- Email: [email protected]
Effect of cataract surgery on regulation of circadian rhythms
REVIEW/UPDATE
Effect of cataract surgery on regulation of circadian rhythms Jesper Høiberg Erichsen, BSc, Adam E. Brøndsted, MD, Line Kessel, MD, PhD
This review looked at the effect of cataract surgery on the regulation of circadian rhythms and compared the effect of blue light–filtering and clear intraocular lenses (IOLs) on circadian rhythms. A systematic review and metaanalysis were performed, and the level of evidence was evaluated based on the principles described in the Grading of Recommendations Assessment, Development, and Evaluation system. A literature search of PubMed, Embase, and Cochrane Library databases was performed, as well as a search for unpublished trials at the U.S. National Institutes of Health Clinical Trials web site. Trials that reported the effect of cataract surgery on circadian rhythms were included. Outcomes were the Pittsburgh Sleep Quality Index (PSQI) global score, number of poor sleepers, Epworth Sleepiness Score, sleep efficiency, and mean concentration of melatonin. Cataract surgery improved regulation of circadian rhythms measured by the PSQI questionnaire, but the clinical relevance is uncertain. There was no difference between the effect of the 2 IOL types. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2015; 41:1997–2009 Q 2015 ASCRS and ESCRS Supplemental material available at www.jcrsjournal.org.
Regulation of circadian rhythms is important for maintaining a healthy life. Dysregulation of circadian rhythms may lead to sleep disturbances and increases the risk for comorbidities such as cancer, falls, cardiovascular disease, psychiatric disorders, and cognitive impairment.1–5 Sleep disorders are often treated by sleep-inducing medications that have considerable adverse effects; eg, dependency, daytime sedation, Submitted: January 8, 2015. Final revision submitted: February 7, 2015. Accepted: March 16, 2015. From the Faculty of Health and Medical Sciences (Erichsen), University of Copenhagen, Copenhagen, Department of Ophthalmology (Erichsen, Brøndsted), Glostrup Hospital, Glostrup, and Department of Ophthalmology (Kessel), Roskilde Hospital, Roskilde, Denmark. Supported by the Velux Foundation (grant 30787), Søborg, Denmark. Lene Theil Skovgaard, Department of Biostatistics, University of Copenhagen, provided advice and guidance. Corresponding author: Jesper Høiberg Erichsen, BSc, Department of Ophthalmology, Glostrup Hospital, Nordre Ringvej 57, K-2600 Glostrup, Denmark. E-mail: [email protected]. Q 2015 ASCRS and ESCRS Published by Elsevier Inc.
vertigo, and increased risk for hip fractures.6 Excessive daytime sleepiness is correlated with increased healthrelated and social-transfer costs.7 Circadian rhythms are entrained to external cues, ambient light levels being the most important. The first step in photoentrainment is stimulation of a small subset of retinal ganglion cells (intrinsically photosensitive retinal ganglion cells [ipRGCs]), which contain the photopigment melanopsin. The ipRGCs are primarily sensitive to light in the blue spectrum, with a peak at approximately 480 nm.8–10 The circadian rhythms are entrained to the solar day by axons of the ipRGCs running through the retinohypothalamic tract to the suprachiasmatic nucleus, where the main circadian rhythm is generated and melatonin release is controlled.8,11,12 Another non-image-forming function of the ipRGCs is regulation of the pupillary light reflex by projection to the olivary pretectal nucleus.8,11 In theory, the age-related yellowing of the crystalline lens can be a factor in circadian rhythm disorders. Lens yellowing is caused by changes in interactions of the major structural proteins, the crystallins, in the lens.13,14 Over time, damaged crystallins accumulate, resulting in a translucent lens with a yellow color.15–17 Cataract is the term used when visual http://dx.doi.org/10.1016/j.jcrs.2015.09.009 0886-3350
1997
1998
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
function is impaired because of a translucent and yellow lens. Studies have shown that transmission of blue light through the lens decreases as yellowing of the lens increases, limiting the amount of blue light that reaches the retina.18,19 Because blue light is essential for photoentrainment of circadian rhythms and the physiologic aging process of the crystalline lens results in reduced transmission of blue light to the retina, the question arises whether natural yellowing of the crystalline lens and/or cataract is responsible for the development of circadian rhythm disorders. Cataract is treated by removing the cataractous lens and replacing it with an intraocular lens (IOL). The IOL is usually a clear ultraviolet (UV) light–filtering IOL or a yellow blue light–filtering IOL that also blocks UV light. The main argument for using a blue light– filtering IOL is theoretical protection from phototoxic damage due to exposure of short wavelength light.20 The blue light–filtering IOL has lower transmission of blue light to the retina than the clear UV light– filtering IOL.18,19 In theory, cataract surgery could improve photoentrainment of the circadian rhythms, but there may be a difference between the effect of the 2 IOL types on regulation of circadian rhythms. The aim of this systematic review and metaanalysis was to investigate the effect of cataract surgery on the regulation of circadian rhythms and determine whether it is better to implant a blue light–filtering or a clear IOL. The level of evidence was evaluated. MATERIALS AND METHODS The systematic literature review and metaanalysis were based on the principles described in the Grading of
Recommendations Assessment, Development, and Evaluation system.21 First, the topic of the systematic review was described using the patient, intervention, comparison, and outcome approach. The effect of yellowing of the optical media of the eye on the circadian rhythms (outcome) was investigated by comparing the situation with the natural cataractous lens in place (comparison) and the situation with the cataractous lens removed and replaced by an IOL (interventiondcataract surgery). Participants were human subjects with age-related cataract (patients). Second, the effect of transmission characteristics of the IOL on circadian rhythms (outcome) was investigated by comparing patients with age-related cataract (patients) having cataract surgery with implantation of a clear UV light–filtering IOL (comparison) and patients having implantation of a yellow blue light–filtering IOL (intervention). Randomized and nonrandomized interventional studies that reported the effect of cataract surgery on circadian rhythms were included. The studies could report on firsteye surgery, second-eye surgery, or bilateral surgery. Regulation of circadian rhythms can be measured in various ways. Actigraphy is a motion-based technology in which a device is placed on the wrist of the participant for at least 1 week. This gives an objective measure of sleep/wake time.22 An easier to administer way of measuring regulation of circadian rhythms is by evaluating sleep quality using a validated questionnaire such as the Pittsburgh Sleep Quality Index (PSQI)23 or the Epworth Sleepiness Score (ESS).24 Alternatively, regulation of circadian rhythms can be assessed by measuring melatonin concentrations in blood, saliva, or urine.25–27 Studies reporting on all types of circadian rhythm measurements were included in the review. A systematic literature search was performed in the PubMed, Embase, and Cochrane Library databases using the search profile illustrated in Figure 1. The search was performed on August 7, 2014. In PubMed and Embase, results were limited to “abstract available.” A search in U.S. National Institutes of Health Clinical Trials (www.clinicaltrials.gov) was performed to identify unpublished studies. The list of references with
Figure 1. Graphic presentation of the literature search profile (PubMed, Embase, and Cochrane Library databases).
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
abstracts was reviewed by 2 reviewers independently (J.H.E., A.E.B.), and potentially relevant studies were retrieved in full-text copies and read by all 3 reviewers before a study was included or excluded. Disagreement was resolved by discussion and consensus. The risk for bias was assessed for each included study using the Cochrane risk for bias toolA in the Review Manager softwareB (version 5.3, Revman). The assessment of risk for bias included evaluation of random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. Each item was graded as “low risk for bias,” “high risk for bias,” or “unclear risk for bias.” Disagreement was resolved through discussion and consensus. Data were extracted simultaneously by the 3 authors and entered into the Revman software program.B Some articles did not provide sufficient information about the desired data; if possible, data were later obtained from the study authors via e-mail. Continuous outcome data were analyzed using the mean differences approach and dichotomous outcome data using risk ratios. Most studies used the PSQI questionnaire23 to evaluate sleep quality. Data retrieved from the PSQI are not continuous but discrete, and the distribution is skewed. Because of this, PSQI data were transformed to a logarithmic scale if presented as a median to calculate the mean and standard deviation.28 Data presented as a mean were included without transformation based on the assumption of normally distributed changes in the mean. Measurements of melatonin levels produced genuinely continuous data. The Review Manager 5 softwareB was used to calculate estimates of overall treatment effects, and random-effects models were used to calculate pooled estimates of effects. Heterogeneity was quantified by conducting the chisquare and I2 tests in Revman 5, and substantial heterogeneity was defined in concordance with Cochrane Handbook; ie, I2 more than 50% and chi-square P value less than 0.1. During cataract surgery, the natural lens is replaced by an IOL that can have different transmission characteristics. Because of this, subgroup analysis of blue light–filtering IOLs versus clear IOLs was done. Data from different sleep scales were combined using standardized mean difference.
LITERATURE SEARCH The literature search yielded 2256 references. Titles and abstracts were reviewed and potentially relevant studies identified. In addition, 1 reference was identified by other means. After duplicates were removed, a list of 22 potentially relevant studies was produced and full-text copies were retrieved (Figure 1). Of the 22 studies, 7 were included in the analysis (Appendix 1)29–35 and the remaining 15 were excluded (Appendix e1, available at http://jcrsjournal. org).18–20,36–46,C One included study35 did not provide baseline data and could not be included in the analysis of the effect of cataract surgery; it could be included in the analysis of blue light–filtering versus clear IOLs as no baseline data were needed for that. All the included studies were nonrandomized trials29,31–35 except 1 that was semirandomized.30 No randomized controlled
1999
trials that met the inclusion criteria could be identified by the literature search. The search for unpublished studies yielded 5 results,D–H of which 3 studies were not relevant to the subject of this reviewF–H and 1 was terminated because it included too few participants.E The remaining study was ongoing but could be included in an update of this review.D Three studies implanted either blue light–filtering or clear IOLs,29,30,35 3 implanted only blue light– filtering IOLs,32–34 and 1 implanted only clear IOLs.31 Three studies had the number of poor sleepers as outcome,31–33 4 had PSQI global score as outcome,29,31–33 1 had ESS as outcome,30 and 1 had actigraphy and melatonin measures as outcomes.34 Data from actigraphy were obtained as sleep efficiency, and data from melatonin measures were obtained as the mean concentration of melatonin. The follow-up period was 1 month after surgery in 3 studies,29,30,34 2 months in another 3 studies,31–33 and 6 months in the last study.35 Risk for bias in the 7 included studies is presented in Appendix 2. Effect of Cataract Surgery The effect of cataract surgery on circadian rhythms was assessed with questionnaires, actigraphy, and the measurement of melatonin.29–34 The PSQI global score was significantly improved after cataract surgery, mean difference 0.86 (95% confidence interval [CI], 1.63 to 0.10) (P Z .03). Subanalysis of IOL type showed a significant improvement in the PSQI global score after implantation of a clear IOL, mean difference 0.47 (95% CI, 0.91 to 0.03) (P Z .04); there was no significant improvement in the PSQI global score after implantation of a blue light–filtering IOL, mean difference 1.25 (95% CI, 2.78 to 0.28) (Figure 2). There was no significant change in the number of poor sleepers (PSQI global score O5) after cataract surgery, risk ratio 0.75 (95% CI, 0.48 to 1.18) (Figure 3). The ESS did not change significantly after cataract surgery, mean difference 1.01 (95% CI, 2.60 to 0.58), and neither did sleep efficiency, mean difference 0.00 (95% CI, 3.73 to 3.73), or the mean concentration of melatonin, mean difference 4.90 (95% CI, 33.98 to 43.78) (Figure 2). Blue Light–Filtering Versus Clear Intraocular Lenses Three studies compared the effect of blue light– filtering versus clear IOLs on circadian photoentrainment.29,30,35 They used different sleep scales (PSQI and ESS), so the standardized mean difference was used to calculate a pooled estimate. No significant difference in the combined sleep scale score was found between the 2 types of IOLs, standardized mean difference 0.05 (95% CI, 0.08 to 0.18). Results are presented
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
2000
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
Figure 2. Forest plot illustrating the effect of cataract surgery on continuous circadian rhythm outcomes. Sleep efficiency is presented as percentage; concentration of melatonin is presented as pg/mL (BF Z blue light–filtering; CI Z confidence interval; cryst. Z crystalline; df Z degrees of freedom; IOL Z intraocular lens; IV Z inverse variance; Random Z random effects model).
in Figure 4. One study presented data on poor sleepers.35 No significant difference between the IOLs was found, risk ratio 1.08 (95% CI, 0.63-1.84) (Figure 5).
very low. All studies were nonrandomized, the sample size for each outcome was very small, the number of participants lost to follow-up was considerable, and heterogeneity was substantial for some outcomes.
