The correlation of nuclear density using the Lens Opacity Classification System III with Pentacam Scheimpflug imaging for predicting phacoemulsification parameters: A systematic review and meta-analysis

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The correlation of nuclear density using the Lens Opacity Classification System III with Pentacam Scheimpflug imaging for predicting phacoemulsification parameters: A systematic review and meta-analysis

https://doi.org/10.21203/rs.3.rs-2453302/v1

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Introduction: In this study, we systematically reviewed the literature to determine whether or not there was a correlation between lens density as measured by the Pentacam Scheimpflug System and grading score as determined by the Lens Opacities Classification System (LOCS) III in patients with age-related nuclear cataract.

Methods: From 1990 to 2022, a systematic search was conducted in Medline (Ovid, PubMed), Embase, Scopus, Web of Science, ProQuest, and The Cochrane Library. Meta-analysis was performed for all observational studies that met the inclusion criteria. To assess the quality of cross-sectional and prospective studies, the JBI Checklist was used. To calculate the effect size for nuclear color (NC) and nuclear opalescence (NO), we used R programming software. In addition, we used Influence analysis to identify outliers and created forest plots with and without the detected outliers.

Results: Among eight studies included in this systematic review, 965 patients with 1102 eyes were assessed with a mean age of 66.23 old years. The nuclear color and density were assessed in 4 and 6 studies, respectively. The odds ratio (OR) of the effect size was 0.72 with a 95% confidence interval (0.68, 0.76) for nuclear color, and the OR of the effect size was 0.94 with a 95% confidence interval (0.94, 0.95) for nuclear density both statistically significant.

Conclusion: The Pentacam technique allowed for quantitative cataract grading and may aid in phacodynamics prediction during cataract surgery. The method is useful for detecting cataracts in patients and has broad potential in the field of health examination.

Lens Opacities Classification System (LOCS) III

Pentacam Scheimpflug System

Lens density

cataract surgery.

Cataracts are the most common type of age-related eye disease, and they are the leading cause of blindness worldwide [1]. The lens expands in size as it ages, and the continued growth of lens fibers causes the nucleus to become compressed [2]. Cataract is one of the major health problems burdening many elderlies [3]. Each year, 1.2 million cataract surgeries are done in America [4]. Fortunately, reports indicate that the visual outcomes of cataract surgery are excellent, with the majority of patients achieving corrected distance visual acuity of 1.0 (20/20) or better [5]. Since the number of people undergoing cataract surgery has increased, there has been a push to perfect reliable methods of gauging lens transparency and cataract development. Cataracts can be in a variety of stages, each of which requires its own unique classification system in order to accurately describe the disease, facilitate surgical planning, and ensure consistent research results [6].

There are two main types of cataract evaluation techniques: those that are subjective and those that are objective. Although it is subjective, the Lens Opacities Classification System III (LOCS III) is widely accepted as the gold standard for rating cataract morphological characteristics and opacity [7]. There are six slit-lamp images used to assess nuclear color (NC) and nuclear opalescence (NO), five retroillumination images used to assess cortical cataract and five retroillumination images used to assess posterior subcapsular (P) cataract. The severity of cataracts is rated on a decimal scale, and the standards use a decimal scale with evenly spaced intervals [8]. Concerns about inter- and intra-observer and temporal variation in the application of this system are valid, as they are with other subjective classification approaches. As a result, a method for accurately measuring cataract density is required [9, 10].

When comparing subjective and objective measures of lens density, it's important to keep in mind that the nucleus of the lens can have varying degrees of hardness. Preoperative phacodynamics prediction relies on careful evaluation of nuclear hardness. [11]

Objective images of the structures in the anterior chamber, including an assessment of lens density, can now be obtained with the help of cutting-edge optical technologies like the Pentacam imaging device. Scheimpflug cameras, also known as Pentacams, are non-invasive diagnostic tools that take pictures of the eye's front surface at different elevations and use those pictures to create a 3D representation of the cornea, iris, lens, and anterior segment of eye. In less than two seconds, the camera can capture 25 single-slit images as it rotates from 0 degrees to 180 degrees around the eye. It is possible to use the Pentacam to objectively measure crystalline lens density. The lens density is measured by the program on a scale from 0 to 100 based on individual images (with 0 representing no cloudiness and 100 representing a completely opaque lens). The system not only evaluates the density in three dimensions for a region of interest drawn on the Scheimpflug image, but it can also determine the density at individual points and along lines. The average density, the highest density, and the standard deviation of a given region can all be determined [12].

