Health Policy Advisory Committee on Technology

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1 Health Policy Advisory Committee on Technology Technology Brief Update Femtosecond lasers for cataract surgery February 2014

2 State of Queensland (Queensland Department of Health) 2014 This work is licensed under a Creative Commons Attribution Non-Commercial No Derivatives 3.0 Australia licence. In essence, you are free to copy and communicate the work in its current form for non-commercial purposes, as long as you attribute the authors and abide by the licence terms. You may not alter or adapt the work in any way. To view a copy of this licence, visit For further information, contact the HealthPACT Secretariat at: HealthPACT Secretariat c/o Clinical Access and Redesign Unit, Health Service and Clinical Innovation Division Department of Health, Queensland Level 13, Block 7 Royal Brisbane and Women s Hospital HERSTON QLD 4029 Postal Address: GPO Box 48, Brisbane Qld HealthPACT@health.qld.gov.au Telephone: For permissions beyond the scope of this licence contact: Intellectual Property Officer, Queensland Health, GPO Box 48, Brisbane QLD 4001, ip_officer@health.qld.gov.au. Electronic copies can be obtained from: DISCLAIMER: This brief is published with the intention of providing information of interest. It is based on information available at the time of research and cannot be expected to cover any developments arising from subsequent improvements to health technologies. This brief is based on a limited literature search and is not a definitive statement on the safety, effectiveness or costeffectiveness of the health technology covered. The State of Queensland acting through Queensland Health ( Queensland Health ) does not guarantee the accuracy, currency or completeness of the information in this brief. Information may contain or summarise the views of others, and not necessarily reflect the views of Queensland Health. This brief is not intended to be used as medical advice and it is not intended to be used to diagnose, treat, cure or prevent any disease, nor should it be used for therapeutic purposes or as a substitute for a health professional's advice. It must not be relied upon without verification from authoritative sources. Queensland Health does not accept any liability, including for any injury, loss or damage, incurred by use of or reliance on the information. This brief was commissioned by Queensland Health, in its role as the Secretariat of the Health Policy Advisory Committee on Technology (HealthPACT). The production of this brief was overseen by HealthPACT. HealthPACT comprises representatives from health departments in all States and Territories, the Australian and New Zealand governments and MSAC. It is a sub-committee of the Australian Health Ministers Advisory Council (AHMAC), reporting to AHMAC s Hospitals Principal Committee (HPC). AHMAC supports HealthPACT through funding. This brief was prepared by Hong Ju from HPACT Secretariat.

3 TECHNOLOGY BRIEF UPDATE Technology, Company and Licensing Register ID Technology name Patient indication WP059 Stage of development in Australia Yet to emerge Experimental Investigational Nearly established Femtosecond lasers for cataract surgery For the removal of the crystalline lens in patients undergoing cataract surgery Established Australian Therapeutic Goods Administration approval Established but changed indication or modification of technique Should be taken out of use Yes ARTG number(s) Multiple Femtosecond ophthalmic Yb: Glass laser system were identified from TGA LenSx (Alcon Laboratories Australia Pty Ltd) Optimedica (Designs for Vision AustPty Ltd) Technolas (Emagin Pty Ltd) LensAR (IQ Medical) VICTUS (Bausch & Lomb Australia Pty Ltd) AMO (AMO Australia Pty Ltd) No Not applicable It is not entirely clear regarding the exact degree of diffusion of the technology internationally. Personal communication from one manufacturer indicates that the diffusion of femtosecond laser technology is largely confined to the private sector. According to the information provided by one manufacturer, there are a total of 22 units of different femtosecond systems in the process of being installed in Australia, all in private sector: 16 LenSX, 4 Optimedica, 1 LensAR and 1 VICTUS. In addition, two femtosecond laser systems have been installed in New Zealand (1 LenSx and 1 LensAR ). Femtosecond lasers for cataract surgery: Update February

4 International utilisation Country Level of Use Trials underway or completed Limited use Widely diffused Australia New Zealand Austria Czech Republic France Germany Hungary India Korea USA 2014 Evidence and Policy 2014 Safety and effectiveness Since the initial brief on femtosecond laser-assisted cataract surgery (FLACS), a large number of studies have been published. For the purpose of this update, only prospective comparative studies, comparing FLACS with conventional cataract surgery, with a sample size of > 100 eyes were included. However, these criteria were relaxed for Australian studies due to their relevance to local context. It is important to note that currently FLACS reflects an independent pre-treatment procedure undertaken prior to cataract surgery, which otherwise would proceed as per normal. Australian study Abell et al investigated the safety and effectiveness of FLACS using Catalys (Optimedica, Santa Clare, USA) system, compared with conventional cataract surgery, in a prospective cohort study including 400 consecutive patients in Australia (level III-2 interventional evidence). 1 Patients were excluded if aged less than 22 years, had extensive corneal scarring, corneal ring insertion, past glaucoma filtration surgery or previous refractive surgery. The laser procedure started with anterior capsulotomy followed by lens fragmentation, with surgery completed with the standard phacoemulsification procedure. Corneal incision was not performed by laser. Baseline demographic and cataract characteristics were similar between the two groups, with a mean age of 73.3 ± 9.9 years (vs 71.8 ± 10.8 years in the conventional treatment group) and mean cataract grade of 2.81 ± 0.82 (vs 2.71 ± 0.72 in the conventional group) for patients in the FLACS group. Patients were followed up at day one, day two and three weeks post-surgery. All 200 cases in the Femtosecond lasers for cataract surgery: Update February