Quality of Evidence
DISCUSSION
Results of the quality assessment of the current evidence for each outcome are presented in Table 1A and 1B. The evidence for all outcomes was rated
This review investigated the effect of cataract surgery on the regulation of circadian rhythms and whether it was better to implant a blue light–filtering IOL or a
Figure 3. Forest plot illustrating the effect of cataract surgery on the number of poor sleepers defined by a PSQI global score greater than 5 (BF Z blue light–filtering; CI Z confidence interval; cryst. Z crystalline; df Z degrees of freedom; IOL Z intraocular lens; M-H Z Mantel-Haenszel; Random Z random effects model).
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
2001
Figure 4. Forest plot comparing the effect of cataract surgery with implantation of a blue light–filtering or a clear IOL on questionnairebased sleep scale scores (standardized mean difference) (BF Z blue light–filtering; CI Z confidence interval; df Z degrees of freedom; IOL Z intraocular lens; IV Z inverse variance; Random Z random effects model).
clear IOL. The level of evidence was also assessed. A systematic review and metaanalysis of 7 nonrandomized trials was done, but no randomized trials were identified. Cataract surgery was found to significantly improve subjective sleep quality as assessed by the PSQI global score, but no significant changes were found in number of poor sleepers, ESS, sleep efficiency measured by actigraphy, or total melatonin secretion. No significant differences in the PSQI global score, ESS, or number of poor sleepers were found between the 2 types of IOLs. The results support the theory that cataract surgery improves regulation of circadian rhythms. However, no evidence favoring one IOL type over the other was found. The improving effect of cataract surgery on sleep quality indicates that cataract or yellowing of the crystalline lens may impair photoentrainment of circadian rhythms. The beneficial effect of cataract surgery on sleep quality corroborates the results in previous studies, which could not be included in this metaanalysis because of study design.37,38 Other investigators have found that lens yellowing and lenticular nucleosclerosis were associated with insomnia and degradation of sleep quality.41,42 Although we found a beneficial effect of cataract surgery, our results were not as convincing as those in a retrospective study that found sleep quality to be improved in 12.0% of men and 26.3% of women 1 month after cataract surgery.38 One study reported reduced ability of short wavelength light to suppress melatonin in older women not operated on for cataract compared with younger women,47 suggesting that
yellowing of the crystalline lens and age-related decreased pupil diameter limit the amount of blue light that reaches the retina, thus reducing melatonin suppression. In theory, cataract surgery would improve suppression of melatonin during the day by allowing more blue light to reach the retina. We found no change in the mean concentration of melatonin and were therefore unable to show a beneficial effect of cataract surgery on suppression of melatonin. However, the mean concentration may hide an improvement in the fluctuation of plasma melatonin. In healthy individuals, the concentration of melatonin in plasma is low during the day and begins to rise in the evening, peaking around 3 AM and falling back to its nadir in the morning.48 The amplitudes of these fluctuations are reduced with age,49,50 and an increase in amplitude of both peak and nadir after cataract surgery may leave the mean concentration unchanged even though the patient's circadian rhythms improve. Tanaka et al.34 estimated the maximum concentration and time of maximum concentration but found no significant effect of cataract surgery. No studies reported peak-to-trough ratios. Disagreements exist about which type of IOL should be recommended for implantation after cataract surgery.51–53 Some argue that blue light–filtering IOLs are beneficial due to a supposed protection against phototoxic retinal damage53; others argue that there is no proof of such protection52 and that the reduced transmission of blue light to the retina may attenuate photoentrainment of circadian rhythms and impair scotopic vision.20,52 Transmission spectra have shown Figure 5. Forest plot comparing the effect of cataract surgery with implantation of a blue light–filtering or a clear IOL on the number of poor sleepers (PSQI O5) (BF Z blue light–filtering; CI Z confidence interval; cryst. Z crystalline; df Z degrees of freedom; IOL Z intraocular lens; M-H Z MantelHaenszel; Random Z random effects model).
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
2002
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
Table 1A. Effect of cataract surgery on regulation of circadian rhythms in nonrandomized trials.
Outcomes
Findings (95% CI)
Poor sleepers Poor sleepers: BF IOL vs cryst lens Poor sleepers: Clear IOL vs cryst lens PSQI global score PSQI global score: BF IOL vs cryst lens PSQI global score: Clear IOL vs cryst lens ESS ESS: BF IOL vs cryst lens ESS: Clear IOL vs cryst lens Sleep efficiency (%)
Melatonin (mean concentration pg/mL)
RR 0.75 (0.48 to 1.18) in favor of cataract surgery compared with cryst lens RR 0.65 (0.31 to 1.33) in favor of BF IOL compared with cryst lens RR 1 (0.67 to 1.5) in favor of clear IOL compared with cryst lens Mean score 0.86 lower (1.63 to 0.1 lower) in favor of cataract surgery compared with cryst lens Mean score 1.25 lower (2.78 lower to 0.28 higher) in favor of BF IOL compared with cryst lens Mean score 0.47 lower (0.91 to 0.03 lower) in favor of clear IOL compared with cryst lens Mean ESS 1.01 lower (2.6 lower to 0.58 higher) after cataract surgery compared with cryst lens Mean ESS 0.8 lower (3.64 lower to 2.04 higher) in favor of BF IOL compared with cryst lens Mean ESS 1.1 lower (3.02 lower to 0.82 higher) in favor of clear IOL compared with cryst lens Mean efficiency 0 higher (3.73 lower to 3.73 higher) in favor of cataract surgery compared with cryst lens Mean concentration 4.9 higher (33.98 lower to 43.78 higher) in favor of cataract surgery compared with cryst lens
Number of Participants
Quality of Evidence
504 (3 studies)
Very low*
376 (2 studies)
Very low*
128 (1 study)
Very low*
2294 (4 studies)
Very low*,†,z
1214 (3 studies)
Very low*,†,z
1080 (2 studies)
Very low*,†,z
126 (1 study)
Very low*,x
46 (1 study)
Very low*,x
80 (1 study)
Very low*,x
24 (1 study)
Very low*,k
24 (1 study)
Very low*,k
BF Z blue light filtering; CI Z confidence interval; cryst Z crystalline; ESS Z Epworth Sleepiness Score; PSQI Z Pittsburgh Sleep Quality Index; RR Z risk ratio Poor sleepers defined by PSQI global score O5. Very low quality: Very uncertain about the estimate. *Sample size too low to meet optimum information size criterion. † Downgraded because of large dropout (9%–22% in clear IOL and blue light–filtering IOL groups, respectively) in Alexander et al.29 z Downgraded because heterogeneity 80%. x Original sample size 108; 63 completed ESS 1 month postoperatively. Not clear how many who filled out ESS at baseline also filled out ESS at follow-up. k Dropout 20% (3/15).
Table 1B. Effect of IOL type, combined scales, on regulation of circadian rhythms in nonrandomized studies.
Outcomes Sleepiness scores Sleepiness scores: ESS Sleepiness scores: PSQI Poor sleepers: BF vs clear IOL
Findings (95% CI) Mean scores 0.05 SDs higher (0.08 lower to 0.18 higher) in favor of clear IOL compared with BF IOL Mean EEB 0.07 SDs higher (0.44 lower to 0.58 higher) in favor of clear IOL compared with BF IOL Mean PSQI global score 0.05 SDs higher (0.08 lower to 0.19 higher) in favor of clear IOL compared with BF IOL RR 1.08 (0.63 to 1.84) in favor of clear IOL compared with BF IOL
Number of Participants
Quality of Evidence
929 (3 studies)
Very low*,†,z
63 (1 study)
Very low*,z
866 (2 studies)
Very low*,†
49 (1 study)
Very low*,x
BF Z blue light filtering; CI Z confidence interval; cryst Z crystalline; ESS Z Epworth Sleepiness Score; PSQI Z Pittsburgh Sleep Quality Index; RR Z risk ratio; SD Z standard deviation Poor sleepers defined by PSQI global score O5. Very low quality: Very uncertain about the estimate. *Sample size too low to meet optimum information size criterion. † Downgraded because of large dropout (9%–22% in clear IOL and blue light–filtering IOL groups, respectively) in Alexander et al.29 z Original sample size was 108; 63 completed ESS 1 month postoperatively. Not clear how many who filled out ESS at baseline also filled out ESS at follow-up. x Dropout was 20% (3/15).
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
that blue light–filtering IOLs filter approximately 20% of the blue light transmitted through clear IOLs at 480 nm.18,19 A few studies assessed the theoretical potential for photoentrainment in different IOLs. All found blue light–filtering IOLs had a lower potential for photoentrainment than clear IOLs,19,20,44 but the clinical effect of the blue light–filtering IOLs was expected to be small.19 We found no significant difference in the regulation of circadian rhythms between the 2 IOL types, which corroborates this expectation, but it does not prove there is no difference because the level of evidence was very low. We found the quality of evidence for all outcomes to be very low by evaluating study design, imprecision, inconsistency, indirectness, study limitations, risk for publication bias, magnitude of effect, dose response, and whether there were confounders likely to minimize the effect. The primary reasons for the very low grading of evidence were that all included studies were nonrandomized and too few participants were included for each outcome, even when the outcome was evaluated across included studies. Additionally, heterogeneity was substantial for the effect of cataract surgery measured by the PSQI global score and dropout was large in some included studies, which downgraded a number of outcomes (Table 1). The small number of participants in the included studies caused wide CIs, making estimates imprecise. None of the outcomes included enough participants to meet the optimum information size, which is the number of participants needed for a single study to show a difference at a certain power.54 We chose to include all studies that reported on participants with age-related cataract regardless of other study participant characteristics. Included studies differed substantially in exclusion criteria and whether they reported on first-eye, second-eye, or bilateral surgery (Appendix 1). This may have influenced the results because study populations were heterogeneous and the effect of cataract surgery on the regulation of circadian rhythms may vary depending on whether first-eye, second-eye, or bilateral surgery is performed. To our knowledge, the latter has not been investigated. The low quality of evidence is reflected in imprecise estimates, and it weakens our faith in the results. Improving sleep quality may reduce health-related and social-transfer costs and lower the risk for serious comorbidities,1–7 which benefit both patients and society. Results of the metaanalysis showed an improving effect of cataract surgery on sleep quality, but the reduction in the mean PSQI global score was less than 1 and it is not clear whether this effect was clinically relevant. Since the PSQI is skewed, a reduction of 1 in the PSQI global score is supposedly of greater effect in a patient with a low baseline score, but
2003
currently available data did not allow the investigation of a dose-response association between severities of cataract and a change in the PSQI global score or between the preoperative PSQI score and the degree of improvement after surgery. Cataract surgery is an invasive procedure and is currently not performed to improve sleep disturbances. Our findings were based on studies that included patients who were not diagnosed with sleep disturbances preoperatively. Thus, we do not have any evidence to determine whether cataract surgery will improve sleep in patients with sleep disturbances. In conclusion, this systematic review and metaanalysis showed that cataract surgery had some improving effect on regulation of circadian rhythms, but the effect was only present in 1 outcome and the strength of our conclusion was limited by the low quality of available evidence. We found no evidence favoring 1 type of IOL over the other. Participants in the studies included in the metaanalysis were not diagnosed with sleep disturbances, making it difficult to show an effect on sleep disturbances. To further investigate the effect of cataract surgery on the regulation of circadian rhythms, large randomized controlled trials are needed.
