively, while 20/32 Snellen-corrected distance visual acuity (CDVA) was achieved in 100% of cases in both monocular and binocular vision. Mean values at 24-months follow up are reported in Table 3.

Table 3

Monocular and Binocular Uncorrected Distance Visual Acuity (UDVA) at 4m and Monocular and Binocular Corrected Distance Visual Acuity (CDVA) at 4m in the 24-months follow up visit
	N	mean	SD	median	minimum	maximum
Monocular
UDVA (logMAR)	46	0.19	0.14	0.15	0.00	0.50
CDVA (logMAR)	35	0.05	0.06	0.00	0.00	0.20
Binocular
UDVA (logMAR)	23	0.06	0.07	0.10	0.00	0.20
CDVA (logMAR)	21	0.01	0.05	0.00	-0.10	0.10

Intermediate visual acuity (VA) was tested at both 100 and 63 cm, with and without correction. Monocular and binocular uncorrected intermediate visual acuity (UIVA100) at 100 cm were achieved in 84.8% and 95.7% of patients, respectively, with similar results observed for distance-corrected intermediate visual acuity (DCIVA100). Mean values at 24-months follow up are reported in Table 4.

Table 4

Monocular and Binocular Uncorrected Intermediate Visual Acuity (UIVA) at 100 cm (High Contrast) and Monocular and Binocular Distance Corrected Intermediate Visual Acuity (DCIVA) at 100 cm (High Contrast) in the 24-months follow up visit
	N	mean	SD	median	minimum	maximum
Monocular
UIVA (logMAR)	46	0.05	0.22	0.10	-0.30	0.60
DCIVA (logMAR)	35	0.04	0.22	0.00	-0.30	0.60
Binocular
UIVA (logMAR)	23	-0.07	0.19	-0.10	-0.30	0.40
DCIVA (logMAR)	21	-0.09	0.20	-0.10	-0.30	0.40

Monocular and binocular uncorrected intermediate visual acuity at 63 cm (UIVA63) was achieved in 71.7% and 82.6% of patients, respectively, and similar results were achieved for distance-corrected intermediate visual acuity (DCIVA63). Mean values at 24-months follow up are reported in Table 5.

Table 5

Monocular and Binocular Uncorrected Intermediate Visual Acuity (UIVA) at 60 cm (High Contrast) and Monocular and Binocular Distance Corrected Intermediate Visual Acuity (DCIVA) at 60 cm (High Contrast) in the 24-months follow up visit
	N	mean	SD	median	minimum	maximum
Monocular
UIVA (logMAR)	46	0.08	0.30	0.10	-0.30	0.70
DCIVA (logMAR)	35	0.11	0.32	0.10	-0.30	0.70
Binocular
UIVA (logMAR)	23	-0.03	0.25	0.00	-0.30	0.40
DCIVA (logMAR)	21	-0.02	0.24	0.00	-0.30	0.30

Similarly, high percentages were achieved for uncorrected and corrected near visual acuity at 40 cm (UNVA40 and DCNVA40). In binocular vision, 65.2% and 52.4% of the patients demonstrated visual acuity of 20/32 Snellen. Mean values at 24-months follow up are reported in Table 6.

Table 6

Monocular and Binocular Uncorrected Near Visual Acuity (UNVA) at 40 cm (High Contrast) and Monocular and Binocular Distance Corrected Near Visual Acuity (DCNVA) at 40 cm (High Contrast) in the 24-months follow up visit
	N	mean	SD	median	minimum	maximum
Monocular
UNVA (logMAR)	46	0.17	0.39	0.25	-0.30	0.90
DCNVA (logMAR)	35	0.19	0.38	0.40	-0.30	0.80
Binocular
UIVA (logMAR)	23	0.06	0.33	0.10	-0.30	0.50
DCNVA (logMAR)	21	0.08	0.33	0.10	-0.30	0.60

These findings provide evidence that the Mini WELL exhibits favorable visual performance when evaluated over an extended period.

As shown in Fig. 3, based on the standard minimum reading speed of 80 WPM for fluent reading [21], 91.3% of the patients at the two-year follow-up could fluently read binocularly at the print size used for books (0.5 logRAD).

The binocular average CS at the two-year follow-up was consistent with the monocular CS data recorded at the 1–2 month postoperative visit in the PSM8 study. The values tended to decrease while remaining within the normal range, even at lower luminance levels (Fig. 4).

