Wet age-related macular degeneration (AMD)1 and cataract often concurrently impair visual acuity. Recent studies report a transient increase in intraretinal fluid accumulation, and hence central macular thickness, as well as exacerbation of choroidal neovascularization (CNV) after cataract surgery in patients who have wet AMD.2,3 It has been argued that the underlying mechanism for postoperative macular thickening is a breakdown of the blood–aqueous barrier resulting from surgical manipulation.4,5 In cataract surgery, tissue trauma and subsequent inflammation might be induced by the corneal incision, capsulorhexis, and lens fragmentation. However, an acceleration of wet AMD progression after cataract surgery in terms of an increased need for anti-vascular endothelial growth factor (VEGF) injections has never been shown.2,3,6
Recently, technological progress has allowed the development of an alternative surgical method in the treatment of cataract involving femtosecond-laser assistance. In comparison with conventional cataract surgery, femtosecond-laser assistance has been shown to dissect and liquefy tissue with higher precision, less collateral damage, and a comparable complication rate.7–14 Moreover, femtosecond-laser assistance has been shown to induce less anterior chamber inflammation than conventional cataract surgery.15 However to date, there is no conclusive evidence of a beneficial effect on the postoperative macular status in femtosecond laser–assisted cataract surgery.16–18 In fact, Ewe et al.17 reported that postoperative macular thickening is more pronounced after femtosecond laser–assisted cataract surgery than after conventional phacoemulsification.
To contribute to this debate, this study assessed whether patients with wet AMD benefit from femtosecond-laser assistance in terms of postoperative macular status and disease progression. More specifically, we assessed the effects on central macular thickness, central macular volume, corrected distance visual acuity (CDVA), and the number of anti-VEGF injections after femtosecond laser–assisted versus conventional cataract surgery in a retrospective case series.
Patients and Methods
This study received the approval of the relevant ethics committee (EKNZ 2015-315) and was performed according to the standards of good clinical practice. This retrospective comparative case series analyzed consecutive patients treated at the Eye Clinic of the Cantonal Hospital of Lucerne, Switzerland. All patients provided informed consent.
Using electronic patient records, patients who were treated for wet AMD by anti-VEGF injections and for cataract by surgery between January 2010 and December 2015 were identified. In regular clinical routine controls, experienced optometrists assessed the CDVA (using a logarithm of the minimum angle of resolution [logMAR] scale) as well as optical coherence tomography (OCT) measurements and documented them in electronic patient records. Retinal images and automatic follow-up horizontal 13-line raster scans with automatically measured central macular thickness, and central macular volume were obtained with OCT (Spectralis, Heidelberg Engineering GmbH). If required, demarcation lines of the inner limiting membrane and Bruch membrane were manually corrected. Demographic data, including patient age and sex, number of anti-VEGF injections, CDVA, central macular thickness, and central macular volume, were extracted by an ophthalmologic research fellow (T.J.E.).
Inclusion and Exclusion Criteria
Patients with a confirmed (by fluorescence angiography) case of wet AMD who were receiving anti-VEGF injections before cataract surgery were selected. Patients were excluded if they met 1 of the following criteria: (1) comorbid ophthalmologic diagnoses that could contribute to neovascularization, such as diabetic retinopathy or retinal vein occlusion; (2) complicated cataract surgery; (3) relevant complication resulting from anti-VEGF injections; (4) no CDVA or OCT measurements documented during the evaluation period; or (5) documented statement in an electronic patient record indicating the patient did not want to contribute personal health-related data to any study.
During the femtosecond laser–assisted cataract surgery (Catalys Precision Laser System, Abbott Medical Optics, Inc.), the anterior lens capsule was opened and the lens liquefied with a near-infrared laser. The laser light focuses at a 3 μm spot size and fires at ultrashort pulses of 10−15 seconds (femtoseconds). All patients treated with the femtosecond laser were paid out of pocket because standard coverage by the Swiss health insurers is not provided for this procedure. All included eyes had instillation of postoperative topical steroids and antibiotics as recommended in the relevant current guidelines.
Monitoring and Intravitreal Anti-Vascular Endothelial Growth Factor Therapy in Wet Age-Related Macular Degeneration
All patients included in this study were followed for their wet AMD before and after cataract surgery by the clinic’s AMD center according to a certified standard protocol. To monitor the wet AMD, patients presented for monthly clinical control visits involving continuous assessment of CDVA, OCT parameters, and clinical ophthalmic status.19,20 Criteria indicating further anti-VEGF injections therapy included intraretinal or subretinal fluid accumulation, an increase in retinal thickness of more than 20 μm, or an increase in pigment epithelium detachment size. Clinically, a newly detected macular hemorrhage was an indication of retreatment, and CDVA might have been considered in ambiguous cases. This treatment approach is called pro re nata, or as needed.