REFERENCES 1. Ancoli-Israel S. Sleep and its disorders in aging populations. Sleep Med 2009; 10(suppl 1):S7–S11 2. Blackwell T, Yaffe K, Ancoli-Israel S, Schneider JL, Cauly JA, Hillier TA, Fink HA, Stone KL; for the Study of Osteoporotic Fractures Group. Poor sleep is associated with impaired cognitive function in older women: the study of osteoporotic fractures. J Gerontol A Biol Sci Med Sci 2006; 61:405–410 3. Stone KL, Blackwell TL, Ancoli-Israel S, Cauly JA, Redline S, Marshall LM, Ensrud KE; for the Osteoporotic Fractures in Men Study Group. Sleep disturbances and risk of falls in older community-dwelling men: the outcomes of Sleep Disorders in Older Men (MrOS Sleep) Study. J Am Geriatr Soc 2014; 62:299–305 4. Blask DE. Melatonin, sleep disturbance and cancer risk. Sleep Med Rev 2009; 13:257–264 5. Foley D, Ancoli-Israel S, Britz P, Walsh J. Sleep disturbances and chronic disease in older adults; results of the 2003 National Sleep Foundation Sleep in America Survey. J Psychosom Res 2004; 56:497–502 6. Wang PS, Bohn RL, Glynn RJ, Mogun H, Avorn J. Hazardous benzodiazepine regimens in the elderly: effects of half-life, dosage, and duration on risk of hip fracture. Am J Psychiatry 2001; 158:892–898. Available at: http://ajp.psychiatryonline. org/doi/pdf/10.1176/appi.ajp.158.6.892. Accessed July 20, 2015 7. Jennum P, Ibsen R, Avlund K, Kjellberg J. Health, social and economic consequences of hypersomnia: a controlled national study from a national registry evaluating the societal effect on patients and their partners. Eur J Health Econ 2014; 15:303– 311 8. Berson DM. Strange vision: ganglion cells as circadian photoreceptors. Trends Neurosci 2003; 26:314–320
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
2004
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
9. Berson DM, Dunn FA, Takao M. Phototransduction by retinal ganglion cells that set the circadian clock. Science 2002; 295:1070–1073 10. Panda S, Nayak SK, Campo B, Walker JR, Hogenesch JB, Jegla T. Illumination of the melanopsin signaling pathway. Science 2005; 307:600–604 11. Hattar S, Liao H-W, Takao M, Berson DM, Yau K-W. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 2002; 295:1065–1070 12. Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature 2005; 437:1257–1263 13. Ponce A, Sorensen C, Takemoto L. Role of short-range protein interactions in lens opacifications. Mol Vis 2006; 12:879–884. Available at: http://www.molvis.org/molvis/v12/a99/v12a99ponce.pdf. Accessed July 20, 2015 14. Stradner A, Foffi G, Dorsaz N, Thurston G, Schurtenberger P. New insight into cataract formation – enhanced stability through mutual attraction. Phys Rev Lett 2007; 99:198103. Available at: http://arxiv.org/pdf/0708.3370.pdf. Accessed July 20, 2015 15. Takemoto L, Sorensen CM. Protein-protein interactions and lens transparency. Exp Eye Res 2008; 87:496–501 16. Bloemendal H, de Jong W, Jaenicke R, Lubsen NH, Slingsby C, Tardieu A. Ageing and vision: structure, stability and function of lens crystallins. Progr Biophys Mol Biol 2004; 86:407–485 17. Horwitz J. The function of alpha-crystallin in vision. Semin Cell Dev Biol 2000; 11:53–60 18. Kessel L, Lundeman JH, Herbst K, Andersen TV, Larsen M. Age-related changes in the transmission properties of the human lens and their relevance to circadian entrainment. J Cataract Refract Surg 2010; 36:308–312 19. Brøndsted AE, Lundeman JH, Kessel L. Short wavelength light filtering by the natural human lens and IOLs – implications for entrainment of circadian rhythm. Acta Ophthalmol 2013; 91:52–57. Available at: http://onlinelibrary.wiley.com/doi/10. 1111/j.1755-3768.2011.02291.x/pdf. Accessed July 20, 2015 20. Mainster MA. Violet and blue light blocking intraocular lenses: Photoprotection versus photoreception. Br J Ophthalmol 2006; 90:784–792. Available at: http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC1860240/pdf/784.pdf. Accessed July 20, 2015 21. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, Norris S, Falck-Ytter Y, Glasziou P, DeBeer H, Jaeschke R, €nemann HJ. GRADE Rind D, Meerpohl J, Dahm P, Schu guidelines: 1. IntroductiondGRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011; 64:383– 394 22. Martin JL, Hakim AD. Wrist actigraphy. Chest 2011; 139:1514– 1527. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3109647/pdf/101872.pdf. Accessed July 20, 2015 23. Buysse DJ, Reynolds CF III, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatric Res 1989; 28:193–213 24. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991; 14:540–545. Available at: http://epworthsleepinessscale.com/wp-content/uploads/ 2009/09/a_new_method_for_measure_daytime_sleepiness_the_ epworth_sleepiness_scale.pdf. Accessed July 20, 2015 €uchi K, Wirz-Justice A. Role of melatonin in 25. Cajochen C, Kra the regulation of human circadian rhythms and sleep. J Neuroendocrinol 2003; 15:432–437 26. Voultsios A, Kennaway DJ, Dawson D. Salivary melatonin as a circadian phase marker: validation and comparison to plasma melatonin. J Biol Rhythms 1997; 12:457–466
27. Bojkowski CJ, Arendt J, Shih MC, Markey SP. Melatonin secretion in humans assessed by measuring its metabolite, 6-sulfatoxymelatonin. Clin Chem 1987; 33:1343–1348. Available at: http://www.clinchem.org/content/33/8/1343.full.pdf. Accessed July 20, 2015 28. Bland JM, Altman DG. Transformations, means, and confidence intervals [statistical notes]. BMJ 1996; 312:1079. Available at: http://www.bmj.com/content/bmj/312/7038/1079.full. pdf. Accessed July 20, 2015 29. Alexander I, Cuthbertson FM, Ratnarajan G, Safa R, Mellington FE, Foster RG, Downes SM, Wulff K. Impact of cataract surgery on sleep in patients receiving either ultravioletblocking or blue-filtering intraocular lens implants. Invest Ophthalmol Vis Sci 2014; 55:4999–5004. Available at: http:// www.ncbi.nlm.nih.gov/pmc/articles/PMC4132556/pdf/i15525783-55-8-4999.pdf. Accessed July 20, 2015 30. Schmoll C, Khan A, Aspinall P, Goudie C, Koay P, Tendo C, Cameron J, Roe J, Deary I, Dhillon B. New light for old eyes: comparing melanopsin-mediated non-visual benefits of bluelight and UV-blocking intraocular lenses. Br J Ophthalmol 2014; 98:124–128 31. Ayaki M, Negishi K, Tsubota K. Rejuvenation effects of cataract surgery with UV blocking intra-ocular lens on circadian rhythm and gait speed. Rejuvenation Res 2014; 17:359–365 32. Ayaki M, Muramatsu M, Negishi K, Tsubota K. Improvements in sleep quality and gait speed after cataract surgery. Rejuvenation Res 2013; 16:35–42 33. Wei X, She C, Chen D, Yan F, Zeng J, Zeng L, Wang L. Blue-light-blocking intraocular lens implantation improves the sleep quality of cataract patients. J Clin Sleep Med 2013; 9:741–745. Available at: http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3716663/pdf/jcsm.9.8.741.pdf. Accessed July 20, 2015 34. Tanaka M, Hosoe K, Hamada T, Morita T. Change in sleep state of the elderly before and after cataract surgery. J Physiol Anthropol 2010; 29:219–224. Available at: https://www.jstage. jst.go.jp/article/jpa2/29/6/29_6_219/_pdf. Accessed July 20, 2015 35. Landers JA, Tamblyn D, Perriam D. Effect of a blue-lightblocking intraocular lens on the quality of sleep. J Cataract Refract Surg 2009; 35:83–88 36. Adeoti C. Disorders of the sleep-wake cycle in blindness. West Afr J Med 2010; 29:163–168. Available at: http://www.ajol.info/ index.php/wajm/article/download/68214/56300. Accessed July 20, 2015 37. Asplund R, Lindblad BE. Sleep and sleepiness 1 and 9 months after cataract surgery. Arch Gerontol Geriatr 2004; 38:69–75 38. Asplund R, Ejdervik Lindblad B. The development of sleep in persons undergoing cataract surgery. Arch Gerontol Geriatr 2002; 35:179–187 39. Burkhart K, Phelps JR. Amber lenses to block blue light and improve sleep: a randomized trial. Chronobiol Int 2009; 26:1602–1612 40. Crowley SJ, Lee C, Tseng CY, Fogg LF, Eastman CI. Combinations of bright light, scheduled dark, sunglasses, and melatonin to facilitate circadian entrainment to night shift work. J Biol Rhythms 2003; 18:513–523 41. Kessel L, Siganos G, Jørgensen T, Larsen M. Sleep disturbances are related to decreased transmission of blue light to the retina caused by lens yellowing. Sleep 2011; 34:1215– 1219. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3157663/pdf/aasm.34.9.1215.pdf. Accessed July 20, 2015
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
42. Kim YH, Jung KI, Song CH. The effect of cataract on sleep time and quality in late adulthood. Aging Clin Exp Res 2012; 24:663–668 43. Lowden A, A˚kerstedt T. Assessment of a new dynamic light regimen in a nuclear power control room without windows on quickly rotating shiftworkersdeffects on health, wakefulness, and circadian alignment: a pilot study. Chronobiol Int 2012; 29:641–649 44. Patel AS, Dacey DM. Relative effectiveness of a blue light– filtering intraocular lens for photoentrainment of the circadian rhythm. J Cataract Refract Surg 2009; 35:529–539 45. Wahnschaffe A, Haedel S, Rodenbeck A, Stoll C, Rudolph H, Kozakov R, Schoepp H, Kunz D. Out of the lab and into the bathroom: evening short-term exposure to conventional light suppresses melatonin and increases alertness perception. Int J Mol Sci 2013; 14:2573–2589. Available at: http://www. ncbi.nlm.nih.gov/pmc/articles/PMC3588003/pdf/ijms-14-02573. pdf. Accessed July 20, 2015 46. Ichikawa K; and on behalf of the CHUKYO study investigators. Changes in blood pressure and sleep duration in patients with blue light-blocking/yellow-tinted intraocular lens (CHUKYO study). Hypertens Res 2014; 37:659–664 47. Herljevic M, Middleton B, Thapan K, Skene DJ. Light-induced melatonin suppression: age-related reduction in response to short wavelength light. Exp Gerontol 2005; 40:237–242 48. Pandi-Perumal SR, Trakht I, Spence DW, Srinivasan V, Dagan Y, Cardinali DP. The roles of melatonin and light in the pathophysiology and treatment of circadian rhythm sleep disorders. Nat Clin Pract Neurol 2008; 4:436–447 49. Pandi-Perumal SR, Seils LK, Kayumov L, Ralph MR, Lowe A, Moller H, Swaab DF. Senescence, sleep, and circadian rhythms. Ageing Res Rev 2002; 1:559–604 50. Iguchi H, Kato KI, Ibayashi H. Age-dependent reduction in serum melatonin concentrations in healthy human subjects. J Clin Endocrinol Metab 1982; 55:27–29 51. Yang H, Afshari NA. The yellow intraocular lens and the natural ageing lens. Curr Opin Ophthalmol 2014; 25:40–43 52. Mainster MA, Turner PL. Blue-blocking IOLs decrease photoreception without providing significant photoprotection. Surv Ophthalmol 2010; 55:272–283 53. Davison JA, Patel AS, Cunha JP, Schwiegerling J, Muftuoglu O. Recent studies provide an updated clinical perspective on blue light-filtering IOLs. Graefes Arch Clin Exp Ophthalmol 2011; 249:957–968. Available at: http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3124647/pdf/417_2011_Article_1697.pdf. Accessed July 20, 2015 54. Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso-Coello P, Rind D, Devereaux PJ, Montori VM, Freyschuss B, Vist G, Jaeschke R, Williams JW Jr, Murad MH, Sinclair D, FalckYtter Y, Meerpohl J, Whittington C, Thorlund K, Andrews J, € nemann JH. GRADE guidelines 6. Rating the quality of Schu evidencedimprecision. J Clin Epidemiol 2011; 64:1283–1293
2005
OTHER CITED MATERIAL A. Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org. Accessed July 20, 2015 B. Cochrane Informatics & Knowledge Management Department. Review Manager (RevMan) [Computer program]. Version 5.3. Copenhagen, Netherlands, The Nordic Cochrane Centre, The Cochrane Collaboration, 2014. Available at: http://tech.cochrane.org/revman. Accessed July 20, 2015 C. Cunha JP, Paiva T, Castanheira-Dinis A, “The Eye, the Intraocular Lens and the Circadian Rhythm,” presented at the 20th Congress of the European Sleep Research Society, Lisbon, Portugal, September 2010. Abstract available at: http://registra tion.akm.ch/einsicht.php?XNABSTRACT_IDZ110841&XNSP RACHE_IDZ2&XNKONGRESS_IDZ118&XNMASKEN_IDZ 900. Accessed July 20, 2015 D. U.S. National Institutes of Health Clinical Trials. The Effect of Cataract on Photoentrainment of the Circadian Rhythm in Humans (CIRCAT). NCT01686308. Available at: https://clini caltrials.gov/ct2/show/NCT01686308. Accessed July 20, 2015 E. U.S. National Institutes of Health Clinical Trials. Influence of Blue Light Filtering Intraocular Lenses on Daytime Levels of Melatonin (BluMel). NCT00444249. Available at: https://clini caltrials.gov/ct2/show/NCT00444249. Accessed July 20, 2015 F. U.S. National Institutes of Health Clinical Trials. Evaluation of Anxiolysis and Pain Associated With Retrobulbar Eye Block for Cataract Surgery: Melatonin Versus Gabapentin. NCT01200641. Available at: https://clinicaltrials.gov/ct2/show/ NCT01200641. Accessed July 20, 2015 G. U.S. National Institutes of Health Clinical Trials. Cardiovascular Consequences of NIV Withdrawal in Patients With Myotonic Dystrophy. NCT00745238. Available at: https://clinicaltrials. gov/ct2/show/NCT00745238. Accessed July 20, 2015 H. U.S. National Institutes of Health Clinical Trials. Study of Tocilizumab to Treat Polymyalgia Rheumatica. NCT01396317. Available at: https://clinicaltrials.gov/ct2/show/NCT01396317. Accessed July 20, 2015