The Visual Function Questionnaire (VF-11R) was used to evaluate the degree of difficulty in performing 12 vision-dependent activities (e.g., reading and watching television). Higher scores (indicating "No" or "A little") are indicative of better visual functioning (i.e., less difficulty) and, thus, greater ability to perform the activity. Conversely, higher scores (indicating "A great deal" or "Unable to do the activity") indicate poorer visual functioning (i.e., greater difficulty) and, consequently, diminished ability to perform the activity [22].

The VF-11R revealed that the majority of patients exhibited minimal difficulties in reading small print (82.6%), reading a newspaper or a book (82.6%), reading a large-print book or a large-print newspaper or numbers on a telephone (82.6%), The patients demonstrated an ability to recognize people when they are close (82.6%), see steps, stairs, or curbs (86.9%), read traffic signs, street signs, or store signs (82.6%), and perform fine handwork such as sewing, knitting, crocheting, and carpentry (86.9%). They also exhibited the capacity to write checks or fill out forms (78.2%) and to participate in sports such as bowling, handball, tennis, and golf (82.7%). The data also indicates that 78.2% of respondents engage in leisure activities such as playing games like bingo, dominos, card games, and mah-jong, while 78.3% participate in sports like bowling, handball, tennis, and golf. Finally, 78.2% of respondents engage in leisure activities such as cooking, while 78.3% watch television. These findings are presented in Table 7.

Table 7

Percentage of answers for each item in the Visual Function Questionnaire VF-11R (VF-11R) at 2 years. The patients indicated whether they experienced difficulties, even with glasses, in performing the following 12 tasks.
	Question	Answer	%
Do you have difficulties, even with glasses…	1. Reading small print, such as labels on medicine bottles, a telephone book, food	No	56.52
		A little	26.09
		A moderate amount	17.39
		A great deal	0.00
		Unable to do the activity	0.00
	2. Reading a newspaper or a book	No	69.57
		A little	13.04
		A moderate amount	17.39
		A great deal	0.00
		Unable to do the activity	0.00
	3. Reading a large-print book or a large-print newspaper or numbers on a telephone	No	73.91
		A little	8.70
		A moderate amount	8.70
		A great deal	8.70
		Unable to do the activity	0.00
	4. Recognizing people when they are close to you	No	73.91
		A little	8.70
		A moderate amount	4.35
		A great deal	13.04
		Unable to do the activity	0.00
	5. Seeing steps, stairs or curbs	No	73.91
		A little	13.04
		A moderate amount	8.70
		A great deal	4.35
		Unable to do the activity	0.00
	6. Reading traffic signs, street signs, or store signs	No	73.91
		A little	8.70
		A moderate amount	17.39
		A great deal	0.00
		Unable to do the activity	0.00
	7. Doing fine handwork like sewing, knitting, crocheting, carpentry	No	56.52
		A little	30.43
		A moderate amount	8.70
		A great deal	4.35
		Unable to do the activity	0.00
	8. Writing checks or filling out forms	No	65.22
		A little	13.04
		A moderate amount	13.04
		A great deal	8.70
		Unable to do the activity	0.00
	9. Playing games such as bingo, dominos, card games, mah-jong	No	73.91
		A little	4.35
		A moderate amount	8.70
		A great deal	13.04
		Unable to do the activity	0.00
	10. Taking part in sports like bowling, handball, tennis, golf	No	78.26
		A little	4.35
		A moderate amount	13.04
		A great deal	0.00
		Unable to do the activity	4.35
	11. Cooking	No	69.57
		A little	8.70
		A moderate amount	17.39
		A great deal	4.35
		Unable to do the activity	0.00
	12. Watching television	No	69.57
		A little	8.70
		A moderate amount	21.74
		A great deal	0.00
		Unable to do the activity	0.00

At 2 years the total average score was 86.5 ± 23.1, with the highest mean score reported for “reading traffic signs, street signs, or store signs” (89.1 ± 19.7) and “seeing steps, stairs or curbs” (89.1 ± 21.1) questions and the lowest mean score (83.7 ± 25.7) reported for “writing checks or filling out forms” (Table 8).