5 FLACS group successfully completed capsulotomy, although treatment was stopped during lens fragmentation in four patients and they subsequently received conventional surgery. Intention-to-treat analysis was performed. A statistically significant reduction in mean effective phacoemulsification time (EPT) of 70 per cent (p < ) in the FLACS group (4.3 seconds) compared to the conventional group (14.3 seconds) was reported (Figure 1). Figure 1 Scatter plot of mean effective phacoemulsification time (EPT) between groups. Twenty-six patients (13%) in the FLACS group received no phacoemulsification compared to only one patient in the conventional group, and lower phacoemulsification times were observed consistently across the FLACS group (Table 1). Table 1 Number of patients with low phacoemulsification times in both groups 1 Mean EPT FLACS group N (%) Conventional group N (%) < 4 seconds 108 (54.0) 1 (0.5) < 2 seconds 70 (35.0) 1 (0.5) < 0.5 seconds 41 (20.5) 1 (0.5) < 0 seconds 26 (13.0) 1 (0.5) EPT=effective phacoemulsification time; FLACS= femtosecond laser-assisted cataract surgery The reduction was similar for all grades of cataract (results not reported). This represents a significant reduction in ultrasound energy required in the eye, with the perceived benefits of decreased post-operative complications such as corneal endothelial cell loss and cystoid macular oedema. There were no anterior capsular tags or tears in either group, and one case of posterior capsule rupture with retained nucleus in each group. No significant difference in the post-operative central macular thickness based on the optical coherence tomography (OCT) was found between the groups at one week and one month, however long-term follow up data were not available. No other direct complications of femtosecond laser treatment were reported in the study. In addition, the study also reported results on Femtosecond lasers for cataract surgery: Update February

6 femtosecond laser treatment learning curve. Compared with the initial 100 cases, a significant reduction in femtosecond vacuum time was detected in the subsequent 100 cases (3:09 ± 0:51 vs 4:09 ± 1:11 mins, p<0.0001). Bubbles on the objective lens appeared more frequent during the second 100 cases (p=0.01). Mean EPT in the second 100 cases was longer (4.75 ± 5.22 vs 3.52 ± 4.18 seconds in the initial 100 cases, p=0.067), although the difference was not statistically significant. The authors concluded that FLACS appeared to be as safe as conventional cataract surgery in the short term and resulted in significant shorter phacoemulsification time. It may provide the opportunity to further reduce the post-operative complications, however further study is needed to investigate the long term safety outcomes. Another study by the same authors compared the EPT and the associated effect on visual outcomes and endothelial cell loss in 150 cases undergoing FLACS (Catalyst, OptiMedica) and 51 cases undergoing conventional phacoemulsification (level III-2 interventional evidence). 2 All the procedures were performed by a single surgeon with prior experience with femtosecond laser platform. Similar exclusion criteria, pre- and post-operative assessments and treatments, and surgical procedures were applied as in the previous study by Abell et al. 1 There were no differences between the two groups in the demographic and other characteristics at baseline. The study did not find any significant between-group differences in mean post-operative best-corrected visual acuity, intraocular pressure (IOP), mean auto-refraction, mean absolute error of spherical equivalent at three weeks. Mean EPT was significantly shorter in the FLACS group compared with the conventional group, resulting in an 84 per cent reduction (14.24 ± vs 2.33 ± 2.28 seconds, p<0.0001, respectively) and the reduction was significant for all cataract grades (p<0.01). There were 45 (30%) cases in the FLACS group with 0 EPT compared to no case in the conventional group (p<0.0001). There were no cases of wound burn, wound leak, iris trauma or IOL decentration at one day and three weeks post-surgery, and no cases of cystoid macular oedema three weeks post-surgery in either group. However a significantly less reduction in the mean endothelial cell loss in the FLACS group ( ± 208.3) than in the conventional group ( ± ) at three weeks was detected (p=0.022). The study concluded that a significant reduction in phacoemulsification energy was possible by femtosecond laser treatment and this may lead to decreased corneal endothelial cell loss and corneal oedema in the early postoperative phase, resulting in faster visual recovery. Two additional publications from the similar group of authors also reported on the comparative safety of FLACS (Catalyst, OptiMedica) and conventional cataract surgery. One study compared the post-operative ocular inflammation using anterior chamber aqueous flare measured with laser flare photometry after FLACS (n=100) with that after conventional cataract surgery (n=76) in consecutive patients who were older than 18 years and underwent cataract surgery with insertion of a posterior chamber IOL (level III-2 Femtosecond lasers for cataract surgery: Update February