Dichotomous variates were described with percentages and continuous variates with means ± SDs. Estimates and the precision of statistical modeling were presented with means and 95% confidence intervals (CIs).
Associations between changes in central macular thickness, central macular volume, CDVA, number of anti-VEGF injections, and type of treatment were assessed with multivariate mixed linear models. These models consider that patients have provided repeated measurements during follow-up. In addition, differences were further accounted for in the distribution of parameters at baseline, entering parameters with between-group differences to the models as follows: preoperative CDVA, number of anti-VEGF injections, and exudation-free time. An indicator variate for “patient” was introduced as a random factor into statistical models to account for patients providing data for both eyes. Statistical analyses were performed using the Stata software package (version 14.1, 2015, Statacorp LLC).
Table 1 shows the patients’ characteristics. The study comprised 140 eyes of 110 patients; 123 eyes of 97 patients had conventional phacoemulsification and 17 eyes of 13 patients had femtosecond laser–assisted cataract surgery. The mean age of the patients was 80.34 ± 6.74 years. Of the 140 eyes, 100 (71.4%) were of women, of which 86 eyes had conventional phacoemulsification and 14 eyes had femtosecond laser–assisted cataract surgery (P = .395, Fisher exact test). The eyes treated with the femtosecond laser had a slightly better CDVA. The total number of anti-VEGF injections before surgery was lower in the conventional phacoemulsification group than in the femtosecond laser–assisted group (P = .008). In addition, the time between the first anti-VEGF injections and surgery was less in the conventional phacoemulsification group than in the femtosecond laser–assisted group (P = .017). These 3 parameters were used to adjust for baseline differences between the 2 treatment groups.
Patients benefited from cataract surgery in terms of the CDVA improvement and stability, independent of the surgical method (0.73 ± 0.43 logMAR versus 0.51 ± 0.38 logMAR; P < .001).
Effects of Surgical Method on Central Macular Thickness and Central Macular Volume and Visual Acuity
Multivariate statistical modeling (adjusting for preoperative CDVA, number of anti-VEGF injections, and exudation-free time) showed no significant difference in postoperative central macular thickness (−9.20 μm; 95% CI, −41.68 to 23.28; P = .576), central macular thickness (−0.08 mm2; 95% CI, −0.36 to 0.19; P = .553), and visual acuity (0.03 logMAR; 95% CI, −0.09 to 0.15; P = .647) in femtosecond laser compared with conventionally treated eyes.
However, considering the underlying mechanism of macular thickening after cataract surgery, a maximum effect was expected within the first postoperative phase. Taking this into account, an exploratory statistical analysis was performed involving only the eyes that had an OCT evaluation within a postoperative period of 2 weeks (33 eyes of 33 patients, 29 conventionally treated and 4 femtosecond laser–treated eyes). In this analysis, adjusting for the same variables mentioned above, the femtosecond laser–treated eyes had a significantly lower central macular volume (−0.71 mm2; 95% CI, −1.19 to −0.23; P = .005) than the conventionally treated eyes.
Effects of Surgical Method on Postoperative Wet Age-Related Macular Degeneration Progression
The difference between the number of postoperative anti-VEGF injections in femtosecond laser and conventionally treated eyes within 6 months was not statistically significant (2.67 ± 1.70 versus 2.71 ± 1.96) (P = .948).
This study showed that the change in central macular thickness and central macular volume as well as the increase in CDVA after cataract surgery were independent of the treatment method. Furthermore, we found an equal requirement for postoperative anti-VEGF injections in both patient groups, indicating similar progression of wet AMD after femtosecond laser–assisted and conventional cataract surgery. However, femtosecond laser–assisted cataract surgery led to less subclinical macular edema in terms of central macular volume increase within the first postoperative phase.
In 2009, Nagy et al.13 showed that phacoemulsification energy is lower in lenses that were previously liquefied by a femtosecond laser. Those preliminary findings raised hopes that femtosecond-laser assistance would lead to less effect on surrounding structures during ocular manipulation in cataract surgery. Indeed, in 2012 the same research group reported less thickening in the outer nuclear layer of the inner macular ring 4 to 8 weeks after femtosecond laser–assisted surgery versus conventional cataract surgery.14 In an analysis including only the eyes that had OCT within a postoperative period of 2 weeks, we were able to reproduce these findings in the early postoperative period. A possible explanation could be that preliquefaction of the lens might lower the need for phacoemulsification energy and thus reduce irritation of retinal structures. However, in contrast to Nagy et al., but in accordance with Yu et al.,18 we did not find effects on central macular thickness during long-term follow-up.