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
First author: Jesper H. Erichsen, BSc Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
2006
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
Appendix 1. Description of included studies. Study*
Methods
Participants
Interventions
Phacoemulsification Patients with ageAlexander29 Nonrandomized dualsite intervention study related cataract having with UVF IOL (UVB, SA60AT) or BF IOL cataract surgery in first (BF, SA60AT) eye; excluded individuals with sleep disorders, treatment with benzodiazepine and diagnosis of physical/psychiatric disorder, head injury, alcohol/drug abuse but not “other eye conditions.” Mean age 76.94 G 5.53 y Follow-up 1 and 12 mo Schmoll30 Phacoemulsification Semirandomized 63 patients having with clear IOL (Tecnis clinical trial first-/second-eye ZCB00) or BF IOL cataract surgery; (SN60WF) excluded if unable to read test display, diagnosis of Parkinson disease or dementia, intercurrent illness requiring hospitalization, previous ophthalmic history involving retinal damage. Mean age 71 y (SD not available) Follow-up 1 month Ayaki31 Nonrandomized 71 consecutive patients Phacoemulsification with clear IOL intervention trial having unilateral/ (SA60AT) bilateral cataract surgery; excluded from subsequent analysis if had major intraop or postop complications. Mean age 74.1 G 8.8 y Follow-up 2 and 7 mo postop Ayaki32 Phacoemulsification Nonrandomized 155 consecutive with BF IOL (SN60WF) intervention trial patients having unilateral/bilateral cataract surgery; excluded from subsequent analysis if had major intraop/ postop complications. Mean age 74.8 G 8.0 y Follow-up 2 and 7 mo postop
Outcomes
Notes
Mean PSQI global score: UVF group: 6.35 G 3.82 preop, 5.90 G 3.71 postop; BF group: 6.39 G 4.04 preop, 6.08 G 3.88 postop
d
ESS obtained preop and 1 month postop. ESS, BF IOL: 6.1 G 5.3 preop, 5.3 G 4.5 (n Z 23); ESS, clear IOL: 6.1 G 4.8 preop, 5.0 G 3.9 postop (n Z 40)
ESS scores not reported in publication; data obtained by e-mail from first author 7/8/2014
Number of poor sleepers (PSQIO5.5): 27/64 preop, 27/64 at 2 mo postop PSQI global score: 5.7 G 3.5 preop, 5.1 G 3.1 at 2 mo postop
Number of poor sleepers postop not reported in publication; data obtained by e-mail from first author 7/11/2014
Number of poor sleepers (PSQIO5.5): 68/154 preop, 57/142 at 2 mo postop PSQI global score: 5.6 G 3.7 preop, 5.3 G 3.6 at 2 mo postop
Number of poor sleepers postop not reported in publication; data obtained by e-mail from first author 7/11/2014
(continued on next page)
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
2007
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
Appendix 1. (Cont.) Study* Wei33
Tanaka34
Landers35
Methods
Participants
Interventions
Outcomes
Notes
PSQI global scores Bilateral cataract Number of poor 40 patients having recalculated to mean surgery by sleepers (PSQIO5): bilateral cataract G SD by reviewer phacoemulsification 30/40 preop, 13/40 at surgery; excluded if (A.E.B.): 7.8 G 3.9 with BF IOL (SN60WF) 2 mo IOL could not be preop, 4.3 G 1.8 PSQI global score: implanted during postop median 7 (IQR 3-13) surgery, there were preop, median 4 (IQR retinal/optic nerve 2-7) postop conditions that could influence light or color perception, colorblindness, unable to answer questionnaire due to confusion/dementia. Median age 74 y (IQR 70-78) Follow-up after at least 2 mo by telephone Graphs show results of Circadian rhythm Nonrandomized study 15 cataract patients (9 Cataract surgery with actigraphy and evaluated by implantation of UVF men/6 women) of patients before and salivary melatonin actigraphy and IOL (clear IOL) selected by after cataract surgery before and after salivary melatonin ophthalmologist. Only cataract surgery, but every 4 h during 24 h 12 with complete data; before and 1 mo after means G SDs obtained 3 with missing data by email from cataract surgery excluded from corresponding author analysis. 7/31/14 Mean age 70.5 G 7.2 y Actigraphy: Sleep (range 62 – 80 y) efficiency 88.6 G 4.37% Follow-up after 1 mo preop, 88.6 G 4.93% postop Melatonin: Concentration 48.59 G 44.9 pg/mL preop, 53.49 G 52.01 pg/mL postop PSQI global scores Clear IOL (SI40NB) in Patients contacted by 49 patients who had Nonrandomized 31 patients, BF IOL telephone at least 6 mo recalculated to mean bilateral cataract retrospective G SD by reviewer (SN60WF) in 18 after implantation of telephone interview on surgery; excluded if no (A.E.B.): clear IOL 6.31 patients second IOL; sleep IOL implanted during sleep quality after quality evaluated by G 2.04, BF IOL 6.63 G surgery, unable to cataract surgery 3.11 telephone interview complete using PSQI. questionnaire due to Number of poor confusion/dementia, sleepers (PSQIO5): retinal/optic nerve clear IOL 16/31, BF disorders that might IOL interfere with light 10/18 perception and/or PSQI global score: color perception, clear IOL median 6 known color (IQR 3-8), BF IOL blindness. median 6 (IQR Mean age 80 G 8.1 y 3-12) Follow-up after at least 6 mo Nonrandomized pretest/posttest experiment
BF Z blue light filtering; ESS Z Epworth Sleepiness Score; IOL Z intraocular lens; IQR Z interquartile range; PSQI Z Pittsburgh Sleep Quality Index (PSQI); UV Z ultraviolet; UVF Z ultraviolet light filtering *First author J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
2008
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
Appendix 2. Risk for bias in the included studies. Study* Alexander29
Schmoll30
Ayaki31
Ayaki32
Wei33
Bias
Authors' Judgment
Support for Judgment
Random sequence generation (selection bias)
Unclear risk
Allocation concealment (selection bias)
High risk
Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias)
High risk
Dual-site study. Patients operated on in Oxford received UVF IOL (SA60AT); those operated on in Windsor received BF IOL (SN60AT) Neither investigators nor patients masked to IOL allocation Not possible to blind patients or personnel
Unclear risk Unclear risk
Selective reporting (reporting bias) Other bias Random sequence generation (selection bias)
Low risk Unclear risk Unclear risk
Allocation concealment (selection bias)
Unclear risk
Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias)
Low risk Unclear risk High risk
Selective reporting (reporting bias)
Low risk
Other bias Random sequence generation (selection bias)
Low risk Unclear risk
Allocation concealment (selection bias)
Unclear risk
Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias)
Unclear risk Unclear risk High risk
Selective reporting (reporting bias) Other bias Random sequence generation (selection bias)
Low risk Low risk High risk
Allocation concealment (selection bias)
High risk
Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias)
High risk Unclear risk Low risk
Selective reporting (reporting bias) Other bias Random sequence generation (selection bias)
Low risk Low risk High risk
Not reported 1482 recruited, 961 completed study; in UVF IOL group, 44 patients (9%) dropped out and in BF IOL group, 100 patients (22%) dropped out before 1 month postop Not likely to have occurred None reported Patients having first-eye surgery randomized to BF or UVF IOL (n Z 37); method of randomization not described further. Participants having secondeye surgery received IOL identical to previous one (nonrandomized, n Z 26) Participants voluntarily recruited from routine cataract assessment clinics after providing informed consent Participants masked to IOL type implanted. Not possible to blind surgeons or assessors to IOL type. Not reported 108 participants recruited, 80 completed study, 63 completed ESS questionnaire at 1 mo follow-up Important outcomes could be obtained from authors but not included in publication No competing interests declared Nonrandomized trial, consecutive patients enrolled Not possible to conceal whether cataract surgery performed Not a blinded trial Not reported Authors stated all 71 patients returned for 2-mo follow-up but report sleep data (PSQI) from only 64 patients Not likely to have occurred Authors declared no conflicts of interest Nonrandomized trial, consecutive patients enrolled Not possible to conceal whether cataract surgery performed Not a blinded trial Not reported Participants participating in baseline examination also completed 2-mo follow-up Not likely to have occurred Authors declared no conflict of interests Nonrandomized trial (continued on next page)
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
2009
Appendix 2. (Cont.) Study*
Tanaka34
Landers35
Bias
Authors' Judgment
Support for Judgment
Allocation concealment (selection bias)
High risk
Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias)
High risk
Not possible to conceal whether cataract surgery performed; investigators did not tell subjects supposed relationship between IOL and sleep quality Not a blinded trial
Unclear risk Low risk
Selective reporting (reporting bias) Other bias Random sequence generation (selection bias)
Low risk Low risk High risk
Allocation concealment (selection bias)
High risk
Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias)
High risk Unclear risk Unclear risk
Selective reporting (reporting bias) Other bias Random sequence generation (selection bias) Allocation concealment (selection bias)
Low risk Low risk High risk Unclear risk
Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias)
Unclear risk
Selective reporting (reporting bias) Other bias
Low risk Low risk
Low risk Low risk
Not reported Participants in baseline examination also completed follow-up Not likely to have occurred Authors declared no conflicts of interest Patients selected by ophthalmologist: “Patients were chosen who required surgery due to eyesight less than 0.7 decimal (about 20/28 to 20/29 in feet) or who had been identified as suffering from acquired tritanopia (based on the desaturated 15hue test, Lanthony, France).” Not possible to conceal whether cataract surgery performed Neither patients nor personnel blinded Not reported 12 of the 15 patients included in statistical analyses (20% dropout) Important outcomes reported Study supported by UNIVERS foundation Not randomized trial Did not describe how clear or BF IOLs chosen for patients Not reported Questionnaire administered in blinded fashion 49 of 61 eligible patients could be contacted; all contacted patients agreed to participate Not likely to have occurred No author had financial/proprietary interest in any material or method mentioned
BF Z blue light filtering; ESS Z Epworth Sleepiness Score; IOL Z intraocular lens; PSQI Z Pittsburgh Sleep Quality Index; UVF Z ultraviolet light filtering *First author
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
Effect of cataract surgery on regulation of circadian rhythms Jesper Høiberg Erichsen, BSc, Adam E. Brøndsted, MD, Line Kessel, MD, PhD
This review looked at the effect of cataract surgery on the regulation of circadian rhythms and compared the effect of blue light–filtering and clear intraocular lenses (IOLs) on circadian rhythms. A systematic review and metaanalysis were performed, and the level of evidence was evaluated based on the principles described in the Grading of Recommendations Assessment, Development, and Evaluation system. A literature search of PubMed, Embase, and Cochrane Library databases was performed, as well as a search for unpublished trials at the U.S. National Institutes of Health Clinical Trials web site. Trials that reported the effect of cataract surgery on circadian rhythms were included. Outcomes were the Pittsburgh Sleep Quality Index (PSQI) global score, number of poor sleepers, Epworth Sleepiness Score, sleep efficiency, and mean concentration of melatonin. Cataract surgery improved regulation of circadian rhythms measured by the PSQI questionnaire, but the clinical relevance is uncertain. There was no difference between the effect of the 2 IOL types. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2015; 41:1997–2009 Q 2015 ASCRS and ESCRS Supplemental material available at www.jcrsjournal.org.