7 interventional evidence). 3 Patients were excluded if they had a pre-operative flare of more than 15 photons per millisecond (ph/ms) without pharmacological pupil dilation and a range of clinical or pathological conditions that may confound the measurements. The anterior chamber flare was measured by an investigator blinded to patient s treatment group within one week pre-operatively and one day and four weeks post-operatively. Standard treatments were given to all patients and standard surgical procedures were followed according to their assigned groups. The two groups were similar in baseline characteristics. The study found significant differences in the mean aqueous flare post-operatively both at day one (16.6 ± 8.9 vs 21.8 ± 12.0 ph/ms, p=0.0089) and four weeks (11.1 ± 8.1 vs 14.6 ± 10.7 ph/ms, p=0.003) for FLACS and conventional groups respectively (Figure 1). Similarly, a significantly shorter mean EPT was found in the FLACS group (0.94 ± 3.47 vs 6.5 ± 4.3 seconds in the conventional group, p<0.0001). There was no difference in IOP between the groups at one day post-surgery. At four weeks post-surgery, a significantly larger increase in mean outer zone retinal thickness on OCT was found in FLACS group, however no betweengroup difference in change in central macular thickness and inner zone retinal thickness from baseline was found. The authors concluded that femtosecond laser treatment resulted in reduced post-operative ocular inflammation measured by aqueous flare and a lower risk for subclinical (OCT) outer macular oedema, which appeared to be due to the reduction in phacoemulsification energy in the femtosecond group. Figure 2 Mean aqueous flare in the laser group and manual group 1 day and 4 weeks after cataract surgery (ph/ms = photons per millisecond) Another large study compared the incidence of anterior capsule tears after FLACS and phacoemulsification cataract surgery (PCS) in a prospective, multicentre study (level III-2 interventional evidence). 4 The study included 1,626 consecutive patients undergoing FLACS (n=804) or PCS (n=822), through patient self-selection, by two surgeons in two centres in Australia from April 2012 to June All patients had standard pre-operative assessments and surgical procedures according to their respective groups they were assigned to. Patients in the FLACS groups underwent laser procedures, including anterior capsulotomy and lens fragmentation, before completing with a standard phacoemulsification and an IOL Femtosecond lasers for cataract surgery: Update February

8 implementation. Baseline demographic and eye characteristics were comparable between the two groups. The study found a significantly higher incidence of anterior capsule tears in the FLACS group (1.87%, n=15) than in the PCS group (0.12%, n=1) (p=0.0002). All cases in the FLACS group occurred with complete capsulotomy and none were determined to have risk factors for capsule complications after reviewing pre-operative clinical notes. In seven patients, the anterior capsule tear extended to the posterior capsule and required sulcus IOL implantation, two of which underwent an anterior and posterior vitrectomy each due to vitreous loss. In a separate analysis, the study assessed the ultrastructural features of anterior capsulotomy specimens, using scanning electron microscopy (SEM), obtained from 50 patients (40 from FLACS and 10 from PCS group) from four centres using three different laser systems (Catalyst, LenSx and LensAR). Standard sample collection and preparation methods and imaging software were used to reduce variations and inaccurate measurements. The SEM samples from the FLACS group showed irregular capsule margin and multiple apparently misplaced laser perforations in normal parts of the tissue, which extended well inside the capsule edge. The specimens from the PCS group did not reveal any imperfection. The variations related to the different laser systems, the surgical techniques, the surgeons, and patients characteristics may all affect the architecture of the capsulotomy edge. Although the small risk of complications may be offset by the potential demonstrated improvement in surgery outcomes, further studies may be required to assess such outcomes. The authors cautioned that laser anterior capsulotomy integrity may be compromised by post-stamp perforations and additional aberrant pulses, possibly because of fixation eye movements, which may lead to an increased anterior capsule tears. International study Filkorn and colleagues conducted a small randomised controlled trial (RCT) to compare the IOL power calculation and refractive outcome between 77 eyes (77 patients) undergoing FLACS (LenSx, Alcon) and 57 eyes (57 patients) undergoing conventional cataract surgery in Hungary and Germany (level II interventional evidence). 5 Patients were excluded if they had previous ocular surgery, corneal diseases such as keratoconus, known zonular weakness, corneal astigmatism > 3.00 diopters (D), anterior capsule tear, posterior capsule rupture, severe macular disease, and amblyopia. There was no difference in baseline characteristics between the two groups. Patients in the FLACS group underwent a laser procedure including clear corneal laser incision, capsulorrhexis and cross-shaped nucleus fragmentation, prior to the phacoemulsification and implementation of an IOL. All operations were performed by a single surgeon. IOL calculation was performed with third-generation IOL formulas, and refractive outcome was measured 6-12 weeks after surgery using mean absolute error (MAE: difference between predicted and achieved postoperative spherical equivalent refraction). At 6-12 weeks after surgery, MAE was significantly lower in the FLACS group Femtosecond lasers for cataract surgery: Update February

9 compared to conventional group (a difference of D, p=0.04) after adjusting for axial length and IOL type (Table 2). However the clinical significance of the improvement is questionable. There were no significant differences in corrected distance visual acuity (CDVA) and mean error between the groups. As shown in Figure 3, significant correlation was found between IOL axial length and MAE in the conventional group (r=0.14, p=0.011), whereas no correlation was found for the FLACS group. The differences in MAE between the two groups were largest in eyes with either short (<22 mm) or long (>26 mm) axial length, both favouring the FLACS group. The study concluded that femtosecond laser cataract surgery led to significantly better predictability of IOL power calculation than conventional surgery, possibly due to a more precise capsulorrhexis resulting in a more stable IOL position. It should be noted that a couple of study authors are the consultants of the manufacturer. Table 2 Main postoperative outcomes (mean ± SD) 5 FLACS group (n=77) Conventional group (n=57) Follow-up (week) 9.72 ± ± 2.66 CDVA 0.03 ± ± 0.04 MAE (D) 0.38 ± ± 0.38 ME (D) ± ± 0.63 CDVA = corrected distance visual acuity; FLACS=femtosecond laser-assisted cataract surgery; MAE = mean absolute error; ME = mean error; SD = standard deviation Figure 3 Correlation between axial length (AL) (Lenstar LS900) and mean absolute error (MAE) following femtosecond laser refractive cataract surgery group and conventional group 5 Reddy et al conducted another small RCT to determine whether femtosecond laser-assisted lens fragmentation reduces the duration of ultrasound energy during phacoemulsification and to compare the safety of FLACS (VICTUS, Bausch & Lomb Technolas) with that of manual surgery in India (level II interventional evidence). 6 Similar but stricter exclusion criteria as Femtosecond lasers for cataract surgery: Update February