According to the findings of the research conducted by Lim et al., the measurements of Pentacam images indicated a strong correlation with LOCS III for nuclear opalescence (NO) and nuclear color (NC) grading (P-value < 0.01), and Pentacam Images demonstrated a higher correlation than pentacam nuclear staging (PNS)[13]. Additionally, Magalhaes et al. found that the Pentacam Scheimpflug instrument provides an objective measurement of the lens nuclear density on nuclear cataracts. The Pentacam lens densitometry program (PLDP) and the PNS mean value were useful in assessing age-related nuclear cataracts up to LOCS III group 5. [14]

In order to provide helpful information prior to cataract surgery and objective measurements to suggest an optimal time for cataract surgery, many studies establish a direct correlation between the two approaches. For instance, in nuclear cataracts, the mean values of lens density provided by the Pentacam and its new software PNS were compared to the results of clinical classification of nuclear opalescence using LOCS III.

When it comes to providing clinicians with the best option and useful information prior to cataract surgery, the literature reveals a lack of systematic reviews in this area of research. We conducted a systematic review and designed the study to arrive at a methodology that is applicable across the board in the field of health examination and successful in screening patients with cataracts.

The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) [15] criteria were used to conduct this systematic review. This study's protocol was entered into the International Prospective Register of Systematic Reviews database (PROSPERO). CRD42022375616 was the registration number.

Search Strategy

A systematic search was performed by a medical librarian in Medline (Ovid, PubMed), Embase, Scopus, Web of Science, ProQuest, and The Cochrane Library. In addition, the Iranian databases, including IranDOC, Magiran, and Scientific Information Database (SID) databases, were searched for Persian language studies from 1990 to 2022. The search strategy included a combination of Mesh, EMTREE, and free keywords such as Cataract, Lens Opacity, Lens Opacity Classification System III, LOCS 3, and Pentacam densitometry. The full Search strategy in each database is shown in Appendix 1.

Relevant sources were manually searched in selected studies. Gray literature and studies presented at conferences were also searched. Correspondence was made with people who worked in the field of study to obtain information about published and unpublished studies.

The PICO (population, interventions, comparisons, outcomes) of systematic reviews elements were as follows: Population: Cataract, Intervention: Densitometry, Comparisons: Lens Opacity Classification System III, Outcome: Grading or staging of cataract.

Eligibility Criteria

All prospective and cross-sectional studies in English from 1990 to 2022 that evaluated lens density were included in the study. Studies with participants with cataracts, mostly nuclear cataracts, underwent classification of LOC III or other grading and staging of cataracts and also were examined by Scheimpflug devices such as pentacam for comparison group entered the study. The main outcomes measured in these two groups were nuclear color and density and all its equivalents.

Articles of low-quality republished articles, laboratory, and animal studies, conference abstracts, editorials, review articles, studies with incomplete information, studies with inappropriate design, and studies with inappropriate outcomes were excluded.

Data Extraction

The articles were initially extracted using the keywords from the aforementioned databases, and then the subject expert selected them in a 3-step process. The articles had the journal name, publication year, and authors' names blacked out to reduce the Reviewers' bias. First, we looked at the titles of all the articles we reviewed, weeding out anything that didn't fit with the goals of the study. The following step involved reading both the abstracts and full texts of the articles to determine which ones were relevant. Two reviewers independently assessed the potential for bias in the studies that were included, and any disagreements were brought before a third reviewer. Table 1 displays the results of the data extraction.