Regulation of circadian rhythms is important for maintaining a healthy life. Dysregulation of circadian rhythms may lead to sleep disturbances and increases the risk for comorbidities such as cancer, falls, cardiovascular disease, psychiatric disorders, and cognitive impairment.1–5 Sleep disorders are often treated by sleep-inducing medications that have considerable adverse effects; eg, dependency, daytime sedation, Submitted: January 8, 2015. Final revision submitted: February 7, 2015. Accepted: March 16, 2015. From the Faculty of Health and Medical Sciences (Erichsen), University of Copenhagen, Copenhagen, Department of Ophthalmology (Erichsen, Brøndsted), Glostrup Hospital, Glostrup, and Department of Ophthalmology (Kessel), Roskilde Hospital, Roskilde, Denmark. Supported by the Velux Foundation (grant 30787), Søborg, Denmark. Lene Theil Skovgaard, Department of Biostatistics, University of Copenhagen, provided advice and guidance. Corresponding author: Jesper Høiberg Erichsen, BSc, Department of Ophthalmology, Glostrup Hospital, Nordre Ringvej 57, K-2600 Glostrup, Denmark. E-mail: [email protected]. Q 2015 ASCRS and ESCRS Published by Elsevier Inc.
vertigo, and increased risk for hip fractures.6 Excessive daytime sleepiness is correlated with increased healthrelated and social-transfer costs.7 Circadian rhythms are entrained to external cues, ambient light levels being the most important. The first step in photoentrainment is stimulation of a small subset of retinal ganglion cells (intrinsically photosensitive retinal ganglion cells [ipRGCs]), which contain the photopigment melanopsin. The ipRGCs are primarily sensitive to light in the blue spectrum, with a peak at approximately 480 nm.8–10 The circadian rhythms are entrained to the solar day by axons of the ipRGCs running through the retinohypothalamic tract to the suprachiasmatic nucleus, where the main circadian rhythm is generated and melatonin release is controlled.8,11,12 Another non-image-forming function of the ipRGCs is regulation of the pupillary light reflex by projection to the olivary pretectal nucleus.8,11 In theory, the age-related yellowing of the crystalline lens can be a factor in circadian rhythm disorders. Lens yellowing is caused by changes in interactions of the major structural proteins, the crystallins, in the lens.13,14 Over time, damaged crystallins accumulate, resulting in a translucent lens with a yellow color.15–17 Cataract is the term used when visual http://dx.doi.org/10.1016/j.jcrs.2015.09.009 0886-3350
1997
1998
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
function is impaired because of a translucent and yellow lens. Studies have shown that transmission of blue light through the lens decreases as yellowing of the lens increases, limiting the amount of blue light that reaches the retina.18,19 Because blue light is essential for photoentrainment of circadian rhythms and the physiologic aging process of the crystalline lens results in reduced transmission of blue light to the retina, the question arises whether natural yellowing of the crystalline lens and/or cataract is responsible for the development of circadian rhythm disorders. Cataract is treated by removing the cataractous lens and replacing it with an intraocular lens (IOL). The IOL is usually a clear ultraviolet (UV) light–filtering IOL or a yellow blue light–filtering IOL that also blocks UV light. The main argument for using a blue light– filtering IOL is theoretical protection from phototoxic damage due to exposure of short wavelength light.20 The blue light–filtering IOL has lower transmission of blue light to the retina than the clear UV light– filtering IOL.18,19 In theory, cataract surgery could improve photoentrainment of the circadian rhythms, but there may be a difference between the effect of the 2 IOL types on regulation of circadian rhythms. The aim of this systematic review and metaanalysis was to investigate the effect of cataract surgery on the regulation of circadian rhythms and determine whether it is better to implant a blue light–filtering or a clear IOL. The level of evidence was evaluated. MATERIALS AND METHODS The systematic literature review and metaanalysis were based on the principles described in the Grading of
Recommendations Assessment, Development, and Evaluation system.21 First, the topic of the systematic review was described using the patient, intervention, comparison, and outcome approach. The effect of yellowing of the optical media of the eye on the circadian rhythms (outcome) was investigated by comparing the situation with the natural cataractous lens in place (comparison) and the situation with the cataractous lens removed and replaced by an IOL (interventiondcataract surgery). Participants were human subjects with age-related cataract (patients). Second, the effect of transmission characteristics of the IOL on circadian rhythms (outcome) was investigated by comparing patients with age-related cataract (patients) having cataract surgery with implantation of a clear UV light–filtering IOL (comparison) and patients having implantation of a yellow blue light–filtering IOL (intervention). Randomized and nonrandomized interventional studies that reported the effect of cataract surgery on circadian rhythms were included. The studies could report on firsteye surgery, second-eye surgery, or bilateral surgery. Regulation of circadian rhythms can be measured in various ways. Actigraphy is a motion-based technology in which a device is placed on the wrist of the participant for at least 1 week. This gives an objective measure of sleep/wake time.22 An easier to administer way of measuring regulation of circadian rhythms is by evaluating sleep quality using a validated questionnaire such as the Pittsburgh Sleep Quality Index (PSQI)23 or the Epworth Sleepiness Score (ESS).24 Alternatively, regulation of circadian rhythms can be assessed by measuring melatonin concentrations in blood, saliva, or urine.25–27 Studies reporting on all types of circadian rhythm measurements were included in the review. A systematic literature search was performed in the PubMed, Embase, and Cochrane Library databases using the search profile illustrated in Figure 1. The search was performed on August 7, 2014. In PubMed and Embase, results were limited to “abstract available.” A search in U.S. National Institutes of Health Clinical Trials (www.clinicaltrials.gov) was performed to identify unpublished studies. The list of references with
Figure 1. Graphic presentation of the literature search profile (PubMed, Embase, and Cochrane Library databases).
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
abstracts was reviewed by 2 reviewers independently (J.H.E., A.E.B.), and potentially relevant studies were retrieved in full-text copies and read by all 3 reviewers before a study was included or excluded. Disagreement was resolved by discussion and consensus. The risk for bias was assessed for each included study using the Cochrane risk for bias toolA in the Review Manager softwareB (version 5.3, Revman). The assessment of risk for bias included evaluation of random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. Each item was graded as “low risk for bias,” “high risk for bias,” or “unclear risk for bias.” Disagreement was resolved through discussion and consensus. Data were extracted simultaneously by the 3 authors and entered into the Revman software program.B Some articles did not provide sufficient information about the desired data; if possible, data were later obtained from the study authors via e-mail. Continuous outcome data were analyzed using the mean differences approach and dichotomous outcome data using risk ratios. Most studies used the PSQI questionnaire23 to evaluate sleep quality. Data retrieved from the PSQI are not continuous but discrete, and the distribution is skewed. Because of this, PSQI data were transformed to a logarithmic scale if presented as a median to calculate the mean and standard deviation.28 Data presented as a mean were included without transformation based on the assumption of normally distributed changes in the mean. Measurements of melatonin levels produced genuinely continuous data. The Review Manager 5 softwareB was used to calculate estimates of overall treatment effects, and random-effects models were used to calculate pooled estimates of effects. Heterogeneity was quantified by conducting the chisquare and I2 tests in Revman 5, and substantial heterogeneity was defined in concordance with Cochrane Handbook; ie, I2 more than 50% and chi-square P value less than 0.1. During cataract surgery, the natural lens is replaced by an IOL that can have different transmission characteristics. Because of this, subgroup analysis of blue light–filtering IOLs versus clear IOLs was done. Data from different sleep scales were combined using standardized mean difference.
LITERATURE SEARCH The literature search yielded 2256 references. Titles and abstracts were reviewed and potentially relevant studies identified. In addition, 1 reference was identified by other means. After duplicates were removed, a list of 22 potentially relevant studies was produced and full-text copies were retrieved (Figure 1). Of the 22 studies, 7 were included in the analysis (Appendix 1)29–35 and the remaining 15 were excluded (Appendix e1, available at http://jcrsjournal. org).18–20,36–46,C One included study35 did not provide baseline data and could not be included in the analysis of the effect of cataract surgery; it could be included in the analysis of blue light–filtering versus clear IOLs as no baseline data were needed for that. All the included studies were nonrandomized trials29,31–35 except 1 that was semirandomized.30 No randomized controlled
1999
trials that met the inclusion criteria could be identified by the literature search. The search for unpublished studies yielded 5 results,D–H of which 3 studies were not relevant to the subject of this reviewF–H and 1 was terminated because it included too few participants.E The remaining study was ongoing but could be included in an update of this review.D Three studies implanted either blue light–filtering or clear IOLs,29,30,35 3 implanted only blue light– filtering IOLs,32–34 and 1 implanted only clear IOLs.31 Three studies had the number of poor sleepers as outcome,31–33 4 had PSQI global score as outcome,29,31–33 1 had ESS as outcome,30 and 1 had actigraphy and melatonin measures as outcomes.34 Data from actigraphy were obtained as sleep efficiency, and data from melatonin measures were obtained as the mean concentration of melatonin. The follow-up period was 1 month after surgery in 3 studies,29,30,34 2 months in another 3 studies,31–33 and 6 months in the last study.35 Risk for bias in the 7 included studies is presented in Appendix 2. Effect of Cataract Surgery The effect of cataract surgery on circadian rhythms was assessed with questionnaires, actigraphy, and the measurement of melatonin.29–34 The PSQI global score was significantly improved after cataract surgery, mean difference 0.86 (95% confidence interval [CI], 1.63 to 0.10) (P Z .03). Subanalysis of IOL type showed a significant improvement in the PSQI global score after implantation of a clear IOL, mean difference 0.47 (95% CI, 0.91 to 0.03) (P Z .04); there was no significant improvement in the PSQI global score after implantation of a blue light–filtering IOL, mean difference 1.25 (95% CI, 2.78 to 0.28) (Figure 2). There was no significant change in the number of poor sleepers (PSQI global score O5) after cataract surgery, risk ratio 0.75 (95% CI, 0.48 to 1.18) (Figure 3). The ESS did not change significantly after cataract surgery, mean difference 1.01 (95% CI, 2.60 to 0.58), and neither did sleep efficiency, mean difference 0.00 (95% CI, 3.73 to 3.73), or the mean concentration of melatonin, mean difference 4.90 (95% CI, 33.98 to 43.78) (Figure 2). Blue Light–Filtering Versus Clear Intraocular Lenses Three studies compared the effect of blue light– filtering versus clear IOLs on circadian photoentrainment.29,30,35 They used different sleep scales (PSQI and ESS), so the standardized mean difference was used to calculate a pooled estimate. No significant difference in the combined sleep scale score was found between the 2 types of IOLs, standardized mean difference 0.05 (95% CI, 0.08 to 0.18). Results are presented
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
2000
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
Figure 2. Forest plot illustrating the effect of cataract surgery on continuous circadian rhythm outcomes. Sleep efficiency is presented as percentage; concentration of melatonin is presented as pg/mL (BF Z blue light–filtering; CI Z confidence interval; cryst. Z crystalline; df Z degrees of freedom; IOL Z intraocular lens; IV Z inverse variance; Random Z random effects model).
in Figure 4. One study presented data on poor sleepers.35 No significant difference between the IOLs was found, risk ratio 1.08 (95% CI, 0.63-1.84) (Figure 5).
very low. All studies were nonrandomized, the sample size for each outcome was very small, the number of participants lost to follow-up was considerable, and heterogeneity was substantial for some outcomes.