10 those in the Filkorn study 5 were applied, which included previous ocular surgery, a range of corneal diseases, disorders of ocular muscle, wound-healing disorders, autoimmune disease, and some abnormal examination results. After post-randomisation exclusion of 12 patients (8 in FLACS and 4 in conventional group) to ensure equal cataract grade distribution (no details given), 56 eyes in the FLACS group and 63 eyes in the conventional surgery group were included in the final analysis. All patients underwent standard preoperative examinations and the respective procedures, and four surgeons in a single centre performed the procedures. Patients in the FLACS group underwent a laser procedure including anterior capsulotomy and lens fragmentation of a chosen pattern (cross only, ring only, quadrant only or a combination), prior to the phacoemulsification and implementation of an IOL. The primary outcome was the EPT. Baseline demographic and eye characteristics were similar in the two groups. The study found a significantly lower mean EPT in the FLACS group (5.2 ± 5.7 vs 7.7 ± 6.0 seconds in the conventional group, p=0.025). As shown in Figure 4, the distribution of EPT differed significantly between the two groups in the lower EPT categories (p=0.001), however the mean phacoemulsification time did not differ between the groups. There was also a significant between group difference in the mean phacoemulsification energy (13.8 ± 10.3% in the FLACS vs 20.3 ± 8.1% in the conventional group, p<0.001). Only minor complications were detected at the day of surgery with significantly higher incidence of decentred capsulotomy and IOL in the conventional group (p<0.01). No adverse events were observed in either group one day post-operation. Two cases of abnormal fundus examinations were noted in the conventional group but these were deemed unrelated with the study. The authors concluded that FLACS reduced the EPT and average phacoemulsification energy and achieved precise and reproducible capsulotomy. Caution should apply to the interpretation of the study results due to the small number of patients. In addition, most authors either received travel and research grants from, or are employed by the manufacture. Figure 4 Cumulative percentage of eyes by EPT (EPT=effective phacoemulsification time) 6 In another small RCT, Conrad-Hengerer et al evaluated the impact of FLACS on endothelial cell loss and corneal thickness three months after surgery compared to conventional surgery in Germany (level II interventional evidence). 7 The study randomised each eye of each Femtosecond lasers for cataract surgery: Update February

11 patient (a total of 146 eyes in 73 patients) into either FLACS or conventional group, both with IOLs implantation. Patients were excluded if aged < 22 years, had history of serious coexistent ocular disease, uncontrolled glaucoma, optic atrophy or ocular tumours, use of topical or systemic steroids or nonsteroidal anti-inflammatory drugs during the prior three months, relevant corneal opacities, poorly dilating pupils (pupil size 6 mm), known zonular weakness. Standard pre- and post-operative management was used. Femtosecond laser treatment (Catalyst, Optimedica) was applied before phacoemulsification and IOL implementation, and all the procedures were performed by a single experienced surgeon. The two groups were similar in baseline characteristics, including Lens Opacities Classification System III (LOCS III) grades (Table 3). The study found a mean EPT of 0.0±0.1 seconds in the FLACS group and 1.4±0.1 seconds in the conventional group per cent of patients in the FLACS group had an EPF of 0 seconds compared with no patients in the conventional group. Three months postoperative, significant less endothelial cell loss (41%, p<0.001) was found in the FLACS group compared to the conventional treatment group, with a relatively high mean cell loss of 8.1 ± 8.1 and 13.7 ± 8.4 per cent in the two groups respectively. The mean relative change in corneal thickness three months from the preoperative values was 3.3 ± 1.7 per cent in the FLACS group and 3.2 ± 1.4 per cent. In addition, the study showed that both endothelial cell loss at three months (r=0.433) and CDVA one week (r=0.167) after surgery were positively correlated with the EPT. There was no intraoperative adverse event in FLACS group and one anterior capsule tear occurred in the conventional group. Postoperatively, five eyes (2 in FLACS and 3 in conventional group) developed clinically significant macular oedema with a reduction in CDVA and two eyes in conventional group developed subclinical macular oedema although all improved after treatment. The authors concluded that the FLACS did not add to endothelial cell damage caused by cataract surgery and therefore might be beneficial in eyes with preoperative low endothelial cell counts. Note that one of the authors is a member of the medical advisory board of the manufacturer. Table 3 Lens Opacities Classification System III grades and EPT by group 7 LOCS III FLACS group (n=73) Eyes (n) Conventional group (n=73) EPT (s, mean±sd) NO NO ± ±0.22 NO ± ±0.69 NO4/ ± ±1.07 FLACS=femtosecond laser-assisted cataract surgery; EPT = effective phacoemulsification time; LOCS III=Lens Opacities Classification System III; NO = nuclear opalescence Another prospective trial compared the effect of FLACS (Catalyst, OptiMedica) in 57 eyes with that of conventional cataract surgery in 52 eyes on EPT (level III-2 interventional Femtosecond lasers for cataract surgery: Update February