Table 1

charactristics of included studies
Row	Author et al. (year)	Study design	Sample size (eye)	Sample size (person)	Age ^¥	Gender		Outcome	Result				Correlation
Row	Author et al. (year)	Study design	Sample size (eye)	Sample size (person)	Age ^¥	F	M	Outcome	Result				Correlation
1.	Magalhaes [14] (2011)	Cross-sectional	101	101	39–88 (68)	54	47	Lens density	LOCS III		PNS ^ǂ		Positive correlation for 1 to 5
									1		10.49 ± 1.76
									2		12.48 ± 2.96
									3		14.76 ± 3.46
									4		15.91 ± 4.12
									5		20.88 ± 7.76
									6		13.12 ± 1.66
8.	Jung-Sub Kim [7] (2009)	prospective observer-masked study	60	53	48–72 (61.08)	28	25	1. Lens density 2. Nuclear opacity 3. Nuclear color	NO ^ǂ = 3.38 ± 1.3 NC ^ǂ = 3.36 ± 1.31		Scheimpflug-measured lens nuclear density ^ǂ = 14.71 ± 6.12 (range 5.5 to 28.1)		Scheimpflug-measured lens nuclear density was positively correlated with the LOCS III NO and NC scores
9.	Monika Gupta [9] (2013)	Longitudinal interventional study.	100	100	44–85 (67.46)	37	63	Lens density	LOCS III		Scheimpflug measured nuclear density ^ǂ = 140.86 ± 59.73 pixel units.		Linear correlation between Scheimpflug maximum nuclear density and the LOCS III classification (P < 0.001)
									1
									2
									3
									4
									5
									6
16.	Sung-A. Lim [11] (2016)	prospective study	262	198	(70.32)	92	106	1. Age 2. Lens density	Age	LOCS III ^ǂ		PNS ^ǂ	patients > 70 years old showed a higher positive correlation coefficient (r) with Scheimpflug lens density than with LOCS III nuclear score
									51–60	2.79 ± 1.05		8.17 ± 2.00
									61–70	3.13 ± 1.13		9.07 ± 4.65
									71–80	3.21 ± 0.85		9.34 ± 3.17
									81–90	3.88 ± 1.20		14.73 ± 11.27
21.	Dilraj S. Grewal [10] (2009)	Cross-sectional	110	110	40–84 (67.1)	60	50	1. Lens density 2. Nuclear opacity 3. Nuclear color	NO^ǂ = 3.73 ± 1.49 NC ^ǂ = 3.82 ± 1.37		Scheimpflug-measured lens nuclear density ^ǂ = 63.58_20.83 (range, 36.6 − 110.5)		Correlation coefficients for both the average and nuclear lens density with LOCS III NO and NC grading,
22.	An-Peng Pan [23] (2015)	Cross-sectional	60	36	42–80 (65.8)	-	-	Lens density	LOCS III nuclear opalescence score, 3.28 ± 0.49 (range, 2.5–4.7)		Correlation ALD * PNS score = 0.492 (P-value < .001) ALD ^ǂ = 10.61 ± 1.46		Positive correlation
23.	Xpei [24] (2008)	Cross-sectional	180	138	51–86 (70.3)	78	79	1. Nuclear opacity 2. Nuclear color	LOCS III	PNS NO ^ǂ		PNS NC ^ǂ	Positive correlation
									0.1–0.9	9.7 ± 1.29		9.7 ± 1.29
									1.0–1.9	10.5 ± 1.02		10.1 ± 2.38
									2.0–2.9	14.1 ± 1.84		18.2 ±‌ 5.91
									3.0–3.9	20.7 ± 1.86		21.1 ± 6.36
									4.0–4.9	25.7 ±‌ 1.94		24.4 ± 6.46
									5.0–5.9	30.0 ± 1.98		29.41 ± 5.53
									6.0–6.9	36.5 ± 3.79		33.93 ± 4.31
31.	Hui lim [13] (2014)	Cross-sectional	229	229	34–85 (59.92)	113	116	1. Nuclear color 2. Nuclear opacity	correlation coefficient between LOCS III and PNS				Significantly positive correlations with clinically used LOCS III grading
									PNS	NO		NC
									Mean	0.7217		0.5837
									Max	0.3489		0.4241
ALD: average lens density LOCS III: Lens Opacity Classification System III NC: Nuclear color NO: Nuclear opacity PNS: Pentacam nuclear staging
^ǂMean ± sD, ^¥ Range (Mean)

Quality Of Studies

Using the JBI Critical Appraisal Checklist for cross-sectional studies [16] checklist, two authors evaluated the quality of the studies. High and medium-quality articles were selected and included in this study. Any discrepancies between these two reviewers were ironed out with the help of a third investigator.

Statistical Analysis

We used the R programming language, and the packages "meta" and "dmetar" for our meta-analysis [17]. Fisher's z-transformation of correlations was performed to obtain accurate weights for each study [18]. DerSimonian-Laird estimator was used to calculating the tau-2 values [19]. We used I² values to detect between-study heterogeneity [20]. We performed Influence analysis as proposed by Viechtbauer and Cheung to detect outliers and produced forest plots with and without the detected outliers [21]. To detect possible publication biases, we used funnel plots and Egger's test of the intercept [22]. For studies that did not report correlation coefficients, we have used Pearson's method with the data provided in the manuscripts to calculate the correlation.

Among 135 studies searched through the literature with inclusion and exclusion criteria at last, eight cross-sectional studies [7, 9–11, 13, 14, 23, 24] were selected for meta-analysis. The Flowchart of data entry studies in the systematic review is shown in Fig. 1.