Several studies2,3,6 found no difference between the preoperative and postoperative number of anti-VEGF injections in conventional cataract surgery. In agreement with these previous studies, our data show that cataract surgery does not have a negative effect on the long-term outcome of anti-VEGF-treated wet AMD. It has been said that the femtosecond laser induces less anterior chamber inflammation, thereby releasing less angiogenic mediators contributing to postoperative CNV exacerbation.15 Hence, it was hoped that femtosecond laser–assisted cataract surgery might lead to a more beneficial course of postoperative wet AMD than conventional cataract surgery. However, in our study, we found no difference in the number of postoperative anti-VEGF injections between femtosecond laser–treated eyes and conventionally treated eyes. It can be argued that the course of postoperative AMD runs similarly because the 2 techniques do not differ significantly.
To our knowledge, this is the first study to explore the effects of conventional and femtosecond laser–assisted cataract surgery in patients with wet AMD. It is an asset of this study that typical cases were evaluated in real-life settings involving a mean follow-up of approximately 1.5 years.
This study is limited by the relatively small number of patients treated with femtosecond-laser assistance and its retrospective nature. Because cataract grading was not performed and phacoemulsification duration and energy were not documented routinely at the time of patient care, this information is not available. In particular, total phacoemulsification energy might influence the rate and the extent of postoperative macular edema. Also, there were significant differences in patients’ characteristics between the 2 groups. The total number of anti-VEGF injections as well as the time between the first anti-VEGF injection and cataract surgery were lower in the group with conventional treatment, indicating that in these patients, wet AMD was in a less advanced stage and therefore probably more active and perhaps more vulnerable. In addition, preoperative and postoperative OCTs were performed at different timepoints, making comparison difficult. Furthermore, we were not able to take into account systemic illnesses that are considered to influence the risk for postoperative macular edema, such as arterial hypertension or renal insufficiency.
Cataract surgery in wet AMD patients in our center, irrespective of technique used, is performed by highly experienced surgeons, which might explain why both surgical methods led to minimal structural changes. Hence, our findings might not apply for less experienced surgeons who require more time and energy for conventional phacoemulsification. A potential bias in this retrospective study could be that femtosecond-laser treatment is not generally covered by health insurance and must be paid by the patient. To what extent this introduced selection is biased is unclear. It can be argued that patients treated with the femtosecond laser might have had a higher socioeconomic level and therefore had a better general health status; however, this concept was not measured in this study.
Given the preliminary results, we believe that there is no difference between femtosecond laser–assisted and conventional cataract surgery in their effect on the long-term course of preexisting wet AMD. However, further studies will have to reproduce our findings in more sophisticated study designs to build a solid evidence base. Our study should be seen as the first step in evaluations to clarify to what extent patients with a decreased macular function might benefit from optimized cataract treatment. In future research, the clinical relevance of postoperative course of central macular thickness and central macular volume must be established.
In our study, we found that femtosecond laser–assisted surgery led to less subclinical macular edema in preexisting wet AMD in the early postoperative period. The difference was small, yet significant. It appears plausible that in diseases associated with even more compromised macular physiology, such as diabetic retinopathy or retinal vein occlusion, the differences in postoperative changes in macular morphology between femtosecond laser–assisted and conventional cataract surgery might be distinct enough to become clinically manifest. Thus, further studies might also evaluate the effects of different surgical methods in cataract treatment in other diseases that cause macular vulnerability.
In conclusion, to our knowledge this is the first study to evaluate postoperative central macular thickness, central macular volume, CDVA, and a requirement for postoperative anti-VEGF injections after femtosecond laser–assisted and conventional cataract surgery in patients with wet AMD. The results of this exploratory study indicate that there is no difference between femtosecond laser–assisted and conventional cataract surgery in their effect on the long-term course of preexisting wet AMD. Given the finding that femtosecond laser–assisted surgery had less of an effect on the early postoperative central macular volume than phacoemulsification, it appears plausible that it is beneficial for patients who have diseases that cause very high macular vulnerability.
What Was Known
- Recent studies report subclinical vulnerability for transient macular thickening and exacerbation of CNV after cataract surgery in patients who have wet AMD.
- Surgery with femtosecond-laser assistance might be a less harmful surgical method than conventional phacoemulsification in the treatment of cataract in these patients.
What This Paper Adds
- A change in central macular thickness, a change in central macular volume, an increase in CDVA, and the requirement for postoperative anti-VEGF injections after cataract surgery was independent of the treatment method.
- Femtosecond laser–assisted cataract surgery led to less subclinical macular edema than phacoemulsification in terms of central macular volume increase within the first postoperative phase; therefore, it might be beneficial for patients who have diseases that cause high macular vulnerability.
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None of the authors has a financial or proprietary interest in any material or method mentioned.