12 evidence). 8 Same exclusion criteria as those used in the RCT by Conrad-Hengerer et al 7 were applied to the study population. Femtosecond laser treatment was applied before phacoemulsification and IOL implementation, and all the procedures were performed by a single experienced surgeon. Patients in the FLACS group were slightly younger (median age 70 ± 11 years vs 72 ± 8 years in the conventional group) and had a tendency toward more dense cataracts (28 patients with nuclear opalescence (NO) grade 4 or higher vs 21 patients in the conventional group). Overall EPT was significantly lower in the FLACS group compared to the conventional group (0.16 ± 1.21 vs 4.07 ± 3.14 seconds respectively). Similar results were seen when EPT was compared according to preoperative LOCS III grading (Table 4). No phacoemulsification was needed in 26 per cent of the eyes in the FLACS group. No adverse intra- or postoperative events occurred and within four weeks of follow-up. The authors concluded that the use of femtosecond laser in cataract surgery led to a reduction in EPT compared to conventional surgery. Table 4 Effective phacoemulsification time (seconds) by group 8 LOCS III FLACS group (n=57) Conventional group (n=52) NO2 0.02± ±1.29 NO3 0.10± ±1.83 NO4/ ± ±3.68 FLACS=femtosecond laser-assisted cataract surgery; LOCS III=Lens Opacities Classification System III; NO=nuclear opalescence 2014 Economic evaluation Abell and Vote performed a cost-effectiveness analysis (CEA) of femtosecond laser cataract surgery (LCS) and conventional phacoemulsification cataract surgery (PCS), based on a hypothetical cohort of patients between six months and one year after surgery in Australia. 9 Complication rates and effectiveness data (visual acuity) were obtained from a systematic literature review and the authors experience using LCS, and costs were estimated from a number of sources including Medicare Benefits Scheme schedule fees, Australian Medical Association recommended fees, national hospital cost data collection reports, private health insurance company annual reports, and current industry standards. The analysis made conservative estimates on the complication rates after LCS to allow the most favourable CEA. This means if LCS fails to achieve these favourable estimates then cost effectiveness would be even worse than modelled. Visual acuity was converted to utility values based on previously used formula in the literature. In the decision model, it is assumed that 85 per cent of eyes achieved a best-corrected visual acuity (BCVA) of 6/12 after PCS (resulting in a post-cataract surgery utility of 0.978), whereas 90 per cent (a 5% improvement from PCS) of eyes achieved BCVA of 6/12 after LCS, leading to a utility of The estimated overall weighted average cost of PCS was AU$3,522 and that of LCS was AU$4,587, assuming a capital cost laser machine of Femtosecond lasers for cataract surgery: Update February

13 AU$600,000, a maintenance cost of AU$50,000 per annum with 1,000 LCS performed per annum. The result of the base-case analysis was presented in Figure 5. Compared to PCS, LCS was associated with a much higher cost and only a small incremental gain in QALY (0.06), resulting in an ICER of $92,862/QALY, which indicates that LCS is not cost-effective under current cost to patients arrangements. Figure 5 Incremental cost-effectiveness ratio (cost in Australian dollars per quality-adjusted life years) of laser cataract surgery over manual cataract surgery. LCS = laser cataract surgery; MCS = manual phacoemulsification cataract surgery; QALY = quality-adjusted life years. A series of sensitivity analyses were performed by increasing the complication rate of LCS, altering the BCVA outcomes, decreasing the expense of LCS, reducing costs to the patients, or making LCS half as effective in improving utility. The results are presented in Table 5. Keeping the complication rates unchanged and the 5 per cent increase in BCVA outcomes, reducing the cost to patient to AU$300 resulted in an ICER of AU$56,849, which is just within the cost-effectiveness threshold used in Australia. LCS was considered most costeffective when 100 per cent of patients achieved a BCVA of 6/12, cost to patient was reduced to AU$300, and LCS eliminated cystoid macular oedema, corneal decompensation and lens dislocation completely. However, it would be unlikely for LCS to currently deliver this best case scenario. Femtosecond lasers for cataract surgery: Update February

14 Table 5 Sensitivity Analysis through differing scenarios using incremental cost-effectiveness ratios in Australian dollars (AUD) per quality-adjusted life-year Scenario Visual acuity improvement (%) ICER (AUD/QALY) Baseline PCS versus no surgery NA 4,378 All complication rates differ as per model (LCS better than PCS) Base-case 5 92,862 Better case 10 58,951 Worse case Nil 218,617 LCS best case : complication rates 0% (except retinal detachment), cost to patient reduced to $ (maximum) 19,973 All complication rates equal (LCS=PCS) Base case 5 177,759 Better case 10 88,651 Complication rates differ as per model, except corneal decompensation 0% in LCS Base case 5 172,759 Better case 10 87,367 Worse case Nil 5,052,138 All complication rates differ as per model: cost to patients $300 Base case 5 56,849 Better case 10 36,089 Best case 15 25,463 ICER=incremental cost-effectiveness ratios; LCS=laser cataract surgery; PCS=phacoemulsification cataract surgery; QALY=qualityadjusted life years; The authors emphasised that the estimated safety and effectiveness data used in the decision model are relatively favourable to LCS based on available clinical data, and the cost estimates were generally conservative and based on weighted average where appropriate. Despite this, the hypothetical benefits of LCS are not considered cost-effective at its current cost to patients. Only a reduction in the capital and/or consumable costs, thus overall cost to patient, would be likely to make it more cost-effective,but still not as cost effective as current PCS techniques. Personal communication with the manufacture (Alcon) indicated the approximate current unit costs of the different systems as following: LenSx: $600,000 Optimedica: $650,000 LensAR: $450,000 (list price ~$480,000) VICTUS: $600,000 Femtosecond lasers for cataract surgery: Update February