In the present study, six studies were analyzed together due to the same conditions performed; two studies were reported separately. Among eight studies included in this systematic review, 965 patients with 1102 eyes were assessed which 44% were male and 56% were female. The mean age of participants was 66.23 years old.

The nuclear color was assessed in 4 studies [7, 10, 13, 24] which Fig. 2 shows the forest plot of these studies in which 579 eyes were assessed, and the OR of effect size was 0.72 with a 95% confidence interval (0.68, 0.76) with a p-value of under 0.05. The correlation OR is 0.72, which shows a positive correlation between the two groups. Unfortunately, the heterogeneity rate is high, but all the available studies were used in the analysis due to a low number of studies. The funnel plot of these studies is shown in Fig. 3.

The nuclear opacity was assessed in 6 studies [7, 9, 10, 13, 14, 24] which Fig. 4 shows the forest plot of these studies in which 780 eyes were assessed, and the OR of the effect size was 0.94 with a 95% confidence interval (0.94, 0.95) with p value 0.00. The correlation is 0.94 which shows a positive correlation between the two groups. Unfortunately, the heterogeneity rate is high, but all the available studies were used in the analysis due to a low number of studies. The funnel plot of these studies is shown in Fig. 5.

Quality Of Studies

Two authors performed the quality of the studies according to the JBI checklist for cross-sectional studies [16], and the results are accessible as supplementary digital material in Appendix 2. It is noteworthy that six studies [7, 10, 11, 13, 23, 24] did not adequately characterize confounding factors (question 5), and all included studies did not discuss how to deal with them (question 6).

The requirement to break up the nucleus during the phacoemulsification process creates additional difficulties, particularly when working with nuclei that are particularly rigid. Therefore, knowing the nuclear density is essential for accurately predicting phacoemulsification parameters and significantly lowering the risk of intraoperative complications such as posterior capsule rupture [25].

As a grading system for age-related cataracts, LOCS III has found widespread application in both clinical practice and scientific investigation [26]. There is room for error due to observer bias, and questions remain about inter- and intra-observer reliability [27]. So, to get the most accurate assessment possible before surgery, it's crucial to switch to a more objective method of measuring nuclear density. Comprehensive examination of the front of the eye, including lens densitometry, can be objectively evaluated in a single scan with the Pentacam (Oculus) without touching the cornea. [27]. Scheimpflug densitometry has been demonstrated to be an accurate method of assessing lens density, and this review analyzes the research that has compared this method to the clinical categorization LOCS III of age-related nuclear cataracts. Putting this into practice would allow for individualized cataract surgery. Furthermore, the system could be applied to research involving cataract formation or anti-cataract medications. Given its high reproducibility and level of detail about lens density, the Scheimpflug system appears to be a sensitive tool to assess temporal changes in lens density. The surgeon will be better prepared to manage ever more sclerotic nucleus if Scheimpflug grading is incorporated in to the routine operative planning in centers with adequate resources.

Pentacam imaging is quicker, easier to use, and more patient-friendly because it requires less training time. Pentacam Scheimpflug lens densitometry's high repeatability within and between observers and correlation with LOCS III scales have been confirmed by a number of studies [28].

Pentacam assessment of lens densitometry is a great objective method, but it has a few drawbacks, including providing absolute density values and being affected by external factors such as corneal opacities, insufficient pupil dilation, variations in photographic illumination, film computation, and different image analysts, despite grayscale standardization. Due to potential interference with density measurement, the blue light scan, which is the primary mode of operation for the Pentacam Scheimpflug camera, may not be as accurate as the clinical method when assessing nuclear cataracts. The new Pentacam software, PNS, provides us with more data about lens densitometry, especially when we look at the mean values, which could be useful for gauging the development of cataracts in clinical settings.

A positive correlation coefficient between both techniques has been detected in most studies. In this study, six studies have been meta-analyzed for two outcomes of nuclear color and density comparing two methods of LOCS III and Pentacam Scheimpflug. Moreover, fortunately, positive correlation has been detected for these two outcomes. Although heterogeneity was high, all the available good-quality studies were included in this systematic review.

One of the studies looked at the correlation between these two methods within age groups that were over 50 years old and found that the correlation between the two methods increases after the age of 70. The study also found that age interferes with other outcomes, such as nuclear color and density, and came to the conclusion that Scheimpflug lens densitometry may be more useful for predicting phacodynamics in nuclear cataract patients than LOCS III scores, particularly in older patients (over 70 years old) [11]. This study could not be interred to meta-analyzed, but the results were in the same direction as other studies.