Table 8

Mean and standard deviation (SD) score for each question of the VF-11R at 2 years. The mean score is based on the following 0-100 scale: 0 (unable to do the activity), 25 (a great deal), 50 (a moderate amount), 75 (a little), and 100 (no).
	Question	Mean	SD
Do you have difficulties, even with glasses…	1. Reading small print, such as labels on medicine bottles, a telephone book, food	84.78	19.57
	2. Reading a newspaper or a book	88.04	19.76
	3. Reading a large-print book or a large-print newspaper or numbers on a telephone	86.96	24.85
	4. Recognizing people when they are close to you	85.87	27.00
	5. Seeing steps, stairs or curbs	89.13	21.09
	6. Reading traffic signs, street signs, or store signs	89.13	19.69
	7. Doing fine handwork like sewing, knitting, crocheting, carpentry	84.78	20.97
	8. Writing checks or filling out forms	83.70	25.68
	9. Playing games such as bingo, dominos, card games, mah-jong	84.78	27.94
	10. Taking part in sports like bowling, handball, tennis, golf	88.04	25.97
	11. Cooking	85.87	23.63
	12. Watching television	86.96	21.15
	Total Avarage Score	86.50

Safety

No adverse events (AEs), postoperative complications, subjective posterior capsule opacification, or posterior capsulotomy procedures were reported during the two-year follow-up period. The assessment of photic phenomena, presented in Fig. 5, revealed a notable difference in the percentage of subjects who reported experiencing glare and halo versus those who did not report any visual disturbance (with a chi-square test for proportion result showing a p-value of < 0.0001). Among the enrolled patients, two (8.70%) reported experiencing G1 glare, while four reported halo incidents: one H1 (4.35%), two H2 (8.70%), and one H3 (4.35%).

This study assessed the long-term safety and performance of the EDoF Mini WELL in a cohort of 23 patients who underwent post-surgery visits with 2 years follow up in the AOU Policlinico of Bari, one of the sites involved in the previous PSM8 study [14]. The limitations of the study are its small sample size, descriptive and retrospective nature, and lack of a control group. To the best of our knowledge, the main strength of the trial lies in being the longest follow-up study for an EDoF-IOL. Implantation of the Mini WELL at the two-year follow-up resulted in complete independence from spectacles, satisfactory VA, and fluent reading performance (91.3% of patients were able to read fluently binocularly at bookprint size). The defocus curves under photopic conditions showed at 2 years a consistent performance in comparison to the values obtained at the 1–2 months visit in the 98 subjects (146 eyes) enrolled in the PSM8 study, which was a noteworthy finding, given that the evaluation at the two-year follow-up was conducted binocularly rather than monocularly.

With regard to the evaluation of CS at two years, there was a downward trend even at a lower luminance level, while the mean values remained within the normal limits as defined by the manufacturer in their normative database for the CS test. Furthermore, in the same cohort that was followed for the two-year follow-up period, a CS assessment was conducted approximately one to two months after IOL implantation. The data from this limited sample demonstrated optimal performance, as shown in Table 9.

Table 9

Contrast Sensitivity evaluated in the same cohort at 1–2 months (monocular in 76 eyes) and at 2 years (binocular in 46 eyes)
cpd	Monocular Contrast Sensitivity 1–2 months Visit (eyes N = 76) Mean ± SD	Binocular Contrast Sensitivity 2 years Visit (eyes N = 46) Mean ± SD
1.5	1.41 ± 0.40	1.69 ± 0.55
3	1.78 ± 0.42	1.91 ± 0.51
6	1.47 ± 0.36	1.47 ± 0.51
12	0.90 ± 0.35	0.87 ± 0.45
18	0.67 ± 0.35	0.26 ± 0.45

Furthermore, the Mini WELL exhibited in the two year follow up a favorable safety profile. The mean strength value of halos and glares (4.6%) was classified as "none" according to the strength function classification of halos and glares [29], which categorizes none (0% − 25%), mild (25% − 50%), moderate (50% − 75%), and severe (75% − 100%) levels of halos and glare. This is an important finding, as the perception of visual disturbances is a frequent issue related to IOLs, which often results in dissatisfaction and a desire for IOL removal.

The results achieved at the two-year follow-up could be explained by visual neuroadaptation to the Mini WELL implant. As shown in recent studies [23–24], the process of neuroadaptation could play a crucial role in the adaptation of visual function, particularly in improving refractive parameters and reading performance, and reducing the occurrence of visual disturbances.

The outcomes of this study align with earlier investigations of Mini WELL [8–14] and improve our knowledge of the long-term effects of IOL placement. The long-term safety of the product was confirmed by the absence of device deficiencies, product-related postoperative complications, and product-related serious AEs, including Secondary Surgical Interventions (SSIs) 2 years after surgery. The study data provide evidence for long-term follow-up of IOL Mini WELL and may be enhanced in the future with the results of additional long-term post-market investigations involving a larger patient sample size. Although this study was limited by its descriptive nature and small sample size, it provides valuable insights for future research.