15 Currently there is no specific MBS item number for femtosecond laser procedure. According to the cost information from the cost-effectiveness analysis, taking into account the capital cost of the laser platform and its maintenance costs (approximately $50,000 per annum), as well as the single-use disposable consumables (around $500 per eye for laser platform), the cost to patient for laser cataract surgery is currently ~$750-$1, Ongoing research A number of completed or ongoing clinical trials comparing FLACS and manual cataract surgery were identified from the ClinicalTrials.gov. The following are ongoing RCTs and costeffectiveness studies: NCT : An economic evaluation based on a RCT of femtosecond laser assisted cataract surgery (FEMCAT) in France. Primary outcome is the ICER based on outcomes 3-month after inclusion and QoL at multiple time points. The estimated study completion date is April NCT (Technolas): A multicentre RCT to addressing the efficacy and safety of femtosecond-laser assisted versus manual lens fragmentation procedure in Czech Republic and India. Primary outcome is EPT. Follow-up is 1-month postoperative. The estimated study completion date is May NCT (Technolas): A follow-up study extension to a previous RCT (NCT ) to investigate the short-term (3 months) safety of femtosecond-laser assisted cataract surgery. The estimated study completion date is July NCT (Technolas): An investigator masked RCT to investigate whether the femto-laser cataract surgery causes any significant differences in the resulting intra ocular lens overlap (ΔROverlap) in Germany. Follow-up is 6-month postoperative. The estimated study completion date is October NCT (Technolas): An investigator-masked randomised study comparing femtosecond laser assisted with conventional phacoemulsification cataract surgery in Austria. The primary outcome is EPT during surgery. The trial is not yet started recruiting and the estimated completion data is January NCT (Catalyst vs LenSx): A RCT comparing the intra-operative effects, safety, efficacy and performance of two laser systems in patients undergoing FLACS in the USA. The estimated study completion date is September Other local research (level III-2) comparative cohort studies (A/ssoc. Prof. Brendan Vote) Large multiple surgeon prospective comparative cohort study (4080 patients) analysing operative complications and EPT between LCS (n= 1852) and PCS (n=2228) submitted for publication. Femtosecond lasers for cataract surgery: Update February

16 Large multicentre prospectivecomparative cohort study (>1000 patients) assessing long term (6 months) refractive outcomes. Long term (6 months) corneal safety outcomes in prospective comparative cohort study Other issues Both Australian and international studies have indicated that FLACS technique involves a significant learning curve and initially increased complications even for the experienced cataract surgeons. Australian experience showed that a clear learning curve was reflected in the significant improvement in a range of surgery outcomes, including the number of docking attempts, miosis after the laser procedure, free-floating capsulotomies, anterior capsule tears, posterior capsule tears, posterior lens dislocation, post-laser pupillary constriction and anterior capsule tags, among the subsequent cases as compared to the initial cases. 10, 11 Surgeons prior experience with the use of femtosecond laser may help to flatten the learning curve. 10 However there is also suggestion that a significant learning curve may extend beyond the initial cases. 4 The level of uptake of the technology will ultimately be determined by further large comparative studies evaluating the clinically measurable and patient-relevant outcomes. 12 It is suggested that regulatory training bodies will need to consider the standards of the training programs across different platforms due to worldwide adoption of competencebased structure. There is also concern that the development of the laser system may result in loss of surgical skills, however it should be highlighted that a competent surgeon would be essential in managing potential complications or irregularities with the laser system and the critical factors of surgical judgement and experience cannot be simply coded into the laser system. Overall FLACS may allow less-experienced surgeons to obtain better results but may fail to demonstrate a significant improvement for experienced surgeons, thus resulting in similar outcomes across the board. The implementation of FLACS may also require significant system redesign of existing cataract surgery pathways, operating theatre space, increased staff requirement and reduced patient flow, resulting in reduced system efficiency and increased costs. 13 Significant financial costs are involved in the implementation of FLACS. Australian experience indicated that currently the investment of femtosecond laser system can only be justified, from a purely business model sense, if an institution, be it an ambulatory surgical centre, a private hospital, or a public hospital, would perform approximately 500 cataract procedures per year. 14 If the technology evolves and cost reduces, it may be applicable to smaller centres performing 200 to 300 procedures per year, however a realistic business model may prove to be difficult to develop. However these business models do not take into consideration whether the charges to patients are justifiable. Since this publication, a few Femtosecond lasers for cataract surgery: Update February