Quality of Evidence
DISCUSSION
Results of the quality assessment of the current evidence for each outcome are presented in Table 1A and 1B. The evidence for all outcomes was rated
This review investigated the effect of cataract surgery on the regulation of circadian rhythms and whether it was better to implant a blue light–filtering IOL or a
Figure 3. Forest plot illustrating the effect of cataract surgery on the number of poor sleepers defined by a PSQI global score greater than 5 (BF Z blue light–filtering; CI Z confidence interval; cryst. Z crystalline; df Z degrees of freedom; IOL Z intraocular lens; M-H Z Mantel-Haenszel; Random Z random effects model).
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
2001
Figure 4. Forest plot comparing the effect of cataract surgery with implantation of a blue light–filtering or a clear IOL on questionnairebased sleep scale scores (standardized mean difference) (BF Z blue light–filtering; CI Z confidence interval; df Z degrees of freedom; IOL Z intraocular lens; IV Z inverse variance; Random Z random effects model).
clear IOL. The level of evidence was also assessed. A systematic review and metaanalysis of 7 nonrandomized trials was done, but no randomized trials were identified. Cataract surgery was found to significantly improve subjective sleep quality as assessed by the PSQI global score, but no significant changes were found in number of poor sleepers, ESS, sleep efficiency measured by actigraphy, or total melatonin secretion. No significant differences in the PSQI global score, ESS, or number of poor sleepers were found between the 2 types of IOLs. The results support the theory that cataract surgery improves regulation of circadian rhythms. However, no evidence favoring one IOL type over the other was found. The improving effect of cataract surgery on sleep quality indicates that cataract or yellowing of the crystalline lens may impair photoentrainment of circadian rhythms. The beneficial effect of cataract surgery on sleep quality corroborates the results in previous studies, which could not be included in this metaanalysis because of study design.37,38 Other investigators have found that lens yellowing and lenticular nucleosclerosis were associated with insomnia and degradation of sleep quality.41,42 Although we found a beneficial effect of cataract surgery, our results were not as convincing as those in a retrospective study that found sleep quality to be improved in 12.0% of men and 26.3% of women 1 month after cataract surgery.38 One study reported reduced ability of short wavelength light to suppress melatonin in older women not operated on for cataract compared with younger women,47 suggesting that
yellowing of the crystalline lens and age-related decreased pupil diameter limit the amount of blue light that reaches the retina, thus reducing melatonin suppression. In theory, cataract surgery would improve suppression of melatonin during the day by allowing more blue light to reach the retina. We found no change in the mean concentration of melatonin and were therefore unable to show a beneficial effect of cataract surgery on suppression of melatonin. However, the mean concentration may hide an improvement in the fluctuation of plasma melatonin. In healthy individuals, the concentration of melatonin in plasma is low during the day and begins to rise in the evening, peaking around 3 AM and falling back to its nadir in the morning.48 The amplitudes of these fluctuations are reduced with age,49,50 and an increase in amplitude of both peak and nadir after cataract surgery may leave the mean concentration unchanged even though the patient's circadian rhythms improve. Tanaka et al.34 estimated the maximum concentration and time of maximum concentration but found no significant effect of cataract surgery. No studies reported peak-to-trough ratios. Disagreements exist about which type of IOL should be recommended for implantation after cataract surgery.51–53 Some argue that blue light–filtering IOLs are beneficial due to a supposed protection against phototoxic retinal damage53; others argue that there is no proof of such protection52 and that the reduced transmission of blue light to the retina may attenuate photoentrainment of circadian rhythms and impair scotopic vision.20,52 Transmission spectra have shown Figure 5. Forest plot comparing the effect of cataract surgery with implantation of a blue light–filtering or a clear IOL on the number of poor sleepers (PSQI O5) (BF Z blue light–filtering; CI Z confidence interval; cryst. Z crystalline; df Z degrees of freedom; IOL Z intraocular lens; M-H Z MantelHaenszel; Random Z random effects model).
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
2002
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
Table 1A. Effect of cataract surgery on regulation of circadian rhythms in nonrandomized trials.
Outcomes
Findings (95% CI)
Poor sleepers Poor sleepers: BF IOL vs cryst lens Poor sleepers: Clear IOL vs cryst lens PSQI global score PSQI global score: BF IOL vs cryst lens PSQI global score: Clear IOL vs cryst lens ESS ESS: BF IOL vs cryst lens ESS: Clear IOL vs cryst lens Sleep efficiency (%)
Melatonin (mean concentration pg/mL)
RR 0.75 (0.48 to 1.18) in favor of cataract surgery compared with cryst lens RR 0.65 (0.31 to 1.33) in favor of BF IOL compared with cryst lens RR 1 (0.67 to 1.5) in favor of clear IOL compared with cryst lens Mean score 0.86 lower (1.63 to 0.1 lower) in favor of cataract surgery compared with cryst lens Mean score 1.25 lower (2.78 lower to 0.28 higher) in favor of BF IOL compared with cryst lens Mean score 0.47 lower (0.91 to 0.03 lower) in favor of clear IOL compared with cryst lens Mean ESS 1.01 lower (2.6 lower to 0.58 higher) after cataract surgery compared with cryst lens Mean ESS 0.8 lower (3.64 lower to 2.04 higher) in favor of BF IOL compared with cryst lens Mean ESS 1.1 lower (3.02 lower to 0.82 higher) in favor of clear IOL compared with cryst lens Mean efficiency 0 higher (3.73 lower to 3.73 higher) in favor of cataract surgery compared with cryst lens Mean concentration 4.9 higher (33.98 lower to 43.78 higher) in favor of cataract surgery compared with cryst lens
Number of Participants
Quality of Evidence
504 (3 studies)
Very low*
376 (2 studies)
Very low*
128 (1 study)
Very low*
2294 (4 studies)
Very low*,†,z
1214 (3 studies)
Very low*,†,z
1080 (2 studies)
Very low*,†,z
126 (1 study)
Very low*,x
46 (1 study)
Very low*,x
80 (1 study)
Very low*,x
24 (1 study)
Very low*,k
24 (1 study)
Very low*,k
BF Z blue light filtering; CI Z confidence interval; cryst Z crystalline; ESS Z Epworth Sleepiness Score; PSQI Z Pittsburgh Sleep Quality Index; RR Z risk ratio Poor sleepers defined by PSQI global score O5. Very low quality: Very uncertain about the estimate. *Sample size too low to meet optimum information size criterion. † Downgraded because of large dropout (9%–22% in clear IOL and blue light–filtering IOL groups, respectively) in Alexander et al.29 z Downgraded because heterogeneity 80%. x Original sample size 108; 63 completed ESS 1 month postoperatively. Not clear how many who filled out ESS at baseline also filled out ESS at follow-up. k Dropout 20% (3/15).
Table 1B. Effect of IOL type, combined scales, on regulation of circadian rhythms in nonrandomized studies.
Outcomes Sleepiness scores Sleepiness scores: ESS Sleepiness scores: PSQI Poor sleepers: BF vs clear IOL
Findings (95% CI) Mean scores 0.05 SDs higher (0.08 lower to 0.18 higher) in favor of clear IOL compared with BF IOL Mean EEB 0.07 SDs higher (0.44 lower to 0.58 higher) in favor of clear IOL compared with BF IOL Mean PSQI global score 0.05 SDs higher (0.08 lower to 0.19 higher) in favor of clear IOL compared with BF IOL RR 1.08 (0.63 to 1.84) in favor of clear IOL compared with BF IOL
Number of Participants
Quality of Evidence
929 (3 studies)
Very low*,†,z
63 (1 study)
Very low*,z
866 (2 studies)
Very low*,†
49 (1 study)
Very low*,x
BF Z blue light filtering; CI Z confidence interval; cryst Z crystalline; ESS Z Epworth Sleepiness Score; PSQI Z Pittsburgh Sleep Quality Index; RR Z risk ratio; SD Z standard deviation Poor sleepers defined by PSQI global score O5. Very low quality: Very uncertain about the estimate. *Sample size too low to meet optimum information size criterion. † Downgraded because of large dropout (9%–22% in clear IOL and blue light–filtering IOL groups, respectively) in Alexander et al.29 z Original sample size was 108; 63 completed ESS 1 month postoperatively. Not clear how many who filled out ESS at baseline also filled out ESS at follow-up. x Dropout was 20% (3/15).
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
that blue light–filtering IOLs filter approximately 20% of the blue light transmitted through clear IOLs at 480 nm.18,19 A few studies assessed the theoretical potential for photoentrainment in different IOLs. All found blue light–filtering IOLs had a lower potential for photoentrainment than clear IOLs,19,20,44 but the clinical effect of the blue light–filtering IOLs was expected to be small.19 We found no significant difference in the regulation of circadian rhythms between the 2 IOL types, which corroborates this expectation, but it does not prove there is no difference because the level of evidence was very low. We found the quality of evidence for all outcomes to be very low by evaluating study design, imprecision, inconsistency, indirectness, study limitations, risk for publication bias, magnitude of effect, dose response, and whether there were confounders likely to minimize the effect. The primary reasons for the very low grading of evidence were that all included studies were nonrandomized and too few participants were included for each outcome, even when the outcome was evaluated across included studies. Additionally, heterogeneity was substantial for the effect of cataract surgery measured by the PSQI global score and dropout was large in some included studies, which downgraded a number of outcomes (Table 1). The small number of participants in the included studies caused wide CIs, making estimates imprecise. None of the outcomes included enough participants to meet the optimum information size, which is the number of participants needed for a single study to show a difference at a certain power.54 We chose to include all studies that reported on participants with age-related cataract regardless of other study participant characteristics. Included studies differed substantially in exclusion criteria and whether they reported on first-eye, second-eye, or bilateral surgery (Appendix 1). This may have influenced the results because study populations were heterogeneous and the effect of cataract surgery on the regulation of circadian rhythms may vary depending on whether first-eye, second-eye, or bilateral surgery is performed. To our knowledge, the latter has not been investigated. The low quality of evidence is reflected in imprecise estimates, and it weakens our faith in the results. Improving sleep quality may reduce health-related and social-transfer costs and lower the risk for serious comorbidities,1–7 which benefit both patients and society. Results of the metaanalysis showed an improving effect of cataract surgery on sleep quality, but the reduction in the mean PSQI global score was less than 1 and it is not clear whether this effect was clinically relevant. Since the PSQI is skewed, a reduction of 1 in the PSQI global score is supposedly of greater effect in a patient with a low baseline score, but
2003
currently available data did not allow the investigation of a dose-response association between severities of cataract and a change in the PSQI global score or between the preoperative PSQI score and the degree of improvement after surgery. Cataract surgery is an invasive procedure and is currently not performed to improve sleep disturbances. Our findings were based on studies that included patients who were not diagnosed with sleep disturbances preoperatively. Thus, we do not have any evidence to determine whether cataract surgery will improve sleep in patients with sleep disturbances. In conclusion, this systematic review and metaanalysis showed that cataract surgery had some improving effect on regulation of circadian rhythms, but the effect was only present in 1 outcome and the strength of our conclusion was limited by the low quality of available evidence. We found no evidence favoring 1 type of IOL over the other. Participants in the studies included in the metaanalysis were not diagnosed with sleep disturbances, making it difficult to show an effect on sleep disturbances. To further investigate the effect of cataract surgery on the regulation of circadian rhythms, large randomized controlled trials are needed.