The long-term performance of EDoF IOLs is a crucial aspect in the evaluation of the usefulness of these devices, which have been developed to improve the quality of vision in an aging population. This study, although preliminary and on a small number of patients, is the first to shed light on the long-term performance of Mini WELL. Interestingly, the outcomes remain stable or improve at two-year follow-up, although no formalized statistical evaluation was performed. Likewise valuable are data on the safety and absence of visual disturbances that have a major impact on the quality of vision in aging patients. Although further controlled studies are needed to confirm these data, it is possible to positively conclude on the value of the EDoF MiniWELL.

AE Adverse event

AOU Azienda Ospedaliera Universitaria

CDVA Corrected distance visual acuity

CI confidence intervals

cpd cycles per degree

CS Contrast sensitivity

D diopter

DCIVA Distance corrected intermediate visual acuity

DCNVA Distance corrected near visual acuity

EDoF Extended depth-of-focus

ETDRS Early Treatment of Diabetic Retinopathy Study

IOL Intraocular lens

logCS contrast sensitivity in logarithmic units

logMAR Logarithm of the minimal angle of resolution

logRAD Logarithm of the Reading Acuity Determination

SSI Secondary Surgical Intervention

UDVA Uncorrected distance visual acuity

UIVA Uncorrected intermediate visual acuity

UNVA Uncorrected near visual acuity

VA Visual acuity

VF-11R Visual Function questionnaire VF-11R

WPM Word per minute

Acknowledgements

Warm thanks to Salvatore Bianco MD on behalf of Opera CRO for support in medical writing and Marius Ardelean for data management and statistical analysis.

Authors' contributions

AS, DFB, AN, and GS were involved in the conception and methodology of the study. The formal analysis was performed by AS, DFB and GS. AS and GS were the responsible for investigation. AS and DFB wrote the-original draft of the manuscript. AS, LB, AN, CC, and DFB were involved in the writing and editing. The visualization was performed by LB and AN. Project supervision was carried out by AS. The responsible for project administration was CC. All authors have read and agreed to the published version of the manuscript. In addition, all authors confirm that they have agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature

Funding

Support for this clinical investigation and the medical writing assistance was funded by SIFI S.p.A., Via Ercole Patti 36, 95025, Lavinaio, Aci S. Antonio (Catania) Italy.

Data availability

The full protocol, the datasets analysed for the study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

The ethics approval was obtained from Ethics Committee of Bari on October 9^th 2019. This study was conducted in accordance with the ethical standards of the Declaration of Helsinki. Written informed consent was obtained from any subject enrolled in the study.

Consent for publication

Not applicable

Competing Interests

CC is an employee at SIFI SpA the funder of the study. DFB is employed at Opera Contract Research Organization, the CRO that monitored the study. LB is working at TIGERMED Italy the company that performed the data management of the study. AS, AN, and GS declare no conflicts of interest.

Author details

¹Eye Clinic, Hospital "SS. Annunziata", ASL Taranto, 74121 Taranto, Italy.

²Department of Medical Science, Neuroscience and Sense Organs, Eye Clinic, University of Bari, 70124 Bari, Italy.

³Innovation and Medical Science Department, SIFI SpA, 95025 Aci Sant’Antonio (CT), Italy

⁴Opera CRO, a TIGERMED company, Medical Department - 300209 Timisoara, Romania

⁵TIGERMED Italy, IT Department - 16129 Genova, Italy

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Competing interest reported. Maria Cristina Curatolo is an employee at SIFI SpA the funder of the study. Dionisio Franco Barattini is employed at Opera Contract Research Organization, the CRO that monitored the study. Luca Barattini is working at TIGERMED Italy the company that performed the data management of the study. Alessandra Sborgia, Alfredo Niro, and Giancarlo Sborgia declare no conflicts of interest.

SupplementaryMethods.docx

Two-Year Follow-Up clinical Study of Mini WELL Extended Depth-of-Focus Intraocular Lens Implantation: Performance and Safety Evaluation

Status:

Version 1

Abstract

Background

Methods

Results

Conclusion

Trial registration

Figures

Background

Methods

Study design

Study population

Data Collection, Time Points, and Study Outcomes

Statistical analysis

Results

Visual Performance

Safety

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1