17 more femtosecond laser systems have been registered with TGA (see Australian Therapeutic Goods Administration approval section for details), however it is still too early to predict the effect of market pressures on capital and disposable costs. The evidence in favour of femtosecond laser pretreatmentremains weak (eg. short followup, small numbers, lower level evidence), thus it is unlikely to have a place in the public health system in the near future (eg. next decade). Benefits are limited when compared with current PCS techniques. Nonetheless there is likely to be group of patients (more complex cases) that will experience benefit (egpatients with compromised endothelium, mature cataracts, pseudoexfoliation). Clinician feedback indicates that, based on current evidence, this technology does not warrant either public (medicare/dva) or health insurance funding. Nonetheless it is appropriate for individual patients to choose (and self-fund) this additional procedure, and as such, neither government or insurers should create an additional financial barrier for patients choosing to accessfemtosecond laser pretreatment as part of their cataract procedure. To do so is unethical (egforcing a patient to pay for both femtosecond laser pretreatment and cataract surgery if they choose to self-fund the femtosecond laser component and otherwise would be funded for their cataract surgery eg.privately insured, DVA) Summary of findings There are a large body of controlled studies comparing FLACS to conventional cataract surgery, including a few small RCTs, being published during the last two years. Most studies showed that FLACS increased precision and reproducibility of anterior capsulotomy, significantly reduced the average effective phacoemulsification time and energy than in manual surgery, leading to a short-term reduction in postoperative corneal endothelial cell loss and decreased anterior segment inflammation in the early postoperative period. The femtosecond laser surgery is generally considered to be safe in short term, although there is some suggestion of increased anterior capsule tears. Little long-term outcomes are available. It is currently not entirely clear whether the demonstrated benefits of FLACS can be fully translate to safer, more accurate outcomes for patients as a limited number of studies have evaluated visual and refractive outcomes, with comparable outcomes being demonstrated as manual surgery. Therefore further evaluation of its effects on these patient relevant outcomes is required. At its current cost to the healthcare system and patients, the femtosecond laser cataract surgery is not considered to be cost-effective over conventional surgery in Australian context. The technology is continuously evolving and improving, with the potential to reduce the learning curve and intro- and postoperative complications related to FLACS. There are a Femtosecond lasers for cataract surgery: Update February

18 number of ongoing randomised trials and cost-effectiveness study which will provide much needed evidence on the long term and patient relevant outcomes HealthPACT assessment Femtosecond lasers produce a more precise cut and the time taken to emulsify the lens is shorter than that required by ultrasound. However, the operator is still required to be an experienced cataract surgeon and the number needed to treat with femtosecond lasers would need to be high to get a clinically significant improvement. Despite the diffusion of the technology in the private sector in Australia, limited long term, patient relevant outcomes are available and evidence of the cost-effectiveness of this procedure is lacking. Therefore it is recommended that no further research on behalf of HealthPACT is warranted at this time Included Studies All evidence included for assessment in this Technology Brief has been assessed according to the revised NHMRC levels of evidence. A document summarising these levels may be accessed via the HealthPACT web site. Total number of studies 9 Total number of Level II studies 3 Total number of Level IiI-2 studies 5 Total number of cost-effectiveness studies References 1. Abell, R. G., Kerr, N. M.&Vote, B. J. (2013). 'Femtosecond laser-assisted cataract surgery compared with conventional cataract surgery'. Clin Experiment Ophthalmol, 41 (5), Abell, R. G., Kerr, N. M.&Vote, B. J. (2013). 'Toward zero effective phacoemulsification time using femtosecond laser pretreatment'. Ophthalmology, 120 (5), Abell, R. G., Allen, P. L.&Vote, B. J. (2013). 'Anterior chamber flare after femtosecond laser-assisted cataract surgery'. J Cataract Refract Surg, 39 (9), Abell, R. G., Davies, P. E.et al (2013). 'Anterior Capsulotomy Integrity after Femtosecond Laser-Assisted Cataract Surgery'. Ophthalmology. 5. Filkorn, T., Kovacs, I.et al (2012). 'Comparison of IOL power calculation and refractive outcome after laser refractive cataract surgery with a femtosecond laser versus conventional phacoemulsification'. J Refract Surg, 28 (8), Reddy, K. P., Kandulla, J.&Auffarth, G. U. (2013). 'Effectiveness and safety of femtosecond laser-assisted lens fragmentation and anterior capsulotomy versus the manual technique in cataract surgery'. J Cataract Refract Surg, 39 (9), Conrad-Hengerer, I., Al Juburi, M.et al (2013). 'Corneal endothelial cell loss and corneal thickness in conventional compared with femtosecond laser-assisted cataract surgery: three-month follow-up'. J Cataract Refract Surg, 39 (9), Femtosecond lasers for cataract surgery: Update February

19 8. Conrad-Hengerer, I., Hengerer, F. H.et al (2012). 'Effect of femtosecond laser fragmentation on effective phacoemulsification time in cataract surgery'. J Refract Surg, 28 (12), Abell, R. G.&Vote, B. J. (2013). 'Cost-Effectiveness of Femtosecond Laser-Assisted Cataract Surgery versus Phacoemulsification Cataract Surgery'. Ophthalmology. 10. Bali, S. J., Hodge, C.et al (2012). 'Early experience with the femtosecond laser for cataract surgery'. Ophthalmology, 119 (5), Roberts, T. V., Lawless, M.et al (2013). 'Surgical outcomes and safety of femtosecond laser cataract surgery: a prospective study of 1500 consecutive cases'. Ophthalmology, 120 (2), Hodge, C., Bali, S. J.et al (2012). 'Femtosecond cataract surgery: A review of current literature and the experience from an initial installation'. Saudi J Ophthalmol, 26 (1), Trikha, S., Turnbull, A. M.et al (2013). 'The journey to femtosecond laser-assisted cataract surgery: new beginnings or a false dawn?'. Eye (Lond), 27 (4), Roberts, T. V., Lawless, M.et al (2013). 'Femtosecond laser cataract surgery: technology and clinical practice'. Clin Experiment Ophthalmol, 41 (2), Femtosecond lasers for cataract surgery: Update February