REFERENCES 1. Ancoli-Israel S. Sleep and its disorders in aging populations. Sleep Med 2009; 10(suppl 1):S7–S11 2. Blackwell T, Yaffe K, Ancoli-Israel S, Schneider JL, Cauly JA, Hillier TA, Fink HA, Stone KL; for the Study of Osteoporotic Fractures Group. Poor sleep is associated with impaired cognitive function in older women: the study of osteoporotic fractures. J Gerontol A Biol Sci Med Sci 2006; 61:405–410 3. Stone KL, Blackwell TL, Ancoli-Israel S, Cauly JA, Redline S, Marshall LM, Ensrud KE; for the Osteoporotic Fractures in Men Study Group. Sleep disturbances and risk of falls in older community-dwelling men: the outcomes of Sleep Disorders in Older Men (MrOS Sleep) Study. J Am Geriatr Soc 2014; 62:299–305 4. Blask DE. Melatonin, sleep disturbance and cancer risk. Sleep Med Rev 2009; 13:257–264 5. Foley D, Ancoli-Israel S, Britz P, Walsh J. Sleep disturbances and chronic disease in older adults; results of the 2003 National Sleep Foundation Sleep in America Survey. J Psychosom Res 2004; 56:497–502 6. Wang PS, Bohn RL, Glynn RJ, Mogun H, Avorn J. Hazardous benzodiazepine regimens in the elderly: effects of half-life, dosage, and duration on risk of hip fracture. Am J Psychiatry 2001; 158:892–898. Available at: http://ajp.psychiatryonline. org/doi/pdf/10.1176/appi.ajp.158.6.892. Accessed July 20, 2015 7. Jennum P, Ibsen R, Avlund K, Kjellberg J. Health, social and economic consequences of hypersomnia: a controlled national study from a national registry evaluating the societal effect on patients and their partners. Eur J Health Econ 2014; 15:303– 311 8. Berson DM. Strange vision: ganglion cells as circadian photoreceptors. Trends Neurosci 2003; 26:314–320
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
2004
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
9. Berson DM, Dunn FA, Takao M. Phototransduction by retinal ganglion cells that set the circadian clock. Science 2002; 295:1070–1073 10. Panda S, Nayak SK, Campo B, Walker JR, Hogenesch JB, Jegla T. Illumination of the melanopsin signaling pathway. Science 2005; 307:600–604 11. Hattar S, Liao H-W, Takao M, Berson DM, Yau K-W. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 2002; 295:1065–1070 12. Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature 2005; 437:1257–1263 13. Ponce A, Sorensen C, Takemoto L. Role of short-range protein interactions in lens opacifications. Mol Vis 2006; 12:879–884. Available at: http://www.molvis.org/molvis/v12/a99/v12a99ponce.pdf. Accessed July 20, 2015 14. Stradner A, Foffi G, Dorsaz N, Thurston G, Schurtenberger P. New insight into cataract formation – enhanced stability through mutual attraction. Phys Rev Lett 2007; 99:198103. Available at: http://arxiv.org/pdf/0708.3370.pdf. Accessed July 20, 2015 15. Takemoto L, Sorensen CM. Protein-protein interactions and lens transparency. Exp Eye Res 2008; 87:496–501 16. Bloemendal H, de Jong W, Jaenicke R, Lubsen NH, Slingsby C, Tardieu A. Ageing and vision: structure, stability and function of lens crystallins. Progr Biophys Mol Biol 2004; 86:407–485 17. Horwitz J. The function of alpha-crystallin in vision. Semin Cell Dev Biol 2000; 11:53–60 18. Kessel L, Lundeman JH, Herbst K, Andersen TV, Larsen M. Age-related changes in the transmission properties of the human lens and their relevance to circadian entrainment. J Cataract Refract Surg 2010; 36:308–312 19. Brøndsted AE, Lundeman JH, Kessel L. Short wavelength light filtering by the natural human lens and IOLs – implications for entrainment of circadian rhythm. Acta Ophthalmol 2013; 91:52–57. Available at: http://onlinelibrary.wiley.com/doi/10. 1111/j.1755-3768.2011.02291.x/pdf. Accessed July 20, 2015 20. Mainster MA. Violet and blue light blocking intraocular lenses: Photoprotection versus photoreception. Br J Ophthalmol 2006; 90:784–792. Available at: http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC1860240/pdf/784.pdf. Accessed July 20, 2015 21. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, Norris S, Falck-Ytter Y, Glasziou P, DeBeer H, Jaeschke R, €nemann HJ. GRADE Rind D, Meerpohl J, Dahm P, Schu guidelines: 1. IntroductiondGRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011; 64:383– 394 22. Martin JL, Hakim AD. Wrist actigraphy. Chest 2011; 139:1514– 1527. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3109647/pdf/101872.pdf. Accessed July 20, 2015 23. Buysse DJ, Reynolds CF III, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatric Res 1989; 28:193–213 24. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991; 14:540–545. Available at: http://epworthsleepinessscale.com/wp-content/uploads/ 2009/09/a_new_method_for_measure_daytime_sleepiness_the_ epworth_sleepiness_scale.pdf. Accessed July 20, 2015 €uchi K, Wirz-Justice A. Role of melatonin in 25. Cajochen C, Kra the regulation of human circadian rhythms and sleep. J Neuroendocrinol 2003; 15:432–437 26. Voultsios A, Kennaway DJ, Dawson D. Salivary melatonin as a circadian phase marker: validation and comparison to plasma melatonin. J Biol Rhythms 1997; 12:457–466
27. Bojkowski CJ, Arendt J, Shih MC, Markey SP. Melatonin secretion in humans assessed by measuring its metabolite, 6-sulfatoxymelatonin. Clin Chem 1987; 33:1343–1348. Available at: http://www.clinchem.org/content/33/8/1343.full.pdf. Accessed July 20, 2015 28. Bland JM, Altman DG. Transformations, means, and confidence intervals [statistical notes]. BMJ 1996; 312:1079. Available at: http://www.bmj.com/content/bmj/312/7038/1079.full. pdf. Accessed July 20, 2015 29. Alexander I, Cuthbertson FM, Ratnarajan G, Safa R, Mellington FE, Foster RG, Downes SM, Wulff K. Impact of cataract surgery on sleep in patients receiving either ultravioletblocking or blue-filtering intraocular lens implants. Invest Ophthalmol Vis Sci 2014; 55:4999–5004. Available at: http:// www.ncbi.nlm.nih.gov/pmc/articles/PMC4132556/pdf/i15525783-55-8-4999.pdf. Accessed July 20, 2015 30. Schmoll C, Khan A, Aspinall P, Goudie C, Koay P, Tendo C, Cameron J, Roe J, Deary I, Dhillon B. New light for old eyes: comparing melanopsin-mediated non-visual benefits of bluelight and UV-blocking intraocular lenses. Br J Ophthalmol 2014; 98:124–128 31. Ayaki M, Negishi K, Tsubota K. Rejuvenation effects of cataract surgery with UV blocking intra-ocular lens on circadian rhythm and gait speed. Rejuvenation Res 2014; 17:359–365 32. Ayaki M, Muramatsu M, Negishi K, Tsubota K. Improvements in sleep quality and gait speed after cataract surgery. Rejuvenation Res 2013; 16:35–42 33. Wei X, She C, Chen D, Yan F, Zeng J, Zeng L, Wang L. Blue-light-blocking intraocular lens implantation improves the sleep quality of cataract patients. J Clin Sleep Med 2013; 9:741–745. Available at: http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3716663/pdf/jcsm.9.8.741.pdf. Accessed July 20, 2015 34. Tanaka M, Hosoe K, Hamada T, Morita T. Change in sleep state of the elderly before and after cataract surgery. J Physiol Anthropol 2010; 29:219–224. Available at: https://www.jstage. jst.go.jp/article/jpa2/29/6/29_6_219/_pdf. Accessed July 20, 2015 35. Landers JA, Tamblyn D, Perriam D. Effect of a blue-lightblocking intraocular lens on the quality of sleep. J Cataract Refract Surg 2009; 35:83–88 36. Adeoti C. Disorders of the sleep-wake cycle in blindness. West Afr J Med 2010; 29:163–168. Available at: http://www.ajol.info/ index.php/wajm/article/download/68214/56300. Accessed July 20, 2015 37. Asplund R, Lindblad BE. Sleep and sleepiness 1 and 9 months after cataract surgery. Arch Gerontol Geriatr 2004; 38:69–75 38. Asplund R, Ejdervik Lindblad B. The development of sleep in persons undergoing cataract surgery. Arch Gerontol Geriatr 2002; 35:179–187 39. Burkhart K, Phelps JR. Amber lenses to block blue light and improve sleep: a randomized trial. Chronobiol Int 2009; 26:1602–1612 40. Crowley SJ, Lee C, Tseng CY, Fogg LF, Eastman CI. Combinations of bright light, scheduled dark, sunglasses, and melatonin to facilitate circadian entrainment to night shift work. J Biol Rhythms 2003; 18:513–523 41. Kessel L, Siganos G, Jørgensen T, Larsen M. Sleep disturbances are related to decreased transmission of blue light to the retina caused by lens yellowing. Sleep 2011; 34:1215– 1219. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3157663/pdf/aasm.34.9.1215.pdf. Accessed July 20, 2015
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
42. Kim YH, Jung KI, Song CH. The effect of cataract on sleep time and quality in late adulthood. Aging Clin Exp Res 2012; 24:663–668 43. Lowden A, A˚kerstedt T. Assessment of a new dynamic light regimen in a nuclear power control room without windows on quickly rotating shiftworkersdeffects on health, wakefulness, and circadian alignment: a pilot study. Chronobiol Int 2012; 29:641–649 44. Patel AS, Dacey DM. Relative effectiveness of a blue light– filtering intraocular lens for photoentrainment of the circadian rhythm. J Cataract Refract Surg 2009; 35:529–539 45. Wahnschaffe A, Haedel S, Rodenbeck A, Stoll C, Rudolph H, Kozakov R, Schoepp H, Kunz D. Out of the lab and into the bathroom: evening short-term exposure to conventional light suppresses melatonin and increases alertness perception. Int J Mol Sci 2013; 14:2573–2589. Available at: http://www. ncbi.nlm.nih.gov/pmc/articles/PMC3588003/pdf/ijms-14-02573. pdf. Accessed July 20, 2015 46. Ichikawa K; and on behalf of the CHUKYO study investigators. Changes in blood pressure and sleep duration in patients with blue light-blocking/yellow-tinted intraocular lens (CHUKYO study). Hypertens Res 2014; 37:659–664 47. Herljevic M, Middleton B, Thapan K, Skene DJ. Light-induced melatonin suppression: age-related reduction in response to short wavelength light. Exp Gerontol 2005; 40:237–242 48. Pandi-Perumal SR, Trakht I, Spence DW, Srinivasan V, Dagan Y, Cardinali DP. The roles of melatonin and light in the pathophysiology and treatment of circadian rhythm sleep disorders. Nat Clin Pract Neurol 2008; 4:436–447 49. Pandi-Perumal SR, Seils LK, Kayumov L, Ralph MR, Lowe A, Moller H, Swaab DF. Senescence, sleep, and circadian rhythms. Ageing Res Rev 2002; 1:559–604 50. Iguchi H, Kato KI, Ibayashi H. Age-dependent reduction in serum melatonin concentrations in healthy human subjects. J Clin Endocrinol Metab 1982; 55:27–29 51. Yang H, Afshari NA. The yellow intraocular lens and the natural ageing lens. Curr Opin Ophthalmol 2014; 25:40–43 52. Mainster MA, Turner PL. Blue-blocking IOLs decrease photoreception without providing significant photoprotection. Surv Ophthalmol 2010; 55:272–283 53. Davison JA, Patel AS, Cunha JP, Schwiegerling J, Muftuoglu O. Recent studies provide an updated clinical perspective on blue light-filtering IOLs. Graefes Arch Clin Exp Ophthalmol 2011; 249:957–968. Available at: http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3124647/pdf/417_2011_Article_1697.pdf. Accessed July 20, 2015 54. Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso-Coello P, Rind D, Devereaux PJ, Montori VM, Freyschuss B, Vist G, Jaeschke R, Williams JW Jr, Murad MH, Sinclair D, FalckYtter Y, Meerpohl J, Whittington C, Thorlund K, Andrews J, € nemann JH. GRADE guidelines 6. Rating the quality of Schu evidencedimprecision. J Clin Epidemiol 2011; 64:1283–1293
2005