In one study, researchers looked at the correlation between patients' subjective scores on the Visual Function Index-14 (VF-14), the Lens Opacities Classification System III (LOCS III), the average lens density as measured by the Pentacam Nucleus Staging system, and the objective scatter index as measured by the Optical Quality Analysis System in cases of age-related cataract. Similar results were seen in this study, which also could not be meta-analyzed with other studies. It asserts that LOCS III grading is still a cost-effective way to evaluate lens opacities, especially in early cortical cataracts that manifest on the periphery while the central cortex is relatively clear. If you want to analyze the relationship between the results of an ocular exam and the patient's complaints in an objective manner, the objective scatters index may be a helpful parameter to use. Finally, a preoperative objective cutoff for objective scatters index scores > 3.0 may be appropriate [23].

A comparison was made between the diagnostic accuracy of the Pentacam Cataract Grading Scale (PCGS) and the Lens Opacities Classification System (LOCS III) in grading pure age-related cataracts in a sample of 300 eyes. Due to the inherent inconsistency in the pentacam software and the disparate outcomes measured and assessed, we were unable to include it in our study. Even though they found only a 0.47 (P-value < 0.001) correlation between the two methods' grading scales, they concluded that LOCS III is a more cost-effective and efficient tool for evaluating lens opacities than PCGS. The use of PCGS in prenatal diagnosis [29].

The limitation of this study can be related to the fact that there was a lot of heterogeneity between the included studies. Another point that may be better to consider is the design of the studies conducted on this subject, which are mostly observational studies.

It is possible that a comparison study between Scheimpflug imaging and anterior segment optical coherence tomography (AS-OCT) is necessary to evaluate their clinical usefulness in assessing the state of the lens, aiding in the measurement of the posterior cortex and posterior capsule, and providing other anterior segment information useful before cataract surgery. Scheimpflug imaging could be incorporated into software alongside optical coherence tomography measurements to aid the surgeon in preoperative planning.

Quantitative grading of the cataract was made possible by the Pentacam method, which also has the potential to improve phacodynamics prediction during cataract surgery. The procedure is useful for screening patients for cataracts and has the potential to be used in a more broad sense within the context of the area of health evaluation. Because of this, it appears that ophthalmologists can use this procedure in the preoperative assessment of cataract surgery and so lower the chance of surgical consequences; nonetheless, it is thought that further research is required in this area.

AS-OCT: anterior segment optical coherence tomography, C: cortical cataract, LOCS: Lens Opacities Classification System, NC: nuclear color, NO: nuclear opalescence, OR: odds ratio, P: posterior subcapsular, PCGS: Pentacam Cataract Grading Scale, PICO: population-interventions-comparisons-outcomes, PLDP: Pentacam lens densitometry program, PNS: Pentacam nuclear staging, PRISMA: The Preferred Reporting Items for Systematic Reviews and Meta-analysis, PROSPERO: International prospective register of systematic reviews, SID: Scientific Information Database, VF-14:Visual Function Index-14

Ethics approval and consent to participate

The medical ethics committee of Tabriz University of medical science approved this study with ethics ID: IR.TBZMED.REC.1400.807. This research was carried out following the Declaration of Helsinki.

Consent for publication

Not applicable

Availability of data and materials

All available data are presented in this article and if more explanations are needed, contact the corresponding author.

Competing interests

No author states to have any conflicts of interest.

Funding

This study was not funded by any particular organization, company, etc.

Authors' contributions

The project was led by M.M. and F.F., who also wrote the manuscript and created the theoretical framework. E.B. and F.F. developed the study and contributed to its analysis. N.V. and A.J. searched databases, selected articles, and extracted data. F.A. and A.J. carried out the analysis and interpreted the results. With their knowledge and criticism, all of the authors contributed to the development of this study.

Acknowledgments

We thank the Research Center For Evidence-Based Medicine staff of Tabriz University of Medical Sciences for their assistance.

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No competing interests reported.

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The correlation of nuclear density using the Lens Opacity Classification System III with Pentacam Scheimpflug imaging for predicting phacoemulsification parameters: A systematic review and meta-analysis

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Abstract

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Introduction

Methods And Materials

Search Strategy

Eligibility Criteria

Data Extraction

Quality Of Studies

Statistical Analysis

Results

Quality Of Studies

Discussion

Limitations And Recommendations

Conclusion

List Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

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