20 TECHNOLOGY BRIEF 2012 Register ID Name of Technology Purpose and Target Group WP059 (nomination from South Australia) Femtosecond lasers for cataract surgery For the removal of the crystalline lens in patients undergoing cataract surgery Stage of Development in Australia Yet to emerge Established Experimental Established but changed indication or modification of technique Investigational Should be taken out of use Nearly established Australian Therapeutic Goods Administration Approval Yes ARTG number No Not applicable International Utilisation COUNTRY Australia Hungary Germany Korea United States Trials underway or completed LEVEL OF USE Limited use Widely diffused Impact summary Although there are several ophthalmic femtosecond laser systems on the market, there is currently only one, the LenSx laser system, listed on the Australian Register of Therapeutic Goods for cataract surgery 1. The LenSx is manufactured by Alcon LenSx Inc (CA, United States) and is distributed by Alcon Laboratories Australia Pty Ltd. The technology would be made available through ophthalmic surgeons for patients who require cataract surgery. A brief describing the use of the IntraLase femtosecond laser for creating corneal flaps during laser in situ keratomileusis (LASIK) surgery was prepared by ASERNIP-S in IntraLase 1 Since writing this brief another ophthalmic femtosecond laser has been registered on the ARTG: the Designs for Vision Aust Pty Ltd - Femtosecond ophthalmic Yb: Glass laser system (ARTG number ) Femtosecond lasers for cataract surgery: February

21 was registered on the TGA (ARTG numbers and ), however, since that time IntraLase Corp has been taken over and these numbers are no longer current Worldwide and in Australia, cataracts are a common cause of vision loss and blindness. The only effective corrective measure is the surgical removal of the cataract. The use of the femtosecond laser, combined with an imaging and alignment system, enables the precise removal of the cataractous lens with reduced adverse events compared to conventional phacoemulsification procedure. In addition to cataract removal, the femtosecond laser may be used to perform a refractive lens exchange procedure Background The lens of the eye is made up primarily of protein and water and its role is to focus light onto the retina at the back of the eye (Figure 6). Cataracts are an opaque formation that develops when the protein structure of the lens breaks down and forms clumps, with the resulting cloudy appearance preventing light from passing through the lens. This opaque formation is referred to as a cataract and may occur as a result of the natural aging process, exposure to agents including x-rays, infrared or ultraviolet light, systemic disease such as diabetes, some medications, traumatic injury or the use of corticosteroids (Taylor & Bilgrami 2010). Cataracts usually progress slowly resulting in a gradual loss of vision but may eventually cause blindness if left untreated. Preventative measures such as wearing UV protecting glasses may slow the progression of cataracts, however the only effective treatment is the surgical removal of the cataract, usually by phacoemulsification (see comparator section). Figure 6 Anatomy of the eye demonstrating the position of the lens, posterior and anterior chambers (printed with permission Retina Australia, Victoria) Femtosecond lasers for cataract surgery: February

22 Complications of cataract surgery include endophthalmitis, retinal detachment and posterior capsular opacification 2 (PCO), which is reported to occur in approximately per cent of patients, two to five years after cataract surgery (Merlin et al 2011; Wormstone et al 2009). Other complications that may occur include damage to the corneal endothelium due to excessive use of ultrasound energy during the phacoemulsification of hard cataracts, thermal injury to the cornea at the site of probe insertion, in addition to iris prolapse, leakage, ocular hypotension or vision-threatening intraocular infection due to poorly constructed cataract incisions (Palanker et al 2010). In a bid to reduce the number of these complications new methods of cataract removal and wound construction have been developed and are continually evolving. LASIK has been the standard procedure for performing refractive surgical procedures for the correction of myopia, hyperopia and astigmatism. During the LASIK procedure a flap of corneal tissue is mechanically cut and folded back to allow access to the inner cornea, which is then re-shaped using an excimer laser (ASERNIP-S 2008). Complications associated with mechanical cutting led to the development of corneal procedures that utilised femtosecond lasers, which provide greater precision. The significant reduction in the number of complications during corneal refractive surgery has resulted in the wide acceptance of femtosecond lasers for LASIK procedures. The success of the LASIK procedure has stimulated interest in the use of femtosecond lasers for cataract surgery and it is envisaged that the precision of these lasers will reduce the complications such as those described above (Uy et al 2011). The main steps in laser cataract surgery are: planning, engagement, visualisation and finally, treatment. To this end, the LenSx system combines the femtosecond laser with an imaging and alignment system (Figure 7). Prior to the procedure high-resolution images are taken to produce accurate biometric measurements of the eye including the thickness of the lens and cornea (He et al 2011; Uy et al 2011). Several papers have reported the use of optical coherence tomography (OCT) for the 3-dimensional mapping of the eye, which is then linked to the femtosecond laser, which performs an anterior capsulotomy followed by fragmentation of the lens and corneal incisions (Palanker et al 2010). The femtosecond 3 laser delivers ultrashort pulses of energy at near infrared wavelengths capable of disrupting the targeted ocular tissue. 2 PCO occurs due to residual lens epithelial cells remaining on the anterior capsule, which then go on to colonise the surface of the IOL and the posterior capsule, resulting in decreased visual acuity or a secondary cataract 3 A femtosecond is of a second Femtosecond lasers for cataract surgery: February