OTHER CITED MATERIAL A. Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org. Accessed July 20, 2015 B. Cochrane Informatics & Knowledge Management Department. Review Manager (RevMan) [Computer program]. Version 5.3. Copenhagen, Netherlands, The Nordic Cochrane Centre, The Cochrane Collaboration, 2014. Available at: http://tech.cochrane.org/revman. Accessed July 20, 2015 C. Cunha JP, Paiva T, Castanheira-Dinis A, “The Eye, the Intraocular Lens and the Circadian Rhythm,” presented at the 20th Congress of the European Sleep Research Society, Lisbon, Portugal, September 2010. Abstract available at: http://registra tion.akm.ch/einsicht.php?XNABSTRACT_IDZ110841&XNSP RACHE_IDZ2&XNKONGRESS_IDZ118&XNMASKEN_IDZ 900. Accessed July 20, 2015 D. U.S. National Institutes of Health Clinical Trials. The Effect of Cataract on Photoentrainment of the Circadian Rhythm in Humans (CIRCAT). NCT01686308. Available at: https://clini caltrials.gov/ct2/show/NCT01686308. Accessed July 20, 2015 E. U.S. National Institutes of Health Clinical Trials. Influence of Blue Light Filtering Intraocular Lenses on Daytime Levels of Melatonin (BluMel). NCT00444249. Available at: https://clini caltrials.gov/ct2/show/NCT00444249. Accessed July 20, 2015 F. U.S. National Institutes of Health Clinical Trials. Evaluation of Anxiolysis and Pain Associated With Retrobulbar Eye Block for Cataract Surgery: Melatonin Versus Gabapentin. NCT01200641. Available at: https://clinicaltrials.gov/ct2/show/ NCT01200641. Accessed July 20, 2015 G. U.S. National Institutes of Health Clinical Trials. Cardiovascular Consequences of NIV Withdrawal in Patients With Myotonic Dystrophy. NCT00745238. Available at: https://clinicaltrials. gov/ct2/show/NCT00745238. Accessed July 20, 2015 H. U.S. National Institutes of Health Clinical Trials. Study of Tocilizumab to Treat Polymyalgia Rheumatica. NCT01396317. Available at: https://clinicaltrials.gov/ct2/show/NCT01396317. Accessed July 20, 2015
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
First author: Jesper H. Erichsen, BSc Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
2006
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
Appendix 1. Description of included studies. Study*
Methods
Participants
Interventions
Phacoemulsification Patients with ageAlexander29 Nonrandomized dualsite intervention study related cataract having with UVF IOL (UVB, SA60AT) or BF IOL cataract surgery in first (BF, SA60AT) eye; excluded individuals with sleep disorders, treatment with benzodiazepine and diagnosis of physical/psychiatric disorder, head injury, alcohol/drug abuse but not “other eye conditions.” Mean age 76.94 G 5.53 y Follow-up 1 and 12 mo Schmoll30 Phacoemulsification Semirandomized 63 patients having with clear IOL (Tecnis clinical trial first-/second-eye ZCB00) or BF IOL cataract surgery; (SN60WF) excluded if unable to read test display, diagnosis of Parkinson disease or dementia, intercurrent illness requiring hospitalization, previous ophthalmic history involving retinal damage. Mean age 71 y (SD not available) Follow-up 1 month Ayaki31 Nonrandomized 71 consecutive patients Phacoemulsification with clear IOL intervention trial having unilateral/ (SA60AT) bilateral cataract surgery; excluded from subsequent analysis if had major intraop or postop complications. Mean age 74.1 G 8.8 y Follow-up 2 and 7 mo postop Ayaki32 Phacoemulsification Nonrandomized 155 consecutive with BF IOL (SN60WF) intervention trial patients having unilateral/bilateral cataract surgery; excluded from subsequent analysis if had major intraop/ postop complications. Mean age 74.8 G 8.0 y Follow-up 2 and 7 mo postop
Outcomes
Notes
Mean PSQI global score: UVF group: 6.35 G 3.82 preop, 5.90 G 3.71 postop; BF group: 6.39 G 4.04 preop, 6.08 G 3.88 postop
d
ESS obtained preop and 1 month postop. ESS, BF IOL: 6.1 G 5.3 preop, 5.3 G 4.5 (n Z 23); ESS, clear IOL: 6.1 G 4.8 preop, 5.0 G 3.9 postop (n Z 40)
ESS scores not reported in publication; data obtained by e-mail from first author 7/8/2014
Number of poor sleepers (PSQIO5.5): 27/64 preop, 27/64 at 2 mo postop PSQI global score: 5.7 G 3.5 preop, 5.1 G 3.1 at 2 mo postop
Number of poor sleepers postop not reported in publication; data obtained by e-mail from first author 7/11/2014
Number of poor sleepers (PSQIO5.5): 68/154 preop, 57/142 at 2 mo postop PSQI global score: 5.6 G 3.7 preop, 5.3 G 3.6 at 2 mo postop
Number of poor sleepers postop not reported in publication; data obtained by e-mail from first author 7/11/2014
(continued on next page)
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
2007
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
Appendix 1. (Cont.) Study* Wei33
Tanaka34
Landers35
Methods
Participants
Interventions
Outcomes
Notes
PSQI global scores Bilateral cataract Number of poor 40 patients having recalculated to mean surgery by sleepers (PSQIO5): bilateral cataract G SD by reviewer phacoemulsification 30/40 preop, 13/40 at surgery; excluded if (A.E.B.): 7.8 G 3.9 with BF IOL (SN60WF) 2 mo IOL could not be preop, 4.3 G 1.8 PSQI global score: implanted during postop median 7 (IQR 3-13) surgery, there were preop, median 4 (IQR retinal/optic nerve 2-7) postop conditions that could influence light or color perception, colorblindness, unable to answer questionnaire due to confusion/dementia. Median age 74 y (IQR 70-78) Follow-up after at least 2 mo by telephone Graphs show results of Circadian rhythm Nonrandomized study 15 cataract patients (9 Cataract surgery with actigraphy and evaluated by implantation of UVF men/6 women) of patients before and salivary melatonin actigraphy and IOL (clear IOL) selected by after cataract surgery before and after salivary melatonin ophthalmologist. Only cataract surgery, but every 4 h during 24 h 12 with complete data; before and 1 mo after means G SDs obtained 3 with missing data by email from cataract surgery excluded from corresponding author analysis. 7/31/14 Mean age 70.5 G 7.2 y Actigraphy: Sleep (range 62 – 80 y) efficiency 88.6 G 4.37% Follow-up after 1 mo preop, 88.6 G 4.93% postop Melatonin: Concentration 48.59 G 44.9 pg/mL preop, 53.49 G 52.01 pg/mL postop PSQI global scores Clear IOL (SI40NB) in Patients contacted by 49 patients who had Nonrandomized 31 patients, BF IOL telephone at least 6 mo recalculated to mean bilateral cataract retrospective G SD by reviewer (SN60WF) in 18 after implantation of telephone interview on surgery; excluded if no (A.E.B.): clear IOL 6.31 patients second IOL; sleep IOL implanted during sleep quality after quality evaluated by G 2.04, BF IOL 6.63 G surgery, unable to cataract surgery 3.11 telephone interview complete using PSQI. questionnaire due to Number of poor confusion/dementia, sleepers (PSQIO5): retinal/optic nerve clear IOL 16/31, BF disorders that might IOL interfere with light 10/18 perception and/or PSQI global score: color perception, clear IOL median 6 known color (IQR 3-8), BF IOL blindness. median 6 (IQR Mean age 80 G 8.1 y 3-12) Follow-up after at least 6 mo Nonrandomized pretest/posttest experiment
BF Z blue light filtering; ESS Z Epworth Sleepiness Score; IOL Z intraocular lens; IQR Z interquartile range; PSQI Z Pittsburgh Sleep Quality Index (PSQI); UV Z ultraviolet; UVF Z ultraviolet light filtering *First author J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
2008
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
Appendix 2. Risk for bias in the included studies. Study* Alexander29
Schmoll30
Ayaki31
Ayaki32
Wei33
Bias
Authors' Judgment
Support for Judgment
Random sequence generation (selection bias)
Unclear risk
Allocation concealment (selection bias)
High risk
Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias)
High risk
Dual-site study. Patients operated on in Oxford received UVF IOL (SA60AT); those operated on in Windsor received BF IOL (SN60AT) Neither investigators nor patients masked to IOL allocation Not possible to blind patients or personnel
Unclear risk Unclear risk
Selective reporting (reporting bias) Other bias Random sequence generation (selection bias)
Low risk Unclear risk Unclear risk
Allocation concealment (selection bias)
Unclear risk
Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias)
Low risk Unclear risk High risk
Selective reporting (reporting bias)
Low risk
Other bias Random sequence generation (selection bias)
Low risk Unclear risk
Allocation concealment (selection bias)
Unclear risk
Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias)
Unclear risk Unclear risk High risk
Selective reporting (reporting bias) Other bias Random sequence generation (selection bias)
Low risk Low risk High risk
Allocation concealment (selection bias)
High risk
Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias)
High risk Unclear risk Low risk
Selective reporting (reporting bias) Other bias Random sequence generation (selection bias)
Low risk Low risk High risk
Not reported 1482 recruited, 961 completed study; in UVF IOL group, 44 patients (9%) dropped out and in BF IOL group, 100 patients (22%) dropped out before 1 month postop Not likely to have occurred None reported Patients having first-eye surgery randomized to BF or UVF IOL (n Z 37); method of randomization not described further. Participants having secondeye surgery received IOL identical to previous one (nonrandomized, n Z 26) Participants voluntarily recruited from routine cataract assessment clinics after providing informed consent Participants masked to IOL type implanted. Not possible to blind surgeons or assessors to IOL type. Not reported 108 participants recruited, 80 completed study, 63 completed ESS questionnaire at 1 mo follow-up Important outcomes could be obtained from authors but not included in publication No competing interests declared Nonrandomized trial, consecutive patients enrolled Not possible to conceal whether cataract surgery performed Not a blinded trial Not reported Authors stated all 71 patients returned for 2-mo follow-up but report sleep data (PSQI) from only 64 patients Not likely to have occurred Authors declared no conflicts of interest Nonrandomized trial, consecutive patients enrolled Not possible to conceal whether cataract surgery performed Not a blinded trial Not reported Participants participating in baseline examination also completed 2-mo follow-up Not likely to have occurred Authors declared no conflict of interests Nonrandomized trial (continued on next page)
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
REVIEW/UPDATE: EFFECT OF CATARACT SURGERY ON CIRCADIAN RHYTHMS
2009
Appendix 2. (Cont.) Study*
Tanaka34
Landers35
Bias
Authors' Judgment
Support for Judgment
Allocation concealment (selection bias)
High risk
Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias)
High risk
Not possible to conceal whether cataract surgery performed; investigators did not tell subjects supposed relationship between IOL and sleep quality Not a blinded trial
Unclear risk Low risk
Selective reporting (reporting bias) Other bias Random sequence generation (selection bias)
Low risk Low risk High risk
Allocation concealment (selection bias)
High risk
Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias)
High risk Unclear risk Unclear risk
Selective reporting (reporting bias) Other bias Random sequence generation (selection bias) Allocation concealment (selection bias)
Low risk Low risk High risk Unclear risk
Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias)
Unclear risk
Selective reporting (reporting bias) Other bias
Low risk Low risk
Low risk Low risk
Not reported Participants in baseline examination also completed follow-up Not likely to have occurred Authors declared no conflicts of interest Patients selected by ophthalmologist: “Patients were chosen who required surgery due to eyesight less than 0.7 decimal (about 20/28 to 20/29 in feet) or who had been identified as suffering from acquired tritanopia (based on the desaturated 15hue test, Lanthony, France).” Not possible to conceal whether cataract surgery performed Neither patients nor personnel blinded Not reported 12 of the 15 patients included in statistical analyses (20% dropout) Important outcomes reported Study supported by UNIVERS foundation Not randomized trial Did not describe how clear or BF IOLs chosen for patients Not reported Questionnaire administered in blinded fashion 49 of 61 eligible patients could be contacted; all contacted patients agreed to participate Not likely to have occurred No author had financial/proprietary interest in any material or method mentioned
BF Z blue light filtering; ESS Z Epworth Sleepiness Score; IOL Z intraocular lens; PSQI Z Pittsburgh Sleep Quality Index; UVF Z ultraviolet light filtering *First author
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015